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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) ≥ 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/m2 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.

Transsphenoidal surgery (TSS) is a well recognised treatment for secreting pituitary adenomas, however a very wide variation of clinical outcomes and recurrence rates has been reported, depending on the different criteria used to define the cure. We reported the clinical outcome of a large series of patients operated on for a secreting pituitary adenoma according to the most recent stringent criteria of biochemical remission nowadays accepted. One hundred and twenty-five consecutive patients with a secreting pituitary adenoma (42 PRL-, 67 GH- and 16 ACTH-secreting adenomas) who were operated on by the two same neurosurgeons were considered for the study. Biochemical remission of disease was achieved in 56% of patients; 78% for patients with microadenoma and 47% for patients with macroadenomas, respectively. No cases of mortality or major immediate postoperative complications were observed. Tumour size, high hormone levels and dural invasion were significantly correlated to a poor surgical outcome. The recurrence rates ranged between 0 and 24%, being higher for PRL-secreting tumours. In conclusion, TSS is safe and effective in secreting pituitary tumours. It is still the first treatment for GH- and ACTH-secreting adenomas, whereas in patients with prolactinomas, surgery should be reserved for cases of resistance or intolerance to dopamine agonists.

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.

With the aim of understanding better the behaviour of an uncommon lesion such as the choroid plexus papilloma, we have analysed a surgical series of 33 cases operated on at the Neurosurgical Department, University of Rome "La Sapienza", between 1955 and 1992 and have reviewed the relevant literature. Our results support the view that a radical resection of these lesions, which if removed entirely, carry a very good prognosis. The hydrocephalus should be treated only if persistent. Adjuvant treatment such as radiotherapy and chemotherapy should be reserved for specific cases.

We report a retrospective study conducted on 40 patients with neurinoma of the cauda equina, assessing the clinical features and treatment. Neurinomas are clinically indistinguishable from other tumours localized in the same region. It is possible, but not simple, to differentiate neurinoma of the cauda equina from more common lumbar disc herniations. In the early stage, neurinomas provoke sciatic pain that is unilateral and monoradicular, worsened in decubitus and hard to define, whereas in the later stage pain becomes bilateral, polyradicular and is mostly accompanied by motor and sensory disturbances. Moreover, Lasegue's sign was often absent. Therapeutically, total removal of the tumour seems to be the most appropriate form of treatment given that even the sacrifice of a root does not worsen any pre-existing neurological deficit.

A series of 28 ependymomas arising in the filum terminale was divided into two groups based on the presence/absence of connections with the conus medullaris and/or roots of the cauda equina. Group A comprised ependymomas having no connections with the contiguous structures and group B those either infiltrating or adhering to such structures. Factors having a positive influence on the prognosis (risk of recurrence) were: 1) clinical history under one year (p

We report a series of 41 patients with multiple intracranial aneurysms, analyzing them by type of surgical treatment and prognosis. We compare our findings with those of the largest published series and draw conclusions regarding the most appropriate treatment. The upshot would seem to be that morbidity and mortality depend chiefly on whether the aneurysms are bilateral or unilateral and on the patient's pre-operative status.

This retrospective study was undertaken to assess the stability of the cervical spine after fixation with acrylic wire implants. Of the 44 patients with various pathological conditions of the cervical spine selected for this treatment in the course of 20 years, 36 were considered suitable for long-term follow-up evaluation. In 30 cases (83%) the stability of the spine was rated good. It is concluded that the acrylic-wire combination is a valuable surgical option in certain conditions i.e. old age, short life expectancy, poor general health, mental disease, in which long confinement in bed or in orthopaedic appliances is poorly tolerated.

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.

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-peritonal shunt. The effectiveness of the various modalities of treatment is discussed in the light of survival.

Aim: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on "anatomo–electro–clinical correlations". Methods: All consecutive patients with suspected TLE and seizure history

Criteria to define the biochemical remission of acromegaly following surgery have changed over the years, and the current use of stringent criteria needs a critical re-evaluation of the surgical results. On the other hand, few data are currently available concerning the possible impact of pituitary surgery on the quality of life of operated acromegalic patients. In this prospective study, we wished to evaluate the initial outcome and long-term recurrence rate in a large series of acromegalic patients operated on by transsphenoidal surgery (TSS), to carefully analyse predictive factors for surgical outcome and to point out possible additional effects of surgery in these patients. Ninety-two out of 98 operated patients could be considered for follow-up. Biochemical remission was strictly defined as plasma GH levels 10 ng/ml were independent negative predictors. Mortality was 0% and the overall complication rate was about 10%. Pituitary function worsened in five patients but improved in 16 out of 30 patients with preoperative pituitary defects. No recurrence was observed during a median follow-up of about 8 years. We conclude that TSS is able to achieve a biochemical remission in more than half of acromegalic patients, and that the current criteria for remission seem to indicate a cure in most cases.

