Long-term results of fractionated stereotactic radiotherapy as third-line treatment in acromegaly.

The treatment of acromegaly is based on surgery, drugs, and radiotherapy as a third-line option. Fractionated stereotactic radiotherapy (FSRT) is a new technique with a need for long-term evaluation. The purpose of the study was to evaluate long-term results of FSRT in acromegaly. Overall, 34 patients [sex ratio 1.12, age 45 (5-65) years] with a pituitary adenoma of 24.5 (9-76) mm including 20 invasive tumors were treated by radiotherapy in fractionated stereotactic conditions delivering 50 gy in 27 sessions. Baseline growth hormone (GH) and IGF1 levels were 18 (±14.5) and 632.6 (±339) µg/L, respectively. Indications of FSRT were failure of surgery and drug treatments (n = 30) or contraindication/refusal of surgery (n = 4). Hormonal control was defined by normal age- and sex-adjusted IGF1. Remission was defined by hormonal control after withdrawal of drugs for a minimum of three consecutive months. Data were analyzed in SPSS software with a significance level at p < 0.05. After a mean follow-up of 152 months, hormonal control was achieved in 33 patients (97 %) with withdrawal of drugs in 13 patients (38.2 %) without any recurrence. Factors found to be significantly associated to remission in a multivariate Cox regression were lower baseline hormone levels (GH and IGF1) and smaller tumor size. Tumor control was achieved in all patients. Acquired hypopituitarism after radiotherapy was the main side effect reported with a rate of 39 %. FSRT seems to be an effective and well tolerated third-line treatment of acromegaly, particularly adapted to macro adenomas treatment.

Transglabellar approach for resection of anterior midline skull base meningiomas: technical note.

BACKGROUND: We describe our experience of minimally invasive approach of the anterior skull base through the transglabellar approach. METHOD: The technical details of the transglabellar approach are described in this article as we have been using it for the past 3 years. After an inter-eyebrow skin incision, the scalp is elevated allowing the creation of a 3-cm bone flap in the frontal sinus, which gives direct access to the anterior midline skull base. Removal of the tumour is carried out without brain retraction. The closure requires obstruction of nasofrontal ducts and sinus mucosa removal. RESULTS: We operated on 24 patients using this approach. The tumour was completely removed in every case. We reported one case of meningitis and three cerebrospinal fluid leaks. Every patient was satisfied with the aesthetic results. CONCLUSIONS: The transglabellar approach is a reasonably easy and efficient way to resect anterior midline skull base meningiomas.

Prognostic value of retinal nerve fiber layer thickness for postoperative peripheral visual field recovery in optic chiasm compression.

UNLABELLED: OBJECT.: The authors' objective was to evaluate the predictive value of preoperative axonal loss for peripheral visual field recovery after surgery for optic chiasm compression. METHODS: Consecutive patients with optic chiasm compression in the period from October 2010 through August 2012 were retrospectively studied. Time-domain optical coherence tomography (OCT) had been performed before surgery. Kinetic automated perimetry had been performed before and after surgical decompression. The area of the peripheral isopter (square degrees [deg(2)]) was assessed. Postoperative improvement was defined as an increase of 25 deg(2) or more. RESULTS: Sixty-eight eyes in 34 patients were included in the analysis. In 44 eyes the visual field improved after surgery, and in 24 eyes it was unchanged or worse. Nasal retinal nerve fiber layer (RNFL) thickness was a good prognostic factor for peripheral visual field recovery (OR 1.56 per 15 µm, p = 0.041). CONCLUSIONS: Peripheral visual field recovery after surgery for optic chiasm compression is predicted by nasal RNFL thickness, which is in accordance with the retinotopy of retinal ganglion cells, as nasal axons decussate at the optic chiasm.

Fractionated stereotactic radiotherapy for acoustic neuromas: a prospective monocenter study of about 158 cases.

