Hypofractionated radiotherapy followed by adjuvant chemotherapy with temozolomide in elderly patients with glioblastoma.

OBJECTIVES: The optimal treatment for elderly patients (age >70 years) with glioblastoma (GBM) remains controversial. We conducted a prospective trial in 43 consecutive elderly patients with GBM treated with hypofractionated radiotherapy (RT) followed by adjuvant temozolomide. PATIENTS AND METHODS: Forty-three patients 70 years of age or older with a newly diagnosed GBM and a Karnofsky performance status (KPS) > or = 60 were treated with hypofractionated RT (6 fractions of 5 Gy each for a total of 30 Gy over 2 weeks) followed by up to 12 cycles of adjuvant temozolomide (150-200 mg/m(2) for 5 days during each 28 day cycle). The HRQOL was assessed with the EORTC Quality of Life Questionnaire C30. The primary endpoint was overall survival (OS). Secondary endpoints included progression free survival (PFS), toxicity and quality of life. RESULTS: The median OS was 9.3 months and the median PFS was 6.3 months. The 6 and 12 month survival rates were 86% and 35%, respectively. The 6 and 12 month PFS rates were 55% and 12%, respectively. In multivariate analysis KPS was the only significant independent predictive factor of survival (P = 0.008). Neurological deterioration occurred during or after RT in 16% of patients and was resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 28% of patients during the adjuvant chemotherapy treatment with temozolomide. The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time. CONCLUSIONS: Hypofractionated RT followed by temozolomide may provide survival benefit maintaining a good quality of life in elderly patients with GBM. It may represent a reasonable therapeutic approach especially in patients with less favourably prognostic factors.

How to set up a microsurgical laboratory on small animal models: organization, techniques, and impact on residency training.

Microsurgical training is mandatory for the optimal education of modern neurosurgeons. Even though this is a widely acknowledged statement and a lot of institutions around the world practice training in laboratory, the recent literature lacks tip and tricks on how to start a laboratory from scratch, what would be a convenient anesthesia, and what kind of exercises are appropriate. We present our experience in 16 microsurgical training courses settled up at our institutions. Two hundred eleven rodents were dissected. We will describe the organization of the laboratory and of the training courses and we will discuss its practical impact on the residency program.

Postoperative spondylodiscitis from Aspergillus fumigatus in immunocompetent subjects.

The authors describe a case of spondylodiscitis from Aspergillus fumigatus which occurred subsequent to surgery for lumbar disc herniation in a non-immunodepressed patient. The results obtained by combined medical and surgical treatment are discussed.

Fronto-temporo-orbito-zygomatic approach and variants. Surgical technique and indications.

AIM: In the last decade, development and refìnement of skull base surgery have widened the surgical options available for treatment of mtracramal lesions. Despite the enormous advances made m microsurgical technique, the bony phase is still extremely important for achievmg optimal exposure of vascular and tumoral skull base lesions. The role of anterolateral approaches for such lesions is discussed. METHODS: We collected 87 consecutive patients with 74 neoplasms and 13 vascular lesions involving the floor of the antenor and/or middle cranial fossae, cavernous sinus, orbit, petrous bone, clivus, parasellar region and infratemporal fossa operated throughout 8 and a half years by means of an anterolateral approach and we evaluated the results obtained employing different craniotomies. RESULTS: To simplify the parameters for evaluation of outcome, we considered 2 main aspects: comparison between pre- and postoperative neurological status and the extent of tumour removal on MR imaging. For vascular lesions, we took into consideration the neurological outcome and the successful clipping of the aneurysm or disappearance of the AVM (l case) on postoperative angiography. Satisfactory surgical results were obtained with each type of craniotomy employed (fronto-teniporo-orbito-zygomatic, fronto-temporo-orbital, fronto-temporo-zygomatic, fronto-orbito-zygomatic). CONCLUSION: On the whole, surgical results were satisfactory. By deliberately excluding the microsurgical aspects of the lesions treated, we can observe that the fronto-temporo-orbito-zygomatic approach is principally indicated for lesions requiring a multidirectional approach such as spheno-petro-clival tumours, aneurysms of the basilar tip and intracavemous lesions while the fronto-temporo-orbital approach proved excellent for more medial lesions such as meningiomas of the luberculum sellae and cramopharyngiomas. The fronto-temporo-zygomatic approach is our 1(st) choice for neoplasms involving the Gassenan ganglion and the intratemporal fossa. For lesions of the orbital apex, a fronto-orbito-zygomatic approach can be successfully employed. Introduction of these approaches is relatively recent but promises a further refinement of their indications and surgical technique aimed at mimmismg postoperative morbidity.

Atypical tentorial meningioma 30 years after radiotherapy for a pituitary adenoma.

Although the human central nervous system used to be considered relatively resistant to the carcinogenic action of ionizing radiation, several lines of evidence now document a high incidence of secondary tumors in irradiated patients. The numerous reports of radiation-induced cerebral meningiomas generally distinguish those induced by high-dose radiation from those induced by low-dose radiation. We describe the case of patient who underwent subtotal resection of a chromophobe pituitary adenoma at the age of 18 years, who was successively treated by conventional fractionated radiotherapy with gamma rays emitted by a source of 60Co until a total dose of 41 Gy. Over the next 30 years the patient experienced all the known late effects of radiation, including panhypopituitarism, cranial-nerve deficits (II, III and VI), massive radiation necrosis involving the left cerebral hemisphere and causing right hemiparesis and aphasia and, ultimately, an atypical tentorial meningioma with early recurrence after total resection.

