Grading of vestibular schwannomas and corresponding tumor volumes: ramifications for radiosurgery.

BACKGROUND: Patients with vestibular schwannomas (VS) are either assigned to watchful waiting, microsurgical resection, or radiosurgery. Decision making on how to proceed is based on parameters such as age, tumor growth, loss of hearing, and the tumor's Koos grading. METHODS: In order to correlate Koos grading with tumor volume, patient records of 235 patients with VS who underwent Gamma Knife radiosurgery (GKRS) were retrospectively reviewed. RESULTS: From 1994 to 2009, 235 consecutive patients underwent GKRS for sporadic VS at the Zurich Gamma Knife Center. Median follow up was 62.8 ± 33.0 months. Of the 235 tumors, 32 (13.6 %) were graded Koos I with a volume of 0.25 ± 0.3 cc; 71 (30.2 %) were graded Koos II with a volume of 0.57 ± 0.54 cc; 70 (29.8 %) were graded Koos III with a volume of 1.82 ± 1.88 cc; and 62 (26.4 %) were graded Koos IV with a volume of 4.17 ± 2.75 cc. Tumor progression was defined as a volume increase > 20 % at 2 years or later following GKRS. Overall tumor progression occurred in 21/235 (8.9 %) patients at 3.4 ± 0.9 years. Tumor progression did not differ statistically significantly in the various Koos grades: 1/32 (3.1 %) patients with VS Koos Grade I, 7/71 (9.8 %) patients with VS Koos Grade II, 6/70 (8.6 %) patients with VS Koos Grade III, and 7/62 (11.3 %) patients with VS Koos Grade IV. CONCLUSION: To our knowledge, this is the first work correlating the various Koos grades of VS to their respective tumor volumes. In our patients, tumor volumes of VS Koos Grade IV were limited because all of our patients were eligible for radiosurgery. In our series, the outcome following GKRS for patients with VS Koos Grade IV tumors did not differ from patients with VS Koos Grades I-III. We therefore suggest to limit Koos Grade IV VS to tumor volumes < 6 cc that may be eligible for radiosurgery, and introduce an additional VS Grade V for large VS with tumor volumes of > 6 cc that may not be eligible for radiosurgery.

Extrasellar, intracavernous sinus adrenocorticotropin-releasing adenoma causing Cushing's disease.

This report describes a patient with pituitary-dependent Cushing's disease who had a preoperative ACTH gradient to the left at the level of the cavernous sinus. Intraoperatively, an adenoma was found entirely within the left cavernous sinus, with no direct connection to the pituitary gland. To our knowledge, such a tumor has not been reported previously. This case has implications for the diagnosis, treatment, and follow-up of patients with pituitary-dependent Cushing's disease. The presence of an entirely extrasellar ACTH-releasing adenoma in the cavernous sinus could explain why pituitary-dependent Cushing's disease may persist postoperatively, even after total hypophysectomy. The diagnosis of an intracavernous tumor can be established by cavernous sinus venography. An extrasellar intracavernous adenoma can be diagnosed intraoperatively after careful negative exploration of the sellar contents followed by incision of the cavernous sinus on the side of the ACTH gradient established by venous sampling.

Extensive splice variation and localization of the EHK-1 receptor tyrosine kinase in adult human brain and glial tumors.

EHK-1 is a neuronal ELK-related receptor tyrosine kinase which interacts with multiple, membrane-anchored ligands. Recent experiments have suggested a role for some of these ligands in the formation of neuronal pathways. Here, we report the isolation of human EHK-1 cDNAs and the localization of the human EHK-1 gene to chromosome 4q12. Six EHK-1 mRNA splice variants encoding cell-surface receptors with catalytic domains were identified in adult human brain where a 120-kDa EHK-1 protein predominates. Immunohistochemistry for EHK-1 reveals a dendritic staining pattern in cortical neurons and cerebellar Purkinje cells and a marked accumulation of EHK-1 in the somas of pyramidal neurons within the cortex and hippocampus. Interestingly, we have identified lineage aberrant expression of EHK-1 in a number of human gliomas. In addition to functions during development, EHK-1 may be involved in the maintenance of the adult nervous system and contribute to glioma development.

Pediatric pituitary adenomas.