PURPOSE: To evaluate long-term outcomes and efficacy of fractionated stereotactic radiotherapy in the treatment of acoustic neuromas. MATERIAL AND METHODS: Between January 1996 and December 2009, 158 acoustic neuromas were treated by FSR in 155 patients. They received a dose of 50.4 Gy, with a safety margin of 1-2mm with a median tumor volume at 2.45 mL (range: 0.17-12.5 mL) and a median follow-up duration at 60 months (range: 24-192). RESULTS: FSR was well tolerated in all patients with mild sequelae consisting in radiation-induced trigeminal nerve impairments (3.2%), Grade 2 facial neuropathies (2.5%), new or aggravated tinnitus (2.1%) and VP shunting (2.5%). The treatment failed in four patients (2.5%) who had subsequent surgery respectively at 20, 38, 45 and 84 months post-FSR. The local tumor control rates were respectively 99.3%, 97.5% and 95.2% at 3, 5 and >7-year of follow-up. For initial Gardner-Robertson Grade 1 and 2 ANs, the preservation of useful hearing was possible in 54% of the cases; only Grade 1 ANs had stabilized during the course of the follow-up with 71% >7 years. However, hearing preservation was not correlated to the initial Koos Stage and to the radiation dose delivered to the cochlea. Tinnitus (70%), vertigo (59%), imbalance (46%) and ear mastoid pain (43%) had greatly improved post-FRS in most patients. Tumor control, hearing preservation and FRS toxicity were quite similar in patients with NF2, cystic acoustic neuroma, prior surgical resection and Koos Stage 4 AN. No secondary tumors were observed. CONCLUSION: FSR is a safe and effective therapeutic for acoustic neuromas and could be an alternative to microsurgery. Compared to radiosurgery, there are no contraindications for fractioned doses of stereotactic radiotherapy especially for Stage-4 tumors and patients at high risk of hearing loss.

Implanted carmustine wafers followed by concomitant radiochemotherapy to treat newly diagnosed malignant gliomas: prospective, observational, multicenter study on 92 cases.

OBJECTIVES: Study the feasibility and effectiveness of a treatment associated surgery, intraoperative chemotherapy (carmustine wafers), and concomitant radiochemotherapy (temozolomide) for the management of newly diagnosed, high-grade gliomas. METHODS: Prospective multicenter study conducted in 17 French centers with a total of 92 patients with newly diagnosed malignant glioma treated by surgery, implanted Carmustine wafers (Gliadel(®)) followed by concomitant radiochemotherapy by temozolomide (Temodar(®)). Clinical, imaging, and survival data were collected to study toxicity-induced adverse events and efficacy. RESULTS: A total of 20.6 % presented with adverse events during surgery, potentially attributable to carmustine, including 5 severe infections. Afterwards, 37.2 % of patients showed adverse events during radiochemotherapy and 40 % during adjuvant chemotherapy by temozolomide. We report a 10.5-month, median, progression-free survival and an 18.8-month median overall survival. No significant statistical difference was observed according to age, Karnofsky Performance Scale, or grade of the tumor. A prognostic difference at the limit of the significance threshold was observed according to the extent of the resection. CONCLUSIONS: Multimodal treatment associating implanted carmustine chemotherapy and concomitant radiochemotherapy with temozolomide seems to yield better survival rates than those usually described when carmustine or temozolomide are used alone independently from one another. These interesting results were obtained without increased adverse events and would need to be validated during a phase 3 study.

[Treatment for intracranial aneurysms]. / Traitement des anévrismes intracrâniens.

Aneurysm rupture is suspected in case of sudden, intense headache, sometimes associated with nausea or vomiting, focal neurologic deficit or loss of consciousness. Aneurysm rupture is a diagnostic and therapeutic emergency that has to be managed in highly specialized centers. Ruptured aneurysms have to be treated in emergency to avoid rebleeding. Endovascular approach is the first line treatment. The indications for treatment of unruptured have to be discussed according to several factors including patient's age, aneurysm size and location. Follow-up examinations are needed after aneurysm treatment (CTA, MRA, DSA). According to aneurysm risk factors, patients with aneurysms have to stop smoking and their blood pressure should be controlled on a regular basis and treated if needed.

