OPG-Fc treatment in growing pigs leads to rapid reductions in bone resorption markers, serum calcium, and bone formation markers.

Inhibition of the receptor activator of NF-κB ligand (RANKL) is a novel therapeutic option in the treatment of osteoporosis and related diseases. The aim of this study was to evaluate bone metabolism and structure in pigs after RANKL inhibition. 12 growing pigs were assigned to 2 groups with 6 animals each. The OPG group received recombinant human OPG-Fc (5 mg/kg IV) at day 0, the control group was given 0.9% NaCl solution. Serum levels of OPG-Fc, calcium (Ca), phosphorus (P), and bone turnover markers were evaluated every 5 days, and pigs were euthanized on day 20. Serum OPG-Fc concentration peaked at day 5 and coincided with significantly decreased Ca, P, and bone turnover markers. By day 15, measureable OPG-Fc serum levels could only be detected in 2/6 animals. With OPG-Fc clearance starting at day 10, serum Ca and P concentrations were not different between the 2 groups. TRACP5b, P1CP, and BAP levels significantly decreased by 40-70% relative to vehicle controls in the OPG-Fc group between days 5 and 10, indicating that pharmacologic concentration of OPG-Fc led to systemic concomitant inhibition of bone formation and resorption in young growing pigs. Dual X-ray absorptiometry data derived from the proximal femur did not differ between the 2 groups. µCT analysis of selected bone sites demonstrated an OPG-Fc-induced improvement of specific bone architectural indices and bone mineralization.

Future aspects of the presurgical evaluation in epilepsy.

Epilepsy surgery is a successful therapeutic approach in patients with medically intractable epilepsy. The presurgical evaluation aims to detect the epileptogenic brain area by use of different diagnostic techniques. In this review article the current diagnostic procedures applied for this purpose are described. The diagnostic armamentarium can be divided conceptually into three different groups: assessment of function/dysfunction, structural/morphologic imaging methods and functional neuroimaging techniques. Properties, diagnostic power and limits of all diagnostic tools used in the diagnostic evaluation are discussed. In addition, future perspectives and the diagnostic value of new technologies are mentioned. Some are increasingly gaining acceptance in the routine preoperative diagnostic procedure like MR volumetry or MR spectroscopy of the hippocampus in patients with temporal lobe epilepsy. Some, on the other hand, like MEG and 11C-flumazenil PET, still remain experimental diagnostic tools as they are technically demanding and cost intensive. Besides the refinement of established techniques, co-registration of different modalities like spike-triggered functional MRI will play an important role in the non-invasive detection of the epileptic seizure focus and may change the regimen of the preoperative diagnostic work up of epilepsy patients in the future.

Gamma-Knife radiosurgery of mesiotemporal tumour epilepsy observations and long-term results.

PURPOSE: The efficacy of radiosurgery in cases of mesiotemporal tumours associated with long standing epilepsy has not clearly been documented up to now. The authors present a retrospective analysis of 19 cases treated by Gamma-Knife radiosurgery (GKRS) for mesiotemporal tumour epilepsy. METHODS: Between 1992 and 1997 19 patients (12 male and 7 female) with a mean age of 31 years (5-72) and mesiotemporal tumour-induced epilepsy of a mean duration of 8.6 years (0.9-28) were treated by GKRS. All tumours were within the mesiotemporal structures and the pathohistology proven by biopsy or resective procedure revealed 15 (79%) low grade astrocytomas, 3 (16%) gangliogliomas and 1 (5%) cavernoma. Beside tumour control, the main aim of GKRS was alleviation of epilepsy by irradiating the presumed epileptic foci outside the tumour volume. The 50% isodose volumes surrounding the tumours measured a mean of 6.2 ccm (1.1-18 ccm). Doses given at marginal isodoses ranged from 12 to 30 Gy (mean 17.3 Gy). The outcome with respect to epileptic seizures was evaluated by the Engel classification. RESULTS: After a follow-up (FU) of 1.7 to 9.7 years (mean 6.5 years) 11 patients (57.9%) were significantly ameliorated (Engel I and Engel II), 7 patients (36.8%) worthwhile improved (Engel III) and 1 patient (5.3%) unchanged. In 11 patients (58%) radiosurgically induced image changes were seen on MRI. INTERPRETATION: Although microsurgical approach guided by electrocorticography (EcoG) is the state of art for treatment of mesiotemporal tumour epilepsy, GKRS can be used as a non-invasive, safe and effective alternative to resective surgery for selected cases.