Among the transcription factors involved in pituitary ontogenesis and physiology, basic helix-loop-helix (bHLH) have been poorly studied. Members of bHLH family include NeuroD1 and ASH1, both involved in neuroendocrine differentiation. We evaluated their mRNA expression patterns, by semi-quantitative RT-PCR analysis (sq-RT-PCR) and/or Northern blot, in a series of 33 pituitary adenomas (PA), anterior pituitaries, and pituitary cell lines. Immunohistochemistry for NeuroD1 was also performed in 25 PA. Low levels of NeuroD1 were observed in normal pituitaries and in the somatomammotroph cell lines GH3/GH4C1, contrasting with high levels in corticotroph AtT20 cells. NeuroD1 mRNA was widely expressed in PA (82%), with measurable levels found especially in those derived from Pit-1 independent lineages, i.e. corticotroph (5/5) and clinically non-secreting (CNS) adenomas (9/11). According to sq-RT-PCR analysis, overexpression of NeuroD1 compared to normal pituitaries was frequent. Variable nuclear NeuroD1 immunopositivity was also present in about 70% of studied cases. ASH1 mRNA was widely detected in normal pituitaries, in all tumour cell lines and in most PA (84%), with measurable levels in corticotroph (5/5) and CNS (9/11) adenomas, and in a significant subset of PA derived from Pit-1 dependent lineages (9/16). We conclude that: a) NeuroD1 is differentially expressed in PA and its possible ontogenetic and/or pathogenetic implications in non-corticotroph PA are discussed; b) ASH1 is a neuroendocrine marker whose expression is largely conserved in normal and neoplastic pituitary cells.

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.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.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).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.

Patients older than 65 years represent 3-5% of all acromegalic patients. The old age of the patients and the higher incidence of cardiovascular and metabolic complications related to acromegaly could increase the intra- and peri-operative risk, so that medical treatment is usually recommended as a therapy of choice. The aim of this retrospective study was to investigate the impact of transsphenoidal surgery in a series of 22 elderly patients with active acromegaly, with special regard to anaesthesiological risk, peri-operative complications, and clinical outcome. Despite an increased anesthesiological risk being present in 16/22 patients, no complication occurred during surgery. Similarly, no post-operative mortality or major complications were observed. Biochemical cure, defined at 6 months by glucose-suppressed plasma GH levels below 1 ng/ml and normal age-corrected IGF-I value levels, was achieved in 68% of patients and no recurrence of disease was observed in the subsequent follow-up (mean 5.2+/-2.1 years). A significant cardiovascular improvement was observed in cured patients, with a decrease of left ventricular mass index (91.3+/-20.1 vs 115.9+/-15.0 g/m(2); P0.005), as measured by echocardiography, as well as a slight but significant decrease of systolic and diastolic blood pressure values (130.0+/-12.1 mmHg vs 137.6+/-13.5 mmHg P0.05; and 84.2+/-6.4 mmHg vs 88.8+/-7.5 mmHg P0.05, respectively). A significant post-operative improvement of glucose tolerance was also observed in this group. We conclude that transsphenoidal surgery, if well planned and carefully performed, is safe and able to induce a significant cardiovascular and metabolic improvement even in elderly acromegalic patients.