Randomized, double-blind, placebo-controlled, pilot trial of high-dose methylprednisolone in aneurysmal subarachnoid hemorrhage.

OBJECT: The object of this study was to determine the efficacy of methylprednisolone in reducing symptomatic vasospasm and poor outcomes after subarachnoid hemorrhage (SAH). METHODS: Ninety-five patients with proven SAH were recruited into a double-blind, placebo-controlled, randomized trial. Starting within 6 hours after angiographic diagnosis of aneurysm rupture, placebo or methylprednisolone, 16 mg/kg, was administered intravenously every day for 3 days to 46 and 49 patients, respectively. Deterioration, defined as development of a focal sign or decrease of more than 1 point on the Glasgow Coma Scale for more than 6 hours, was investigated by using clinical criteria and transcranial Doppler ultrasonography, cerebral angiography, or CT when appropriate. The end points were incidence of symptomatic vasospasm (delayed ischemic neurological deficits associated with angiographic arterial narrowing or accelerated flow on Doppler ultrasonography, or both) and outcome 1 year after entry into the study according to a simplified Rankin scale (Functional Outcome Scale [FOS]) in living patients and the Glasgow Outcome Scale in all patients included. RESULTS: All episodes of deterioration and all living patients with a 1-year outcome were assessed by a review committee. In patients treated with methylprednisolone, the incidence of symptomatic vasospasm was 26.5% compared with 26.0% in those given placebo. Poor outcomes according to FOS were significantly reduced in the Methylprednisolone Group at 1 year of follow-up; the risk difference was 19.3% (95% CI 0.5-37.9%). The outcome was poor in 15% (6/40) of patients in the Methylprednisolone Group versus 34% (13/38) in the Placebo Group. CONCLUSIONS: A safe and simple treatment with methylprednisolone did not reduce the incidence of symptomatic vasospasm but improved ability and functional outcome at 1 year after SAH.

Incidence of basioccipital hypoplasia in Chiari malformation type I: comparative morphometric study of the posterior cranial fossa. Clinical article.

OBJECT: The chronic tonsillar herniation defining Chiari malformation Type I (CMI) is thought to result from overcrowding of a normally developing hindbrain within a congenitally small posterior cranial fossa (PCF) due to occipital hypoplasia. The goals in the present study were to authenticate the cranioencephalic disproportion in a group of patients with CMI and to discuss new developmental aspects according to which part of the occipital bone was underdeveloped. METHODS: The authors retrospectively examined a group of 17 patients with CMI. Measurements of osteotentorial and neural structures of the PCF were made on MR images of the brain. The results were compared with findings in 30 healthy controls by using the Mann-Whitney U-test. RESULTS: Dimensions of the neural structures did not differ between the 2 groups of patients. The mean length of the basiocciput was significantly shorter in the CMI group (19.4 mm) compared with the control group (25.7 mm; p = 0.0003). The mean diameter of the foramen magnum was larger in the CMI group, but this difference was not statistically significant. The dimensions of the supraocciput and the mean angle of the cerebellar tentorium were identical in the 2 groups. CONCLUSIONS: Data in this study support the idea that occipital hypoplasia is the main cause of overcrowding within the PCF. Basioccipital shortness is a cardinal feature of the resultant shallow PCF and could proceed from a congenital disorder of the cephalic mesoderm of the parachordal plate or occur later in the infancy because of premature stenosis of the sphenooccipital synchondrosis.

Transcranial resection of a large sinonasal juvenile psammomatoid ossifying fibroma.