Previous series of pediatric pituitary adenomas have been small and have not been analyzed by age group. We analyzed the frequency, manifestation, course, and biology of these tumors before, during, and after puberty in 136 children younger than 20 years old at surgery, identified by review of 2230 patients treated from 1969 to 1993. Tumors were classified by clinical phenotype. Adrenocorticotropic hormone-releasing adenomas were most common before puberty, and prolactinomas were most common during and after. The frequencies of adrenocorticotropic hormone-releasing adenomas, prolactinomas, and endocrine-inactive adenomas differed from those in adults. Growth arrest was common with all types except growth hormone (GH)-releasing adenomas; menstrual irregularities were common with all but adenomas causing Nelson syndrome. Among girls with prolactinomas, the preoperative duration of primary amenorrhea was longer than that of other symptoms. Tumor size differed by adenoma type. Serum hormone levels shortly after surgery correlated with the recurrence of prolactinomas and GH-releasing adenomas. The prolactinoma size correlated with the maximum preoperative serum prolactin level; boys had larger tumors and higher preoperative and postoperative prolactin levels. We conclude that pediatric pituitary adenomas vary in size, age at symptom onset, and frequency before, during, and after puberty. Most adenomas can cause menstrual irregularities, and primary amenorrhea should prompt investigation of the sella. Growth arrest is common with all adenomas except GH-releasing adenomas. Serum prolactin and GH levels measured at 1 to 5 days after surgery indicate the risk of recurrence of prolactinomas and GH-releasing adenomas, respectively.

Changes in the immunophenotype of recurrent pituitary adenomas.

Only two cases have been reported of a pituitary adenoma that changed phenotype between its initial resection and recurrence. To determine the frequency of such cases among our patients, we examined the clinical course of these tumors and characterized any patterns. We reviewed the charts of 1023 patients with pituitary adenomas who underwent surgery between 1984 and 1992 at the University of California at San Francisco. Of the 65 patients (6.4%) who had operations for or clinical evidence of tumor recurrence, five (7.7%) had tumors that changed phenotype. The female-to-male ratio was 4:1, and age at the onset of symptoms was 33.2 +/- 15.3 years (mean +/- standard deviation). Changes occurred in hormone production and hormone release after 6.4 +/- 3.4 years. At some point, all five tumors were invasive and four were macroadenomas. Two patients had more than one operation for tumor recurrence; three had silent or symptomatic pituitary apoplexy; and three had undergone sellar irradiation before the changes in phenotype occurred. The behavior of these tumors therefore seems to be aggressive. We do not yet know whether phenotypic changes in pituitary adenomas have any treatment implications. Therefore, we advocate the complete immunostaining of primary and recurrent pituitary adenomas so that additional data about their clinical course can be collected.

Symptomatic granular cell tumor of the pituitary gland: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: The posterior pituitary lobe is rarely the site of symptomatic primary tumors. The most common lesions arising from the neurohypophysis and the pituitary stalk seem to be granular cell tumors (GCTs), of which only 42 symptomatic cases have been reported. Here we present an unusually well-documented case of a GCT, which has implications for the differential diagnosis of sellar masses. CLINICAL PRESENTATION: A 75-year-old woman presented with decreased visual acuity, visual field loss, and a 2-year history of progressive vertigo and headaches. Neuroradiological studies showed a supra- and intrasellar, 25 x 20-mm mass, containing calcifications, that compressed the optic chiasm and extended into the third ventricle. INTERVENTION: The tumor was subtotally resected through a transsphenoidal approach. The tumor was tough and vascular and could not be suctioned. Histological examination revealed a typical GCT. The postoperative course was uneventful. Residual tumor was treated with fractionated radiation therapy. Ophthalmological testing 10 months after surgery showed a slight improvement in the visual symptoms. CONCLUSION: Tumor calcifications in computed tomographic scans do not exclude a GCT. The diagnosis requires histological confirmation. Surgical removal by the transsphenoidal approach is the therapy of choice, as for other sellar tumors. Radiation therapy may be advisable after subtotal resection. Our literature review suggests the possibility of gender-related tumor biology in GCTs.

Thyrotropin-producing pituitary adenomas.

To evaluate the biology of thyrotropin (TSH)-producing pituitary adenomas, the authors reviewed the charts of 19 patients who underwent transsphenoidal surgery within a 15-year period at the University of California, San Francisco (UCSF). Between 1989 and 1991, the period during which immunostaining techniques were used consistently for diagnosis, 2.8% of the pituitary adenomas treated at UCSF were TSH-producing. The rate of reoperation for tumor recurrence was 10.5%. Before pituitary surgery, more than one-third of the 19 patients had undergone thyroid ablation. Two patients had a history of Hashimoto's thyroiditis. The female:male ratio was 1.7:1. Women tended to develop these tumors at a younger age and had a longer history of symptoms but their tumors were smaller and less often invasive than those seen in men. About 50% of the tumors were purely TSH-producing and 50% were plurihormonal, including five that produced both TSH and adrenocorticotroph hormone. All tumors were macroadenomas. Before surgery, 46% of the patients had abnormal electrocardiographic findings; 16% had a rapid onset of severe neurological conditions either before or after surgery. It is concluded that TSH-producing adenomas are more common in patients who undergo surgical treatment than was previously thought. In addition, they occur more frequently in women, have a different biology in women than in men, and tend to be associated with potentially life-threatening cardiovascular and neurological complications.