Preservation of cranial nerve function following Gamma Knife radiosurgery for benign skull base meningiomas: experience in 121 patients with follow-up of 5 to 9.8 years.

INTRODUCTION: Microsurgical excision with preservation of juxtaposed neurovascular structures is considered the treatment of choice for skull base meningiomas, but there exists a great controversy regarding surgical resectability, potential risk for subsequent postoperative Cranial Nerve Deficit (CND) and the role of adjuvant or adjunctive treatment options. In this study we evaluated the effect of Gamma Knife Radiosurgery (GKRS) in 121 patients with benign basal meningiomas after a follow-up of 5 to 9.8 years. METHODS: Sixty patients had undergone open resections prior to radiosurgical treatment and 61 patients were treated by GKRS alone. Tumour volumes of 0.5 to 89.9 ccm (median 6.8 ccm) received a median marginal dose of 13 Gy (range 7-25 Gy) at the covering 25% to 80% isodose volume curves (median 45%). RESULTS: Neuroradiological controls demonstrated decreased tumour size in 73 patients (60.3%), stable meningioma volume in 47 cases (38.9%) and tumour enlargement in one patient (0.8%). Clinically, 54 patients (44.6%) improved and 61 cases (50.4%) remained unchanged. Four patients (3.3%) showed temporary and two patients (1.7%) permanent neurological deterioration (unrelated to tumour or treatment in one patient). Two patients (1.7%) developed radiation induced new or aggravated pre-existent CND (1 transient, 1 permanent) and two patients (1.7%) required further surgical resection. CONCLUSION: In our long-term experience, GKRS proved to be an attractive additional and save alternative primary treatment option in selected patients with basal meningiomas. The tumour control rate of 98.3% associated with excellent clinical outcome and low incidence for treatment related CND (1.7%) compares favourably with the reported microsurgical series.

Cranial nerve preservation after radiosurgery of vestibular schwannomas.

Radiosurgery is a management approach used to treat patients with vestibular schwannomas. The goals are long-term tumour growth control, maintenance of cranial nerve function and prevention of new deficiencies. We sought to determine long-term outcomes measuring the potential benefits against the neurological risks of primary radiosurgery. Gamma Knife radiosurgery was applied as a treatment modality for 289 patients with vestibular schwannomas from April 1992 to April 2002. The long-term results of 100 patients who underwent radiosurgery were evaluated. 60 patients received a primary treatment, 40 other cases presented with previously performed subtotal microsurgical resection or recurrence of disease (12-96 months, median 39). The median treatment volume was 3.4 ccm and the median dose to the tumour margin was 13 Gy. The median patient follow-up time was 76 months (range 60-120 months). Four tumours progressed after primary radiosurgery. Tumour control rate was 96%. Useful hearing (Gardner-Robertson I/II) was preserved in 16 patients (55%). Clinical neurological improvement occurred in 50%. Adverse effects comprised neurological symptoms (incomplete facial palsy) (House-Brackman II/III) in six cases (four recovered completely), mild transient trigeminal neuropathy in five cases, and morphological changes displaying rapid enlargement of preexisting macrocysts in two patients and tumour growth in two other patients. Microsurgical resection was performed in four cases (4%) and two patients underwent a shunting procedure because of hydrocephalus formation (2%). In patients who had undergone previous microsurgery, no new cranial nerve deficit was observed. Radiosurgery is an effective method for growth control of vestibular schwannomas and is associated with both a low mortality rate and a good quality of life. Accordingly, for the preservation of cranial nerve function radiosurgery is a useful method for the management of properly selected patients and is comparable to microsurgery.

Gamma Knife radiosurgery of brainstem gliomas.

From August 1992 until December 1999 Gamma Knife radiosurgery (GKRS) was applied to 21 patients (male to female ratio 14:7) with brainstem gliomas. Patient's median age was 23 years (8-56 years). All tumours were histologically confirmed by biopsy or open surgery: 12 low-grade gliomas and 9 malignant growths. Two lesions were located primarily in the medulla, 12 in the pons and 7 in the midbrain. A median dose of 12 Gy (9-20 Gy) was applied to the tumour margin by the median isodose of 45%. Prior to radiosurgery 4 patients were treated by conventional radiotherapy, 1 had radiotherapy and chemotherapy, 1 patient underwent chemotherapy, and 1 patient was shunted due to hydrocephalus. Neuroimaging controls (MR, CT) were obtained from 19 patients. The median interval between radiosurgery and the last neuroimaging control was 11.8 months (1-74 months). Neuroimaging depicted tumour progression in 2 patients, stable disease in 10 patients and regression in 3 cases. Follow-up periods ranged between 3 and 99 months (median 29 months). The neurological state improved in 5 patients. Microsurgical cyst fenestration was performed in 1 patient after GKRS, shunting procedure was necessary for 2 patients. Nine patients died unrelated to radiosurgery within 3 to 45 months (median 20.7 months). GKRS is an effective treatment modality for brainstem gliomas with satisfying tumour control and functional outcome.