INTRODUCTION: Juvenile psammomatoid ossifying fibroma (JPOF) is a benign but potentially locally aggressive fibroosseous lesion predominantly arising in the paranasal sinuses in children and young adults. Intracranial extension is rare but occurs sometimes. In such cases, tumor resection may often require the combination of neurosurgical and facial approaches. Histological diagnosis remains a challenge because the lesion can be easily mistaken for another fibroosseous lesion or for a meningioma. CASE REPORT: We report the case of a 12-year-old boy with a JPOF arising from the right paranasal sinuses and extension towards the anterior skull base and the orbit. Despite the tumor had eroded through nasal septum, medial orbit wall, and right maxilla, it could be entirely removed performing an extended frontobasal approach via a bifrontoorbital craniotomy, obviating the need for a transfacial approach. CONCLUSION: Radiologically and histologically, the lesion could be mistaken either for a meningioma or another type of ossifying fibroma. Histological aspects and alternative surgical approaches to these rare entities are discussed.

Fractionated stereotactic radiotherapy treatment of cavernous sinus meningiomas: a study of 100 cases.

PURPOSE: We discuss our experiences with fractionated stereotactic radiotherapy (FSR) in the treatment of cavernous sinus meningiomas. METHODS AND MATERIALS: From 1995 to 2006, we monitored 100 patients diagnosed with cavernous sinus meningiomas; 84 female and 16 male patients were included. The mean patient age was 56 years. The most common symptoms were a reduction in visual acuity (57%), diplopia (50%), exophthalmy (30%), and trigeminal neuralgia (34%). Surgery was initially performed on 26 patients. All patients were treated with FSR. A total of 45 Gy was administered to the lesion, with 5 fractions of 1.8 Gy completed each week. Patient treatment was performed using a Varian Clinac linear accelerator used for cranial treatments and a micro-multileaf collimator. RESULTS: No side effects were reported. Mean follow-up period was 33 months, with 20% of patients undergoing follow-up evaluation of more than 4 years later. The tumor control rate at 3 years was 94%. Three patients required microsurgical intervention because FSR proved ineffective. In terms of functional symptoms, an 81% improvement was observed in patients suffering from exophthalmy, with 46% of these patients being restored to full health. A 52% improvement was observed in diplopia, together with a 67% improvement in visual acuity and a 50% improvement in type V neuropathy. CONCLUSIONS: FSR facilitates tumor control, either as an initial treatment option or in combination with microsurgery. In addition to being a safe procedure with few side effects, FSR offers the significant benefit of superior functional outcomes.

Intracranial teratomas in children: the role and timing of surgical removal.

OBJECT: In this study, the authors report their experience with the surgical treatment of intracranial teratomas with an emphasis on the indications for delayed resection after oncological treatment. METHODS: The authors retrospectively reviewed the cases of 14 children with intracranial teratomas. The mean age at diagnosis was 10.5 years (range 2 days-18 years), and 11 patients were male. The final histological analysis revealed pure mature teratoma in 5 cases, mixed teratoma with germinoma in 3 cases, and nongerminomatous malignant germ cell tumor in 6 cases. Thirteen patients underwent tumor resection, and these patients were divided into 2 subgroups according to the timing of surgery. In Group A, 10 patients underwent resection as the primary treatment because no tumor markers were detected in 4 patients, a teratomatous component was revealed on biopsy sampling in 3 patients, and a large tumor volume in 3 patients. In Group B, 3 patients underwent removal of residual pure mature teratoma after oncological treatment. RESULTS: Seven of the 8 patients (87.5%) with pure mature teratomas or with mixed teratoma and germinoma are currently alive (mean follow-up of 9 years); the eighth patient died of postoperative meningitis. Two of the 6 patients (33%) with mixed nongerminomatous malignant germ cell tumors died of tumor progression regardless of the timing of surgery. CONCLUSIONS: The results of this study support the belief that microsurgical removal is the only effective treatment for intracranial teratomas. Surgery may be performed as the primary therapy when there is evidence of a noninvasive teratoma, and as a secondary therapy if there is only a partial response to neoadjuvant therapy or if progression is observed in mixed malignant germ cell tumors.