Interhemispheric pressure gradients in severe head trauma in humans.

Interhemispheric pressure gradients may occur following severe head trauma in patients even in the absence of intracranial space occupying lesions. A higher ICP of the contralateral hemisphere may escape routine unilateral ICP monitoring. Clinical signs and CT scans do not seem to predict reliably a lateralized ICP. According to our data with a limited number of patients, interhemispheric pressure gradients seem to occur in the initial posttraumatic phase in some patients, and they seem to resolve following adequate ICP treatment after several hours. Therefore, simultaneous bilateral ICP measurement may be warranted in the initial posttraumatic phase.

Pressure gradients within the central nervous system.

The existence of clinically relevant pressure gradients within the central nervous system (CNS) is the subject of ongoing debate. Such gradients, if they do exist, would have significant implications for intracranial pressure (ICP) monitoring and ICP management in traumatic brain injury. As summarised in this short review, there is considerable experimental and clinical evidence that ICP is not evenly distributed within the central nervous system. Larger clinical trials on the implications of ICP gradients are warranted to address questions on the correct placement of ICP probes and on ICP management. It seems paradoxical to develop and employ ever more sophisticated monitoring devices in traumatic brain injury, such as monitoring of CNS metabolites with microdialysis or near-infrared spectroscopy, while fundamental issues such as the existence of ICP gradients remain unresolved.

[Palliative treatment of brain metastases with gamma knife]. / Palliative Behandlung von Hirnmetastasen mit dem Gamma Knife.

The gamma knife is a stereotactic radiosurgery device which allows well defined, deep seated brain tumors or arteriovenous malformations with a maximal volume of about 25 ccm and a diameter not greater than 3.5 cm, to be treated in a single session under local anesthesia. The gamma knife offers an alternative treatment method to the classical approach of treating brain metastases by surgical excision and/or whole brain radiotherapy. The advantages of this technique are evident: the method is non-invasive, the treatment is carried out in a single session with a very short hospitalisation of two to three days, it is exempt from physical and psychical stress, the head does not need to be shaved and no hair loss occurs, a good quality of life is obtained for a reasonably prolonged survival time and it offers an economically favourable treatment method. Up to December 1999, over 30,000 patients suffering from brain metastases have been treated worldwide using the gamma knife. In Zürich, from September 1994 to December 2000 140 received this treatment. In the literature selection criteria may differ, and this may have determined some of differences in outcome. However, our results are comparable with those in the majority of publications with an average survival time of 263 days and a maximum survival of 1080 days. Good prognostic factors for survival and local control of brain metastases are a Karnofsky Performance Scale Score approaching 90 to 100, but not lower than 70, tumour volume, controlled primary cancer, and absence or stable extracranial metastases.

[Cerebral microdialysis in neurological and neurosurgical research and clinical application in neurology and neurosurgery]. / Zerebrale Mikrodialyse in neurologischer und neurochirurgischer Forschung und klinische Anwendung in Neurologie und Neurochirurgie.

Microdialysis of the cerebral extracellular space (CES) provides information on the cortical metabolic state by measurement of the concentrations of metabolites and transmitters as well as of the extracellular pH. In trauma patients, this kind of monitoring should reveal damage from secondary cortical ischemia in an early, hopefully reversible state. The method further allows in vivo measurement of drug levels in the CES and investigation of their effect on metabolism. Although microdialysis has mainly been used experimentally, it is now beginning to be applied clinically. We report on our experience with both experimental and clinical work.

Transient MR changes and symptomatic epilepsy following gamma knife treatment of a residual GH-secreting pituitary adenoma in the cavernous sinus.