Cerebral hemodynamics on MR perfusion images before and after bypass surgery in patients with giant intracranial aneurysms.

BACKGROUND AND PURPOSE: Preoperative assessment of the anatomy and dynamics of cerebral circulation for patients with giant intracranial aneurysm can improve both outcome prediction and therapeutic approach. The aim of our study was to use perfusion MR imaging to evaluate cerebral hemodynamics in such patients before and after extraintracranial high-flow bypass surgery. METHODS: Five patients with a giant aneurysm of the intracranial internal carotid artery underwent MR studies before, 1 week after, and 1 month after high-flow bypass surgery. We performed MR and digital subtraction angiography, and conventional and functional MR sequences (diffusion and perfusion). Surgery consisted of middle cerebral artery (MCA)-internal carotid artery bypass with saphenous vein grafts (n = 4) or MCA-external carotid artery bypass (n = 1). RESULTS: In four patients, MR perfusion study showed impaired hemodynamics in the vascular territory supplied by the MCA of the aneurysm side, characterized by significantly reduced mean cerebral blood flow (CBF), whereas mean transit time (MTT) and regional cerebral blood volume (rCBV) were either preserved, reduced, or increased. After surgery, angiography showed good canalization of the bypass graft. MR perfusion data obtained after surgery showed improved cerebral hemodynamics in all cases, with a return of CBF index (CBFi), MTT, and rCBV to nearly normal values. CONCLUSION: Increased MTT with increased or preserved rCBV can be interpreted as a compensatory vasodilatory response to reduced perfusion pressure, presumably from compression and disturbed flow in the giant aneurysmal sac. When maximal vasodilation has occurred, however, the brain can no longer compensate for diminished perfusion by vasodilation, and rCBV and CBFi diminish. Bypass surgery improves hemodynamics, increasing perfusion pressure and, thus, CBFi. Perfusion MR imaging can be used to evaluate cerebral hemodynamics in patients with intracranial giant aneurysm.

Cavernous angiomas of the nervous system in Italy: clinical and genetic study.

We performed a clinical and genetic study of patients affected by cavernous angiomas (CA) of the nervous system. We examined initial signs and symptoms in sporadic and familial cases. We obtained clinical, neuroimaging and genetic data on 15 Italian patients with CA of the nervous system with positive, doubtful or apparently negative family history. Genetic markers surrounding three different gene regions (7q, 3q and 7p) were analysed. In one small family, genetic linkage was consistent with all chromosome loci. In another family with the unusual association of cerebral and spinal CA, linkage with chromosome 7q and, likely, 7p was excluded, while linkage with locus 3q was possible. Our results indicate that Italian families with CA may show genetic heterogeneity. Non-specific and subtle onset symptoms hide the presence of CA within families. Patients with multiple CA may have silent cerebral lesions confirming the low penetrance of clinical signs in spite of radiological ones.

Treatment of aneurysms unsuitable for clipping or endovascular therapy.

A small percentage of aneurysms cannot be treated by traditional techniques. The majority of these are giant aneurysms, whose dimensions exceed 2.5 cm, which are particularly difficult to treat because of their anatomical characteristics. Clinically, they may present with compressive, ischemic or hemorrhagic symptoms. Treatment of intracavernous aneurysms and those of the pre- and intrapetrous segment of the internal carotid artery represent a challenge for the neurosurgeon and on occasion may not be suitable for clipping or endovascular techniques. This is true for aneurysms without a well-defined neck and fusiform aneurysms, for which extra-intracranial bypass using a graft of saphenous vein plays a fundamental role. The method used for bypass depends on whether there is sufficient collateral flow. The authors emphasize that it is not possible to identify patients who can be submitted to therapeutic occlusion of the internal carotid artery without the risk of late ischemic attacks or de novo aneurysm formation.

Total removal of an intramedullary cavernous angioma by transthoracic approach.

Intramedullary cavernous angiomas are rare vascular malformations; all published cases have been surgically approached posteriorly by standard laminectomy. We describe the case of a 63-year-old man with an intramedullary cavernous angioma, anteriorly located in the thoracic spinal cord. The angioma was operated on by transthoracic approach and totally removed.

[Neurinomas and ependymomas of the cauda equina. A review of the clinical characteristics]. / Neurinomi ed ependimomi della cauda equina. Revisione delle caratteristiche cliniche.

A retrospective review of 603 cases of intradural benign tumors of the cauda equina are presented (283 schwannomas and 320 ependymomas). For each tumor, the clinical course and long-term postoperative results were analyzed: it emerged that differential diagnosis between neurinomas and non tumoral lesions is not possible if based on clinical findings alone and that neuroradiological diagnosis is more accurate when MRI is employed. Long-term prognosis of neurinomas was always favourable, while in the ependymomas, early diagnosis gives excellent results because prognosis is apparently directly correlated to the length of preoperative clinical history.