The role of Gamma Knife radiosurgery in the management of glomus jugular tumours.

BACKGROUND: Glomus jugular tumours are usually managed by microsurgical resection and/or radiotherapy with considerable risk for treatment-related morbidity. The role of Gamma Knife Radiosurgery (GKRS) in the management of these lesions remains to be defined. METHOD: Between May 1992 and November 2000, 19 patients with glomus tumours underwent GKRS at our department. Nine patients received radiosurgery for residual or recurrent paragangliomas following microsurgical resection and in 10 cases GKRS was performed as primary treatment. The median tumour volume was 5.22 ccm (range: 0.38-33.5 ccm). Marginal doses of 12-20 Gy (median 14 Gy) were applied to enveloping isodose volume curves (Range: 30-55%, median 50%). FINDINGS: Except for an 81-year-old patient who died 9 months after radiosurgery the observation time ranged from 1.5 to 10 years (median 7.2 yrs). The total tumour control rate was 94.7% (7 cases with decreased and 11 with stable tumour size). The only patient with tumour progression (5.3%) underwent repeated radiosurgical treatment 85 months after initial GKRS. A newly diagnosed second lesion in the cavernous sinus was treated radiosurgically as well 53 months after the first Gamma Knife procedure. On clinical examination 10 patients (52.6%) presented with improved and 8 patients (42.1%) with unchanged neurological status. Deterioration in one patient (5.3%) was not related to tumour or radiosurgery. INTERPRETATION: As GKRS demonstrated to be a minimally invasive treatment alternative to microsurgery and radiotherapy with no acute or chronic toxicity it should be considered more frequently in the primary or adjuvant strategy for glomus jugular tumours.

Long term results of radiosurgery for vestibular schwannomas.

UNLABELLED: Radiosurgery is either a primary or an adjunct management approach used to treat patients with vestibular schwannomas. The goals are long-term tumour growth control, maintenance of cranial nerve function and prevention of new neurologic deficiencies. We sought to determine long-term outcomes measuring the potential benefits against the neurological risks of radiosurgery. METHODS: 278 patients with vestibular schwannomas underwent Gamma Knife radiosurgery as a treatment modality for from April 1992 to November 2001. The long-term results of 60 patients were evaluated who received radiosurgery as primary treatment. 12 cases presented with previously performed subtotal microsurgical resection or recurrence of disease (12-96 months, median 39). The median treatment volume was 3.8 ccm and the median dose to the tumour margin was 12 Gy. The median patient follow-up time was 88 months (range 72-114 months). RESULTS: Four tumours progressed after primary radiosurgery. Tumour control rate was 93%. Useful hearing (Gardner-Robertson I/II) was preserved in 16 patients (55%). Clinical neurological improvement occurred in 36 patients (60%). Adverse effects comprised neurological symptoms (incomplete facial palsy) (House-Brackman II/III) in five cases (three recovered completely), mild trigeminal neuropathy in three cases, and morphological changes displaying rapid enlargement of preexisting macrocysts in two patients and tumour growth in two other ones. Microsurgical resection was performed in three cases (5%) and one patient underwent a shunting procedure because of hydrocephalus formation. In patients who had undergone previous microsurgery, neither new cranial nerve deficit nor any tumour growth was observed. CONCLUSIONS: Radiosurgery performed with current techniques proved to be an effective method for growth control of vestibular schwannomas with both a low mortality rate and a good quality of life. An increasing percentage of patients will undergo radiosurgery as accessibility to this alternative increases, and more data regarding long-term follow-up are available. It is a post-operative complementary treatment for partially removed tumours. Accordingly, radiosurgery is a useful method for the management of properly selected patients.

Radiosurgery of residual and recurrent vestibular schwannomas.