Intramedullary spinal cord cavernous angioma in children: case report and literature review.

INTRODUCTION: Intramedullary cavernous angiomas (ImCA) of the spinal cord are very uncommon malformations especially in the pediatric population where only ten cases have yet been reported within the available literature. CASE REPORT: In this paper, the authors report the case of a 12-year-old girl presenting with a T11 level hematomyelia because of a cavernous angioma. Microsurgical excision was performed with good clinical outcome and no magnetic resonance imaging evidence of residual cavernoma 30 months later. DISCUSSION: Despite the small number of cases reported in children, this one contributes to the literature identifying special features of presentation and management of ImCA for pediatric patients. Because a higher risk of recurrent bleeding has been demonstrated for ImCA, with dramatic clinical consequences, microsurgical removal remains the only definitive treatment.

Cervical tumoral calcium pyrophosphate dihydrate deposition disease 28 years after suboccipital craniotomy: case report.

OBJECTIVE: To describe a rare case of tumoral cervical chondrocalcinosis that appeared 28 years after the patient had undergone suboccipital craniotomy. CLINICAL PRESENTATION: A 42-year-old woman suffered from cervicalgia associated with a firm mass at the occipitocervical region. Plain x-ray and computed tomographic and magnetic resonance images revealed a calcified lesion in a scar from a previous suboccipital craniotomy. INTERVENTION: The patient underwent tumorectomy and histopathology, which revealed an exuberant tumoral chondrocalcinosis. Laboratory test results revealed no secondary cause for the chondrocalcinosis. CONCLUSION: Identification of chondrocalcinosis beyond the cervical region is very rare. Localization of chondrocalcinosis in a scar from a previous suboccipital craniotomy has not been previously reported. Surgery appears to be the treatment of choice for this form of chondrocalcinosis.

Treatment of pituitary adenomas by fractionated stereotactic radiotherapy: a prospective study of 110 patients.

PURPOSE: To optimize and reduce the toxicity of pituitary adenoma irradiation by assessing the feasibility and effectiveness of fractionated stereotactic radiotherapy (FSR). METHODS AND MATERIALS: Between 1990 and 1999, 110 consecutive patients, 47 with a functioning adenoma, were treated according to a strategy of either early surgery and FSR (n = 89) or FSR only (n = 21). Of the 110 patients, 75 had persistent macroscopic tumor and 47 persistent hormonal secretions; 15 were treated in the prophylactic setting. The linear accelerator-delivered dose was 50.4 Gy (5 x 1.8 Gy weekly), with a 2-mm safety margin. RESULTS: After a minimal follow-up of 48 months, only 1 patient had developed progression. Of the 110 patients, 27 (36%) had a complete tumor response, 67 (89.3%) had an objective tumor response, 20 (42%) had a hormonal complete response, and 47 (100%) had a hormonal objective tumor response. The proportion of patients without a complete tumor response, objective tumor response, complete hormonal response, and objective hormonal response was 85.1%, 62%, 83%, and 59.3% at 4 years and 49.3%, 9%, 59.3%, and 10.6% at 8 years, respectively. The sole unfavorable predictive factor was preoperative SSE >20 mm for tumor response (p = 0.01) and growth hormone adenoma for the hormonal response (p <0.001). No late complications, except for pituitary deficiency, were reported, with a probability of requiring hormonal replacement of 28.5% and 35% at 4 and 8 years, respectively. Nonfunctioning status was the sole unfavorable factor (p = 0.0016). CONCLUSIONS: Surgery plus FSR is safe and effective. FSR focused to the target volume seems more suitable than standard radiotherapy, and standard fractionation reduces the risk of optic neuropathy sometimes observed after single-dose radiosurgery. Therefore, FSR allows us to consider combined transrhinoseptal surgery and early radiotherapy, with a curative goal without patient selection.