Identification and characterization of human beta 2-chimaerin: association with malignant transformation in astrocytoma.

Molecular processes resulting in the malignant transformation from low- to high-grade astrocytoma remain poorly understood. Using reverse transcriptase PCR, we identified a gene that is differentially expressed in normal brain and low-grade astrocytoma compared to glioblastoma tissues. This gene is identical to human beta 2-chimaerin, which encodes a 468-amino acid GTPase-activating protein for p21rac. The gene was localized to human chromosome 7p15.3 by fluorescence in situ hybridization mapping. Human beta 2-chimaerin is expressed in a variety of human tissues, with the highest expression level detected in human brain and pancreas. RNase protection assays indicated that the expression level of this gene is high in all the normal brain and low-grade astrocytoma samples tested compared to malignant gliomas. The down-regulation of beta 2-chimaerin expression in the high-grade gliomas suggests that decreased expression of this gene may be a feature of progression in the development of malignant glioma.

Anion influence on the binding of divalent cations to phosphatidylcholine.

We have used the osmotic pressure technique of Rand, Parsegian and co-workers (Nature 259 (1976) 601-603) to investigate the effect of anion species on the binding of M2+ to dipalmitoylphosphatidylcholine bilayers. Calcium and magnesium salts show a complex behavior which is consistent with both anion binding and screening. We observe virtually no change, within the accuracy of our experiment, in the decay of repulsive pressure with inter-bilayer separation for the acetate and nitrate salts of magnesium and calcium; however, the chloride salt does show a different pressure decay. At any given bilayer separation, 35 A less than dw less than 75 A, with calcium and magnesium salts present, the anions produce a decrease in the repulsive pressure in the order acetate- greater than Cl- greater than NO-3.

Melanotic neuroectodermal tumors of the brain and skull.

A case of melanotic neuroectodermal tumor in the cerebellum of a 21-year-old man is presented. Melanin was found mainly in small neoplastic cells rather than in large epithelioid cells. The tumor also contained neurons, as well as neoplastic tissue of ependyma, choroid plexus; and astrocytes. We propose that this neuroectodermal tumor resulted from a combination of cells originating in the neural crest and in the neural tube. The small cells have been described as medulloblasts, but they may be poorly differentiated ependymal cells, or, sympathicoblasts. The presence of pigment in these cells is compatible with an origin in the neural crest. The so-called melanotic progonoma, occurring most often in the maxilla of infants, is reviewed in relation to the melanotic neuroectodermal tumor of the brain. The tumor in facial bone occurs in adults as well as infants, in locations other than the maxilla, and has malignant forms. Melanotic neuroectodermal tumors, whether in brain or bone, are therefore similar in behavior as well as histologic appearance. The finding of similar tumors in these different locations is readily explained embryologically.

Pigmented ganglioneuroblastoma: relation of melanin and lipofuscin to schwannomas and other tumors of neural crest origin.

An unusual case of ganglioneuroblastoma containing melanin is presented. Electron microscopy revealed various stages of development of melanosomes in neoplastic cells of Schwann, the first direct demonstration in human material that these cells are malanogenic. The frequent occurrence of neuromelanin in autonomic ganglia and in ganglioneuromas is interpreted as the presence of altered lipofuscin. Review of ultrastructural and other observations indicates a relation between various pigmented tumors, the cell of Schwann, and other cells arising from the neural crest.

Muteness of cerebellar origin.

Acute bilateral damage to large areas of both cerebellar hemispheres including the dentate nuclei led to temporary loss of speech in six children. In each case muteness was unassociated with motor paralysis, loss of higher cognitive functions, or cranial nerve dysfunction. Muteness lasted one to three months. All patients were severely dysarthric during recovery. We conclude that transient muteness may result from acute bilateral cerebellar injury.

Magnetic resonance imaging (1.5 tesla) in patients with intractable focal seizures.

Magnetic resonance (MR) (1.5 tesla) studies were performed in ten patients with temporal lobe epilepsy and two with temporofrontal epilepsy. Two patients with temporal lobe epilepsy and one with temporofrontal epilepsy exhibited areas of increased signal intensity on T2-weighted images in the mesiobasal portion of the temporal lobe shown by electroencephalography to be the epileptogenic focus; no analogous abnormalities had been found in these patients on computed tomographic scans. Pathologic studies have not revealed a specific ultrastructural correlate for the MR findings in this group of patients. We found MR to be a useful, noninvasive diagnostic adjunct in the presurgical assessment of some patients with temporal lobe epilepsy. Where abnormalities were found, they corresponded with the epileptogenic focus as defined by electroencephalography.