Radiosurgery is either a primary or an adjunctive management approach used to treat patients with vestibular schwannomas. We sought to determine outcomes measuring the potential benefits against the neurological risks in patients who underwent radiosurgery after previous microsurgical subtotal resection or recurrence of the tumour after total resection. Gamma Knife radiosurgery was applied as an adjunctive treatment modality for 86 patients with vestibular schwannomas from April 1992 to August 2001. We evaluated the results of 50 patients who had a follow-up of at least 3.5 years (median 75 months, range 42-114 months). In 16 patients a recurrence of disease was observed after previous total resection. The median treatment volume was 3.4 ccm with a median dose to the tumour margin of 13 Gy. Tumour control rate was 96%. Two tumours progressed after adjunctive radiosurgery. Useful hearing (Gardner-Robertson II) (4 patients (8%)) and residual hearing (Gardner-Roberson III) (10 patients (20%)) remained unchanged in all patients, who presented with it before radiosurgery, respectively. Clinical neurological improvement was observed in 24 patients (46%). Adverse effects comprised transient neurological symptoms and signs (incomplete facial palsy, House-Brackman II/III) in five cases (recovered completely), mild trigeminal neuropathy in four cases, and morphological changes displaying rapid enlargement of a pre-existing macrocyst in one patient and tumour growth in another one. No permanent new cranial nerve deficit was observed. Radiosurgery appears to be an effective adjunctive method for growth control of vestibular schwannomas and is associated with both a low mortality rate and a good quality of life. Accordingly, radiosurgery is a rewarding therapeutic approach for the preservation of cranial nerve function in the management of patients with vestibular schwannoma in whom prior microsurgical resection failed.

Combination of surgery and gamma knife radiosurgery--a therapeutic option for patients with tumors of nasal cavity or paranasal sinuses infiltrating the skull base.

UNLABELLED: The purpose of this study was to investigate whether patients operated for skull base-infiltrating malignant tumors of the nasal cavity and/or the paranasal sinuses benefit from an additional Gamma knife radiosurgery. CASE SERIES: eight consecutive patients, (male: female ratio = 1:1, mean age = 52 years, range 34 to 79 years) presented with 2 cyclindric cell carcinomas, 2 adenocarcinomas, 2 malignant neuroblastomas, 1 squamous cell carcinoma, 1 amelanotic melanoma. Tumor stages (UICC) were: 1 T1, 3 T2, 3 T3, 1 T4, all N0, all M0. All patients were primarily treated surgically and 4 weeks later received additional stereotactic radiosurgery. Follow-up was based on computerized tomography (CT), magnetic resonance imaging (MRI), endoscopy, and biopsy. The course of disease was compared to tumor courses with surgery but without radiosurgery reported in literature. Four times endoscopic endonasal surgery (EES), once EES in combination with fluorescein technique, once EES plus external approach of frontal sinus, once lateral rhinotomy was performed. All 8 cases underwent radiosurgery (Leksell gamma knife) 4 weeks after surgery. Thirty six months after radiosurgery 6 patients were alive (4 patients without evidence of disease, 1 patient with pulmonary metastasis but without local recurrence, 1 patient with regional metastasis but no local recurrence), 1 patient died 11 months after treatment due to disease, 1 patient died due to a second malignancy. No negative or adverse effects due to radiosurgery were observed. The combination of microsurgery with Leksell Gamma knife radiosurgery appears to be an encouraging therapeutic option. To date no adverse effects have been observed in the presented cases.

[Therapy of neurotrophic keratopathy in trigeminal schwannoma with radiosurgery]. / Therapie einer neurotrophen Keratopathie bei Trigeminusschwannom mittels Radiochirurgie.

BACKGROUND: We present a patient with neurotrophic keratopathy due to a trigeminal nerve neurinoma, who was successfully treated by radiosurgery. PATIENT: A patient was referred to us with recurrent corneal erosions of unknown origin in his left eye. In addition, he suffered from mild hypoesthesia in the distribution of the first branch of the trigeminal nerve. He was started on topical lubricants (hyaluronic acid 0.5%) and antibiotic ointments (gentamycin), but since no corneal healing occurred, a soft contact lens was applied. The patient developed severe corneal neovascularization within four weeks and the contact lens had to be removed. Three months later an MRI scan was performed, which showed an intracranial tumor originating from the first branch of the trigeminal nerve. Neurinoma of the trigeminal nerve was suspected, and this presumed diagnosis was confirmed by fine needle biopsy. The patient underwent radiosurgery seven weeks later. The epithelium closed, the cornea recovered and stayed stable until the last examination 18 months after radiosurgery. CONCLUSION: Radiosurgery is a promising alternative to conventional microsurgery in cases of neurinomas of the trigeminal nerve including neurotrophic keratopathy, to keep or restore vision.