OBJECTIVE: To report a rare side effect of gamma knife treatment of pituitary macroadenoma. CASE REPORT: In a forty-one-year old female patient acromegaly was diagnosed due to a growth hormone secreting pituitary macroadenoma. Following transsphenoidal surgery the patient underwent gamma knife treatment for persistent uncontrolled acromegaly activity of residual tumor, infiltrating the left cavernous sinus. 15 months later, complex partial seizures were diagnosed and 17 months after gamma knife treatment a gadolinium enhancing lesion was detected in her left medial temporal lobe. Radiation induced changes, radiation necrosis or a glioma were considered. Neuropsychological testing indicated potentially significant post-surgical deficits. Therefore, surgical action was postponed and anti-epileptic treatment was started. Four months later she was free of seizures and an MR scan showed an almost complete regression of the gadolinium enhancing lesion, indicating that it had been due to radiation induced changes. CONCLUSION: Gamma knife surgery of a pituitary adenoma may cause radiation induced MR changes of the mesial temporal lobe mimicking glioma or radionecrosis and cause symptomatic epileptic seizures. The awareness of this rare complication is important to avoid unnecessary and potentially harmful diagnostic or therapeutic interventions.

Randomized placebo-controlled trial of single-dose antibiotic prophylaxis with fusidic acid in neurosurgery.

In neurosurgery, the antibiotic prophylaxis of choice has not yet been determined. The ideal drug should have an appropriate antimicrobial spectrum and favourable pharmacokinetic properties. In addition it should be nontoxic and easy to apply. We therefore conducted in 90 patients a prospective, randomized, placebo-controlled, double-blind trial in clean neurosurgery at increased risk of wound infection using a single pre-operative dose of 500 mg fusidic acid. Fusidic acid is a steroid-like antibiotic with a serum half-life of about 10 hours and excellent activity against gram-positive bacteria, including methicillin-resistant staphylococci. The neurosurgical infection rates for craniotomies, posterior fossa surgery and implantation of foreign bodies were 2.4% in the treatment group and 9.1% in the placebo group, respectively. This difference is statistically significant at a 95% confidence level.

Significant lateralisation of supratentorial ICP after blunt head trauma.

After blunt head trauma simultaneous left and right hemispheric intracranial pressure (ICP) monitoring revealed a pressure gradient of about 30 mmHg persisting until the 5th day after the accident equilibrating thereafter. ICP was elevated over the radiologically more compressed hemisphere. The supratentorial space seems to allow considerable interhemispheric pressure gradients. As a consequence epidural ICP monitoring should be performed over the hemisphere with signs of greater compression.

Age-related and gender-related occurrence of pituitary adenomas.

OBJECTIVE: To evaluate the various types of pituitary adenomas according to sex and age group. Few studies have attempted such an analysis, and most have focused on specific age groups, especially children. Recent data suggest that the frequency of different types of pituitary adenomas varies according to age and sex. DESIGN: A retrospective review of the records of 2230 patients who underwent surgery for a pituitary adenoma at the University of California, San Francisco (UCSF), between January 1969 and June 1993. METHODS: The distribution of tumours was analysed according to age at surgery, sex, and the clinical phenotype of the tumour. Age groups were defined as the decades of life. RESULTS: Prolactinomas were the most common tumours (39%), followed by endocrine-inactive adenomas, growth-hormone-releasing adenomas, and adrenocorticotrophic hormone-releasing adenomas causing Cushing's disease; ACTH-releasing adenomas causing Nelson's syndrome and thyrotrophin (TSH)-releasing adenomas were rare. The female-to-male ratio differed considerably between the various adenoma types and between age groups. Prolactinomas, ACTH-releasing adenomas, and TSH-releasing adenomas occurred mostly in females; endocrine-inactive and GH-releasing adenomas occurred mostly in males. In older age groups, all adenoma types, except for endocrine-inactive adenomas, tended to assume a more balanced gender distribution. Among patients with prolactinomas, endocrine-inactive, ACTH-releasing, and to a lesser extent GH-releasing adenomas, the greatest discrepancy in gender distribution seemed to coincide with the peak occurrence of each tumour type. The peak occurrence was from the second to the fifth decade of life for prolactinomas and from the fourth to the eighth decade for endocrine-inactive adenomas. GH-releasing, ACTH-releasing, and TSH-releasing adenomas were more evenly distributed throughout the adult life span. CONCLUSIONS: The frequency of pituitary adenomas varies greatly according to age and sex. The various adenoma types have their peak occurrence in distinctly different age groups and differ greatly in their female-to-male ratios. The female-to-male ratio for a given adenoma type varies greatly with age.

[In which operations is antibiotic prevention carried out with only a a single dose? Results of a survey among chief physicians in general surgery in German-speaking Switzerland]. / Bei welchen Operationen wird eine Antibiotika-Prophylaxe mit nur einer Dosis durchgeführt? Ergebnisse einer Umfrage unter allgemeinchirurgischen Chefärzten der deutschsprachigen Schweiz.