Complications of invasive video-EEG monitoring with subdural grid electrodes.

OBJECTIVE: To evaluate the risk factors, type, and frequency of complications during video-EEG monitoring with subdural grid electrodes. METHODS: The authors retrospectively reviewed the records of all patients who underwent invasive monitoring with subdural grid electrodes (n = 198 monitoring sessions on 187 patients; median age: 24 years; range: 1 to 50 years) at the Cleveland Clinic Foundation from 1980 to 1997. RESULTS: From 1980 to 1997, the complication rate decreased (p = 0.003). In the last 5 years, 19/99 patients (19%) had complications, including two patients (2%) with permanent sequelae. In the last 3 years, the complication rate was 13.5% (n = 5/37) without permanent deficits. Overall, complications occurred during 52 monitoring sessions (26.3%): infection (n = 24; 12.1%), transient neurologic deficit (n = 22; 11.1%), epidural hematoma (n = 5; 2.5%), increased intracranial pressure (n = 5; 2.5%), and infarction (n = 3; 1.5%). One patient (0.5%) died during grid insertion. Complication occurrence was associated with greater number of grids/electrodes (p = 0.021/p = 0.052; especially >60 electrodes), longer duration of monitoring (p = 0.004; especially >10 days), older age of the patient (p = 0.005), left-sided grid insertion (p = 0.01), and burr holes in addition to the craniotomy (p = 0.022). No association with complications was found for number of seizures, IQ, anticonvulsants, or grid localization. CONCLUSIONS: Invasive monitoring with grid electrodes was associated with significant complications. Most of them were transient. Increased complication rates were related to left-sided grid insertion and longer monitoring with a greater number of electrodes (especially more than 60 electrodes). Improvements in grid technology, surgical technique, and postoperative care resulted in significant reductions in the complication rate.

Enhanced DNA synthesis of human glial cells exposed to human leukocyte products.

DNA synthesis was studied in primary glial cell cultures derived from adult human non-neoplastic and neoplastic brain tissues. Enhanced DNA synthesis occurred in 5/5 non-neoplastic astrocyte, one oligodendroglioma, and 2/5 astrocytoma cultures after exposure to medium containing 1.25-12.5% supernatant fluid (SF) from insoluble concanavalin A (Con A) stimulated unseparated or T lymphocyte-enriched human mononuclear leukocytes (MNL). Analyses of SF indicated that the presence of platelet-derived growth factor (PDGF) could not account for glial cell stimulation, and exposure to semi-purified interleukin-2 (IL-2) in amounts comparable to those in SF from Con A-stimulated MNL had no effect on glial cells. These data indicate that non-neoplastic astrocytes and other human glial cells are stimulated by products of human MNL.

Viable neurons with luxury perfusion in hydrocephalus.

A woman with hydrocephalus due to aqueductal stenosis had functional imaging of cerebral perfusion and metabolism to demonstrate the effects of endoscopic third ventriculostomy--a new form of internal surgical shunting. Technetium-99m-ECD SPECT and 18F-FDG PET showed regional luxury perfusion at the left frontal region. Three months after a successful third ventriculostomy, a repeated imaging of cerebral perfusion and metabolism showed resolution of luxury perfusion and global improvement of both perfusion and metabolism. This concurred with postoperative clinical improvement. The paired imaging of cerebral perfusion and metabolism provides more information than just imaging perfusion or metabolism. Thus, the detection of perfusion and metabolism mismatch may open a new window of opportunity for surgical intervention.

Manual vs robotically assisted laparoscopic surgery in the performance of basic manipulation and suturing tasks.