Olfactory neuroblastoma (esthesioneuroblastoma): report of six cases treated by a novel combination of endoscopic surgery and radiosurgery.

Microsurgical techniques have considerably improved the results of surgical treatment for esthesioneuroblastoma (olfactory neuroblastoma). Nevertheless, these rare tumours of the frontal skull base are still associated with high rates of tumour recurrence and mortality, thus remaining a challenge even for experienced surgeons. A novel therapeutic approach that combines endoscopic sinus surgery and radiosurgery (gamma knife) is presented here. Six patients (3 males, 3 females) aged between 27 and 75 years (median 38 years) were treated between August 1993 and July 1999. Following paranasal and nasal endoscopic sinus surgery, marginal irradiation doses ranging from 16 to 34 Gy were applied radiosurgically involving up to 7 isocentres. At present, the median follow-up period is 57 months (range: 9 - 79 months). Without mortality, tumour control was achieved in all patients. One patient, who had to undergo additional craniotomy because of extensive neoplastic infiltration, developed postoperative liquorrhea. In another case the clinical course was complicated by a bilateral frontal sinusitis. All patients complained of nasal discharge and crusts. However, a preoperative Karnovsky Index ranging from 80 to 100 % remained stable in four patients whereas an improvement was observed in two patients. Based on the favourable results observed so far, the combination of endoscopic sinus surgery and radiosurgery can be considered as promising new option for the treatment of esthesioneuroblastoma that merits further investigation.

Radiosurgery as alternative treatment for skull base meningiomas.

The effect of radiosurgical treatment of skull base meningiomas in 197 patients with a follow-up of at least 2 years was evaluated. Ninety-two of these patients had combined surgical and radiosurgical treatment, while Gamma Knife Radiosurgery (GKRS) was performed as primary treatment in 105 patients. Follow-up was available in 164 patients with intervals of 25-97 months (median 55 months) after GKRS. The imaging controls revealed decreased tumour size in 84 patients (51%), stable tumour volume in 76 ca ses (47%) and increased tumour size in 4 cases (2%). Neurological examinations showed improved neurological status in 58 cases (35%), stable clinical status in 100 patients (61%) and slight worsening in 6 cases (4%). Due to excellent tumour control rate, good clinical outcome and a low complication rate GKRS represents not only an attractive additional treatment option for basal meningiomas, but may even replace microsurgery in selected cases.

The role of gamma knife radiosurgery in children.

OBJECTS: Despite advances in microneurosurgery, the surgical management of deep-seated lesions is still associated with a high risk. Gamma knife radiosurgery (GKRS), however, has improved the outcome of cerebral tumors and arteriovenous malformations (AVMs) in delicate areas. METHODS: Between March 1992 and June 1998, 50 children (age 1-16 years) with intracranial lesions were treated with GKRS. There were 12 low-grade gliomas, 12 high-grade gliomas, 7 craniopharyngiomas, 3 hamartomas, 2 meningiomas of the skull base, 2 vestibular schwannomas, 1 pituitary adenoma, 1 choroid plexus papilloma, and 10 AVMs. The mean size of the pathologies was 4.6 cm3 (range: 0.21-25.5 cm3). A mean marginal dose of 16 Gy (8-25 Gy) was applied to a mean isodose surface of 50% (35-90%). Clinical and neuroradiological follow-up were analyzed for outcome. Follow-up periods of 45 of these patients ranged from 8 to 79 months (mean 36 months); 5 patients were lost to follow-up. Neoplasms decreased in size in 15 cases (41%), remained unchanged in 13 patients (35%), and increased in 9 cases (24%). AVMs obliterated in 3 children (38%) within 24 months. Neurological follow-up demonstrated improved clinical status in 7 patients (15.5%), stable neurological status in 31 cases (69%) and clinical deterioration in 7 patients (15.5%). The treatment was well tolerated and no complications occurred. CONCLUSIONS: GKRS represents a safe and effective treatment option for benign neoplasms or AVMs in pediatric patients and may extend survival times of children with malignant lesions.