Gangliogliomas of the cerebral hemispheres. Report of 14 cases with long-term follow-up and review of the literature.

This retrospective study focuses on 14 patients with ganglioglioma of the cerebral hemispheres who received surgical treatment in the Neurosciences Department/Neurosurgery of "La Sapienza" University of Rome between 1953 and 1990. The data are analyzed together with those on 98 published cases of ganglioglioma confined to the cerebral hemispheres. These tumours have no sex preference but a decided preference for the young (mean age 18 years). They are characterized by a history of epilepsy often of long standing and sometimes refractory to drugs. The most frequent site is the temporal lobe (61%). At operation the tumour proved to be solid in 52% of cases and the satellite cyst at the tumour wall in 48%. Removal was total in 65% of cases. Even after subtotal removal, the prognosis is good in terms both of survival and of seizure control. Radiotherapy seems to have no role in the treatment of these tumours.

Brain oedema and intracranial hypertension treatment by GLIAS.

The authors present their results regarding the use of a buffered solution of glycerol 30%-sodium ascorbate 20% (GLIAS) for the treatment of brain oedema and intracranial hypertension. GLIAS was perfused intravenously in 80 patients with several types of brain oedema. In every patients serum and urinary osmolarity, diuresis, main blood and urine parameters, and ICP were monitored. Following GLIAS infusion an increase in plasma osmolarity was observed, changing the average basal value plus 13.4% after 15 min., 10.5% after 30'. At the same time there was a reduction of ICP and improvement in cerebral compliance. In each case there was a decrease in intracranial hypertension and brain oedema without significant collateral effects.

Small aneurysm clips for surgery of neck vessels.

Surgery of the internal carotid artery and the extracranial vertebral artery is of a fundamentally preventive nature, and justifiable when intra and postoperative complications (intraoperative stroke, postoperative vessel occlusion, postoperative TIA and/or stroke) remain within very low limits (less than 5% according to major case-series'). To minimize damage to the arterial wall that could cause vessel occlusion and even neurological damage, the authors propose the use of intracranial aneurysm clips for temporary closure of the neck vessels, explaining the methods used for selection of these clips.

Primary intracranial lymphomas.

We present 20 cases of primary intracranial lymphoma and review the most important published series on this subject. The clinical patterns and the differential diagnosis from other intracranial space-occupying lesions on the CT and angiographic evidence are discussed. Surgical treatment was given in 19 of our cases, followed in 17 cases by radiotherapy and in 4 by chemotherapy. One patient was treated by a ventriculo-peritoneal shunt. The effectiveness of the various modalities of treatment is discussed in the light of survival.

Stenosis of one carotid artery with occlusion of the contralateral carotid.

23 patients with unilateral internal carotid artery stenosis (greater than 70%) and contralateral internal carotid artery occlusion in the neck are reported. The symptoms are referable to the side of the occlusion in 13 cases (57%), to the side of stenosis in 7 cases (30%) and non-localizing in 3 cases (13%). All 23 patients had a carotid endarterectomy performed on the side of the stenotic lesion. There was no operative mortality. Late neurological symptomatology after surgery was referable to the side of stenosis in 13% and to the side of occlusion in 9%. The authors consider that, in cases of significant stenosis (greater than 70%) of an internal carotid artery with a contralateral occlusion, preference should always be given to end-arterectomy of the stenotic side, reserving extra-intracranial by-pass of the occluded side for patients who remain symptomatic after endarterectomy of the stenotic side.

Primary chiasmatic lymphoma.

We report a case of primary cerebral lymphoma in an unusual site, the chiasma, and with a unique combination of symptoms. We review the salient published data on lymphomas in this site.

Multiple intracranial meningiomas.

The authors report 14 cases of multiple intracranial meningiomas representing 1.1% of all meningiomas operated on at their hospital in the past 35 years. Differentiation of multiple meningiomas, especially from meningiomatosis, must be strict. Since the introduction of computerized tomography scanning, the frequency of these cases has risen from 0.58% to 4.5% in the authors' meningioma series. Despite the multiplicity of sites, multiple meningiomas do not differ in prognosis from benign solitary meningiomas.

Neurological deficits secondary to spinal deformities: their treatment and results in 13 patients.

We report the results of surgical treatment in 13 patients operated on for compression of the spinal cord secondary to kyphosis or kyphoscoliosis between 1977 and 1985. In every case, an anterior decompression of the cord by transthoracic or thoracoabdominal route was followed in the same operation by anterior stabilization. Posterior fusion with Harrington's instrumentation was performed 15-20 days later. Neurological recovery was complete in 8 patients (61.5%) and partial in 4 (30.7%), while 1 patient died (7.6%). We review the relevant published work.

Odontoid fractures: conservative treatment and halo device in 6 young patients.

Six patients under the age of 40 with fractures of the odontoid process (4 with Anderson type III and 2 with type II) were treated conservatively by immobilization in a halo device for 14-16 weeks. The indications for surgical and conservative treatment are discussed. Follow-up from 1 to 4 years.