OBJECTIVE: To compare the surgical performance of manual and robotically assisted laparoscopic instruments on basic maneuvers and intracorporeal suturing in inanimate models. DESIGN: A set of laparoscopic tasks was used to evaluate basic endoscopic movements and intracorporeal suturing: positioning a cylinder on a Peg-Board, dropping beads into receptacles, running a 25-cm rope, and capping a hypodermic needle. Intracorporeal knot tying and running a suture through predetermined points were evaluated separately. The sutures used for these tasks were 2-0 and 4-0 silk and 6-0 and 7-0 polypropylene. PARTICIPANTS: Twenty surgeons completed the set of laparoscopic tasks manually and then with a robotically assisted system. None had used the robotic system before. MAIN OUTCOME MEASURES: Time required to complete the tasks and the precision in performing them. RESULTS: The robotic system accurately reproduced the movements of the surgeons and filtered their hand tremors efficiently. In the basic tasks, operative times were significantly longer for the robotic system (P<.001). In the suturing tasks, operative times were longer with the use of the robotic system for sutures sizes 2-0 and 4-0 (P<.001). However, time differences were not significant for suture sizes 6-0 and 7-0 (P> or =.07). Precision measurements were similar for all tasks using the manual instruments and the robotically assisted system. No significant differences were found between the performance of advanced laparoscopic surgeons and laparoscopic fellows. CONCLUSIONS: Laparoscopic maneuvering and suturing is faster and just as precise when performed manually as when performed with the prototype robotic system. These differences in speed are inversely proportional to the size of the suture. Future generations of the robotic system may eliminate these differences.

Pituitary apoplexy: a complication of cardiac surgery.

Pituitary apoplexy occurred in 3 patients in the immediate postoperative period following cardiac operation with cardiopulmonary bypass. In this setting, this complication is extremely rare and not widely recognized. Precipitating factors may be related to the extracorporeal bypass apparatus, anticoagulation, low cerebral blood flow, and even anesthetic agents. Neurosurgical decompression can be safely performed in the early postoperative period following open-heart operations.

Carcinoembryonic antigen in a metastatic brain tumor.

A case is presented in which 10 ml of cystic fluid from a metastatic brain tumor contained a high concentration of carcinoembryonic antigen (CEA). The use of CEA as a prognostic indicator and adjunctive therapeutic monitor in tumors is reviewed.

Delayed facial nerve palsy after temporal lobectomy for epilepsy: report of four cases and discussion of possible mechanisms.

Four cases of idiopathic peripheral facial nerve palsy were documented after 110 consecutive resections of the temporal lobe for intractable epilepsy. In 3 of the 4 cases, the palsy was ipsilateral to the side of the temporal lobectomy. The onset of facial weakness was delayed 7 to 13 days after surgery (mean, 9.7 days). One patient underwent facial electroneurography, which documented 17% of normal facial motor function at the height of his weakness and the absence of the acoustic stapedius reflex. All patients were treated with prednisone (60-80 mg per day by mouth for 10-14 days, tapering off throughout the subsequent week). Facial function recovered fully in all patients within 6 to 8 weeks. Possible mechanisms are discussed, including heat and/or mechanical trauma to the facial nerve near the geniculate ganglion during resection of mesial temporal lobe structures.

Normal pressure hydrocephalus in children and young adults.

Normal pressure hydrocephalus (NPH) is generally considered to be a disorder of adult and geriatric patients. We report four patients who are children or young adults with chronic neurological disorders, recent deterioration of their levels of function, normal cerebrospinal fluid (CSF) pressures, and ventricular enlargement. All four patients improved after the placement or revision of a ventriculoperitoneal shunt. Frequent symptoms and signs included irritability (three patients), vomiting (three patients), and abnormal limb posturing (two patients). Correct diagnosis was hampered by two factors: (a) Multiple or prolonged recordings of CSF pressures were invariably well within the normal ranges with respect to age, and (b) the patients had chronic neurological deficits. After ventriculoperitoneal shunting, subjective and objective improvement was seen in all cases. Young patients with large ventricles may benefit from shunting procedures despite low CSF pressures. These patients may be clinically identified by symptoms of new neurological dysfunction in cases of previously static neurological disease or acceleration of slowly progressive neurological dysfunction. Some of these underlying neurological disorders may predispose children and young adults to NPH.

Chiari malformation presenting in adults: a surgical experience in 127 cases.

We reviewed 127 patients who were operated upon for adult presentation Chiari malformation and made six conclusions: (a) The clinical examination remains crucial in the diagnosis. (b) The surgical anatomy is highly varied. (c) Syrinxes can be missed on preoperative contrast studies. (d) By a conservative grading system, we determined that 46% of the patients improved during long term follow-up. One-quarter deteriorated over the long run in spite of any treatment. (e) The overall results did not differ whether the treatment was plugging of the central canal plus decompression or decompression alone. (f) In patients with progression, plugging of the central canal obtained superior results. A review of the literature shows that the natural history of this complex disease process has not been established. This history is needed to identify the course of what may be several important factors that lead to the pathological condition in this disease.