Gamma knife surgery for epilepsy related to hypothalamic hamartomas.

OBJECTIVE: Drug-resistant epilepsy associated with hypothalamic hamartomas (HHs) can be cured by microsurgical resection of the lesions. Morbidity and mortality rates for microsurgery in this area are significant. Gamma knife surgery (GKS) is less invasive and seems to be well adapted for this indication. METHODS: To evaluate the safety and efficacy of GKS to treat this uncommon pathological condition, we organized a multicenter retrospective study. Ten patients were treated in seven different centers. The follow-up periods were more than 12 months for eight patients, with a median follow-up period of 28 months (mean, 35 mo; range, 12-71 mo). All patients had severe drug-resistant epilepsy, including frequent gelastic and generalized tonic or tonicoclonic attacks. The median age was 13.5 years (range, 1-32 yr; mean, 14 yr) at the time of GKS. Three patients experienced precocious puberty. All patients had sessile HHs. The median marginal dose was 15.25 Gy (range, 12-20 Gy). Two patients were treated two times (at 19 and 49 mo) because of insufficient efficacy. RESULTS: All patients exhibited improvement. Four patients were seizure-free, one experienced rare nocturnal seizures, one experienced some rare partial seizures but no more generalized attacks, and two exhibited only improvement, with reductions in the frequency of seizures but persistence of some rare generalized seizures. Two patients, now seizure-free, were considered to exhibit insufficient improvement after the first GKS procedure and were treated a second time. A clear correlation between efficacy and dose was observed in this series. The marginal dose was more than 17 Gy for all patients in the successful group and less than 13 Gy for all patients in the "improved" group. No side effects were reported, except for poikilothermia in one patient. Behavior was clearly improved for two patients (with only slight improvements in their epilepsy). Complete coverage of the HHs did not seem to be mandatory, because the dosimetry spared a significant part of the lesions for two patients in the successful group. CONCLUSION: We report the first series demonstrating that GKS can be a safe and effective treatment for epilepsy related to HHs. We advocate marginal doses greater than or equal to 17 Gy and partial dose-planning when necessary, for avoidance of critical surrounding structures.

Radiosurgery for epilepsy associated with cavernous malformation: retrospective study in 49 patients.

OBJECTIVE: Microsurgical resection of a cavernous malformation (CM) with or without associated cortical resection can provide efficient treatment of drug-resistant associated epilepsy. To explore the potential alternative role of radiosurgery and to evaluate its safety and efficacy for this indication, we conducted a retrospective multicenter study. METHODS: We retrospectively reviewed the files of patients with long-lasting drug-resistant epilepsy, presumably caused by CM, who were treated by gamma knife (GK) surgery for the control of their epilepsy in five centers (Marseilles, Komaki City, Prague, Graz, and Sheffield). A satisfactory follow-up was available for 49 patients (mean follow-up period, 23.66 +/- 13 mo). The mean duration of epilepsy before the GK procedure was 7.5 (+/-9.3) years. The mean frequency of seizures was 6.9/month (+/-14). The mean marginal radiation dose was 19.17 Gy +/- 4.4 (range, 11.25-36). Among the 49 patients, 17 (35%) had a CM located in or involving a highly functional area. RESULTS: At the last follow-up examination, 26 patients (53%) were seizure-free (Engel's Class I), including 24 in Class IA (49%) and 2 patients with occasional auras (Class IB, 4%). A highly significant decrease in the number of seizures was achieved in 10 patients (Class IIB, 20%). The remaining 13 patients (26%) showed little or no improvement. The mediotemporal site was associated with a higher risk of failure. One patient bled during the observation period, and another experienced radiation-induced edema with transient aphasia. Postradiosurgery excision was performed in five patients, and a second radiosurgical treatment was carried out in one patient. CONCLUSION: This series is the first to specifically evaluate the capability of GK surgery to safely and efficiently treat epilepsy associated with CM. Seizure control can be reached when a good electroclinical correlation exists between CM location and epileptogenic zone. Although we do not recommend GK surgery for prevention of bleeding for a CM that has not bled previously, our findings suggest that GK surgery can be proposed for the treatment of epilepsy when the CM is located in a highly functional area.

Junctional adhesion molecule interacts with the PDZ domain-containing proteins AF-6 and ZO-1.