We have been asking 108 surgeons in chief of the German speaking part of Switzerland in what operations they are giving an antibiotic prophylaxis. We wanted to know how far the application of the single-dose concept has been entering every day's practice in Switzerland. Its value has been proven in several prospective, randomized, controlled studies. Out of 84 valid questionnaires we could see that single-dose prophylaxis has not yet come into common use, although it is not only more reasonable but also less expensive than a prolonged course. Fortunately, already 90% of the surgeons are giving an antibiotic prophylaxis in colorectal surgery and 53% in biliary tract surgery. A majority of surgeons do not yet provide antibiotic prophylaxis in gastric surgery nor in appendectomies, where the single-dose prophylaxis is effective as well.

Rifampin concentrations in various compartments of the human brain: a novel method for determining drug levels in the cerebral extracellular space.

Antimicrobial therapy for brain infections is notoriously difficult because of the limited extent of knowledge about drug penetration into the brain. Therefore, we determined the penetration of rifampin into various compartments of the human brain, including the cerebral extracellular space (CES). Patients undergoing craniotomy for resection of primary brain tumors were given a standard dose of 600 mg of rifampin intravenously before the operation. A microdialysis probe (10 by 0.5 mm) was inserted into the cortex distantly from the resection and was perfused with two different rifampin solutions. Rifampin concentrations in the CES were calculated by the no-net-flux method. Intraoperatively, samples were taken from brain tumor tissue, perifocal tissue, and normal brain tissue in the case of pole resections. Rifampin concentrations in the various samples were determined by using a bioassay with Sarcinea lutea. In the various compartments, rifampin concentrations were highest within tumors (1.37 +/- 1.34 microg/ml; n = 8), followed by the perifocal region (0.62 +/- 0.67 microg/ml; n = 8), the CES (0.32 +/- 0.11 microg/ml; n = 6), and normal brain tissue (0.29 +/- 0.15 microg/ml; n = 7). Rifampin concentrations in brain tumors do not adequately reflect concentrations in normal brain tissue or in the CES. Rifampin concentrations in the CES, as determined by microdialysis, are the most reproducible, and the least scattered, of the values for all compartments evaluated. Rifampin concentrations in all compartments exceed the MIC for staphylococci and streptococci. However, CES concentrations may be below the MICs for some mycobacterial strains.

Treatment of syringomyelia after posttraumatic paraparesis or tetraparesis.

This retrospective study of 12 patients with syringomyelia related to spinal cord trauma with paraplegia or tetraplegia and secondary progressive neurologic deficits was conducted to evaluate various surgical treatments. Judging by the results of postoperative neuroradiologic examinations, 75% had incomplete reduction of the spinal fracture at the time of initial surgery. The secondary neurologic deterioration occurred within a delay of 146 +/- 16 months and included ascending sensory deficits in 92%, deafferentation pain in 83%, and increased motor weakness in 33%. There was a positive correlation between the severity of symptoms, incomplete reduction of spinal fracture, and the degree of arachnoid scarring in preoperative neuroradiologic examinations. Syringoperitoneal shunting was performed in 83% of patients, and laminectomy with arachnoid lysis and dural grafting were performed in 17%. Pain was improved in 75%, sensory deficits in 25%, and motor weakness in 8%. During the follow-up period of 44 +/- 25 months, 30% of patients with syringoperitoneal shunting required repeated operation for obstruction or infection, whereas the syringomyelia remained collapsed in the two patients with laminectomy with arachnoid lysis and dural grafting, but this did not require additional surgery. In conclusion, laminectomy with arachnoid lysis and dural grafting seems to be a promising alternative treatment for patients with secondary neurologic deterioration after traumatic paraplegia or tetraplegia. Syringoperitoneal shunting may be reserved for patients without severe arachnoid scarring.

Penetration of fusidic acid into human brain tissue and cerebrospinal fluid.

Penetration of fusidic acid into brain tissue in six patients and cerebrospinal fluid in seven patients was determined. Tissue samples, taken during surgery revealed drug levels at about 7% of simultaneous serum concentrations. In contrast, cerebrospinal fluid concentrations were below 1% of serum levels. Since serum- and tissue levels of fusidic acid were far above the minimal inhibitory concentration (MICs) of staphylococci and streptococci, and since it has a long serum half-life of about 10 hours, it is a promising candidate for prophylaxis in neurosurgery.