Intracranial meningiomas in the aged: surgical outcome in the era of computed tomography.

Seventy-five patients older than 60 years of age underwent surgical resection of intracranial meningiomas during a 10-year period at a single institution. All patients had a computed tomographic scan preoperatively, and all were followed for at least 3 months postoperatively. There were 50 patients 61 to 70 years of age (Group A), and 25 patients older than 70 years (Group B). Sixteen patients (21%) were asymptomatic, and no patient was severely disabled preoperatively. Operative morbidity and mortality and outcome at 3 months were assessed and correlated with age, preoperative neurological status, and tumor size and location. Operative mortality was 6.6% (6% in Group A; 8% in Group B). Perioperative morbidity (including medical and surgical complications and worsening in neurological status) was 48% (46% in Group A; 52% in Group B). Neurological status 3 months after surgery was improved by at least one grade as compared to before surgery in 40% of patients (38% in Group A; 44% in Group B), unchanged in 29% (34% in Group A; 20% in Group B), and worsened in 31% (28% in Group A; 36% in Group B). While nearly half of the patients were asymptomatic 3 months after surgery, 11 patients (15%) had died or remained seriously disabled. Outcome at 3 months correlated significantly with low neurological grade preoperatively and with a tumor location over the cortical convexity. There was no significant correlation with age or tumor size. We conclude that resection of intracranial meningiomas is associated with significant morbidity and mortality in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of radiation therapy in the treatment of cerebral oligodendroglioma: an analysis of 57 cases and a literature review.

Fifty-seven cases of histologically confirmed cerebral oligodendroglioma treated at the Cleveland Clinic between 1950 and 1980 were reviewed. No difference in the 5-year survival rate was seen in patients treated with postoperative radiation therapy vs. operation alone. These data are compared to previously published series with special emphasis on the role of radiation therapy.

Needle biopsy of intrancranial lesions guided by computerized tomography.

Biopsies can be performed directly with computerized tomography (CT) head scanners with some difficulty. The small scanning orifice does not allow enough room for needle placement; therefore, biopsy is difficult. In contrast, the scanning orifice of the CT body scanner is large enough to permit biopsies without hindrance. Over 300 CT-guided abdominal biopsy procedures have been performed at the Cleveland Clinic Foundation. We are reporting the technique and the results of 14 CT-guided brain biopsies. There were no complications in the series and an accurate diagnosis was made for 13 of the 14 patients.

Simple technique for monitoring intraoperative spinal cord function.

Interference with normal spinal cord functioning is an important, although uncommon, complication of spinal surgery. Spinal evoked potentials have been advocated as a means of monitoring spinal cord transmission during operative procedures. We have developed a simple technique using electrodes inserted into the interspinal ligaments for monitoring purposes. This has produced stable and reproducible recordings with obvious clinical benefit in the first 50 cases in which it has been used.

Symptomatic Chiari malformation in adults: a new classification based on magnetic resonance imaging with clinical and prognostic significance.

Thirty-five consecutive adults with Chiari malformation and progressive symptoms underwent surgical treatment at a single institution over a 3-year period. All patients underwent magnetic resonance imaging scan before and after surgery. Images of the craniovertebral junction confirmed tonsillar herniation in all cases and allowed the definition of two anatomically distinct categories of the Chiari malformation in this age group. Twenty of the 35 patients had concomitant syringomyelia and were classified as Type A. The remaining 15 patients had evidence of frank herniation of the brain stem below the foramen magnum without evidence of syringomyelia and were labeled Type B. Type A patients had a predominant central cord symptomatology; Type B patients exhibited signs and symptoms of brain stem or cerebellar compression. The principal surgical procedure consisted of decompression of the foramen magnum, opening of the fourth ventricular outlet, and plugging of the obex. Significant improvement in preoperative symptoms and signs was observed in 9 of the 20 patients (45%) with syringomyelia (Type A), as compared to 13 of the 15 patients (87%) without syringomyelia (Type B). Postoperative reduction in syrinx volume was observed in 11 of the 20 patients with syringomyelia, including all 9 patients with excellent results. Magnetic resonance imaging has allowed a classification of the adult Chiari malformation in adults based on objective anatomic criteria, with clinical and prognostic relevance. The presence of syringomyelia implies a less favorable response to surgical intervention.