We have identified the PDZ domain protein AF-6 as an intracellular binding partner of the junctional adhesion molecule (JAM), an integral membrane protein located at cell contacts. Binding of AF-6 to JAM required the presence of the intact C terminus of JAM, which represents a classical type II PDZ domain-binding motif. Although JAM did not interact with the single PDZ domains of ZO-1 or of CASK, we found that a ZO-1 fragment containing PDZ domains 2 and 3 bound to JAM in vitro in a PDZ domain-dependent manner. AF-6 as well as ZO-1 could be coprecipitated with JAM from endothelial cell extracts, demonstrating the association of the endogenously expressed molecules in vivo. Targeting of JAM to sites of cell contacts could be affected by the loss of the PDZ domain-binding C terminus. Full-length mouse JAM co-distributed with endogenous AF-6 in human Caco-2 cells at sites of cell contact independent of whether adjacent cells expressed mouse JAM as an extracellular binding partner. In contrast, truncated JAM lacking the PDZ domain-binding C terminus did not co-distribute with endogenous AF-6, but was restricted to cell contacts between cells expressing mouse JAM. Our results suggest that JAM can be recruited to intercellular junctions by its interaction with the PDZ domain-containing proteins AF-6 and possibly ZO-1.

Gamma knife radiosurgery for hypothalamic hamartomas in patients with medically intractable epilepsy and precocious puberty. Report of two cases.

Hamartoma of the hypothalamus represents a well-known but rare cause of central precocious puberty and gelastic epilepsy. Due to the delicate site in which the tumor is located, surgery is often unsuccessful and associated with considerable risks. In the two cases presented, gamma knife radiosurgery was applied as a safe and noninvasive alternative to obtain seizure control. Two patients, a 13-year-old boy and a 6-year-old girl, presented with medically intractable gelastic epilepsy and increasing episodes of secondary generalized seizures. Abnormal behavior and precocious puberty were also evident. Magnetic resonance (MR) imaging revealed hypothalamic hamartomas measuring 13 and 11 mm, respectively. After general anesthesia had been induced in the patients, radiosurgical treatment was performed with margin doses of 12 Gy to 90% and 60% of isodose areas, covering volumes of 700 and 500 mm3, respectively. After follow-up periods of 54 months in the boy and 36 months in the girl, progressive decrease in both seizure frequency and intensity was noted (Engel outcome scores IIa and IIIa, respectively). Both patients are currently able to attend public school. Follow-up MR imaging has not revealed significant changes in the sizes of the lesions. Gamma knife radiosurgery can be an effective and safe treatment modality for achieving good seizure control in patients with hypothalamic hamartomas.

Staged radiosurgical treatment for large benign cerebral lesions.

OBJECT: Large brain lesions are considered unamenable to gamma knife treatment because of possible adverse effects. The proximity of eloquent brain to a target location, including some arteriovenous malformations (AVMs), still poses a challenge to the neurosurgeon. Because meningiomas and AVMs often show a slow or absent growth rate, partial radiosurgical treatment in cases with risk of unacceptable surgery-related morbidity is an alternative. The authors evaluated the results of staged treatment. METHODS: Since April 1992, 12 patients suffering from large benign tumors (meningiomas) and seven with AVMs considered inoperable underwent gamma knife radiosurgery in staged procedures. All patients with tumors underwent primary open surgery for partial removal of recurrent growth and subsequent radiosurgical treatment. Four men and eight women ranging in age from 26 to 73 years harbored tumors that ranged in volume from 19 to 90 cm3. Marginal dose ranged from 10 to 25 Gy prescribed in the 30 to 50% isodose. The time interval between the radiosurgical treatments varied from 1 to 8 months. Follow up ranged from 5 and 89 months. Three female and four male patients (age range 10-48 years) had undergone previous AVM embolization and were treated with margin doses of 18 to 22 Gy in the 40 to 50% isodose. The volume range of these AVMs was 11 to 25 cm3. The time interval between radiosurgical treatments ranged from 5 to 36 months. The mean follow up was 22.6 months. Neurological follow-up examinations showed clinical improvement in 11 patients (58%), whereas five (26%) remained unchanged. Among tumor patients no deterioration or further tumor growth was observed. Tumor necrosis demonstrated noticed in five patients (26%). One patient with an AVM suffered from seizures and hemiparesis. Follow-up magnetic resonance imaging of the residual nidus disclosed no rebleeding. CONCLUSIONS: For selected patients with large benign lesions staged gamma knife radiosurgery could be an alternative, as evidenced by the authors' series in which there was no mortality and low incidence morbidity.