The number of epidermal growth factor (EGF) binding sites was determined by competitive binding assays in a series of 46 pituitary macroadenomas. A single concentration of 125I-EGF (1 nM) was used for all experiments. In four cases, a displacement curve was obtained by adding increasing concentrations of cold EGF, and Scatchard analysis showed the presence of two classes of EGF binding sites, with Kd1 = 0.62 +/- 0.23 nM and Kd2 = 53.8 +/- 8.2 nM for the high- and low-affinity binding sites respectively. The distribution of EGF binding sites was studied in 42 cases by a single-point assay, in the presence and in the absence of a 100-fold cold EGF excess. A non-parametric distribution of EGF binding sites was observed (median 10.2 fmol/mg membrane protein, range 0.0-332.0). EGF-receptor positivity, defined as EGF binding > or = 10.0 fmol/mg protein, was observed in 23 samples (54.8%), especially in prolactinomas (76.5%, P < 0.05 vs other tumors taken together) and in gonadotrope adenomas (62.5%). EGF binding was higher in invasive than in non-invasive adenomas (median: 12.8 vs 0.0 fmol/mg membrane protein, P = 0.047), and especially in adenomas invading the sphenoid sinus (median 26.7 fmol/mg membrane protein, P = 0.008 vs other adenomas). EGF binding also tended to increase with the grade of supra/extrasellar extension according to Wilson (P = 0.15). Sex steroid receptors (SSRs) were simultaneously determined in both cytosolic and nuclear fractions of 31 pituitary adenomas. Estrogen and progesterone receptors were determined by an enzyme-linked immunoassay and androgen receptors by a competitive binding assay with [3H]methyltrienolone. No correlation could be found between EGF binding and either the gender and gonadal status of the patients, or the expression of SSRs by the adenomas. We conclude that the EGF family of growth factors may play a role in the evolution of a significant subset of human pituitary adenomas, especially in their invasiveness, and that a high EGF binding capacity may represent an additional marker of aggressiveness for these tumors. Sex steroids do not appear to have a significant role in the regulation of EGF binding in vivo in these tumors.

Glioblastoma multiforme (GBM) is a diffuse brain tumor characterized by high infiltration in the brain parenchyma rendering the tumor difficult to eradicate by neurosurgery. Efforts to identify molecular targets involved in the invasive behavior of GBM suggested ion channel inhibition as a promising therapeutic approach. To determine if the Ca 2+ -dependent K + channel KCa3.1 could represent a key element for GBM brain infiltration, human GL-15 cells were xenografted into the brain of SCID mice that were then treated with the specific KCa3.1 blocker TRAM-34 (1-((2-chlorophenyl) (diphenyl)methyl)-1H- pyrazole). After 5 weeks of treatment, immunofluorescence analyses of cerebral slices revealed reduced tumor infiltration and astrogliosis surrounding the tumor, compared with untreated mice. Significant reduction of tumor infiltration was also observed in the brain of mice transplanted with KCa3.1-silenced GL-15 cells, indicating a direct effect of TRAM-34 on GBM-expressed KCa3.1 channels. As KCa3.1 channels are also expressed on microglia, we investigated the effects of TRAM-34 on microglia activation in GL-15 transplanted mice and found a reduction of CD68 staining in treated mice. Similar results were observed in vitro where TRAM-34 reduced both phagocytosis and chemotactic activity of primary microglia exposed to GBM-conditioned medium. Taken together, these results indicate that KCa3.1 activity has an important role in GBM invasiveness in vivo and that its inhibition directly affects glioma cell migration and reduces astrocytosis and microglia activation in response to tumor-released factors. KCa3.1 channel inhibition therefore constitutes a potential novel therapeutic approach to reduce GBM spreading into the surrounding tissue. © 2013 Macmillan Publishers Limited All rights reserved.

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.

✓ Forty-one patients with brain lesions underwent brain biopsy using either a computerized tomography (CT)-guided stereotactic approach or an ultrasound-guided technique. The cases were selected according to location and size of the mass lesion. Lesions 15 mm or less in diameter and those in the posterior fossa were biopsied by a CT-guided stereotactic technique (18 patients). Supratentorial lesions with a diameter larger than 15 mm were approached using ultrasound guidance (23 patients). These criteria for procedure selection provided a diagnostic yield of 94% for the CT-guided procedures and 91% for those guided by ultrasound. Safety for the two procedures was similar. The ultrasound procedure was more rapid, simpler, and less costly to perform. It is concluded that, with the protocol described, CT-guided stereotactic procedures could be reserved for cases in which absolute accuracy is mandatory.

A series of 42 cases of monstrocellular brain tumour (MBT) who received surgery over a 34 year period is reviewed with the aim of gaining more understanding of the biology of this oncotype. A case of benign pleomorphic xanthoastrocytoma was identified among the cases and is discussed in another paper. In this series, as in most others taken from the literature, MBTs were more frequent in young subjects (55% were under 50 years of age and 17% were children) and presented as a superficially located (63%), often sharply circumscribed (42%) mass. The mean survival time for 24 patients treated by surgery and radiotherapy (RT) was 57 weeks compared to 32 weeks for 12 treated by surgery alone (p less than 0.02). Patients younger and older than 50 years showed the same survival and the slightly better course of children did not reach statistical significance. Besides postoperative RT, the only other factor that showed a significantly positive influence on survival was the presence of a definite lymphocytic infiltration (LI) in the tumour (p less than 0.05). This result confirms our previous study on the prognostic influence of LI in glioblastoma (GB). Actually, we noted that the prolonged survival of both MBT and GB patients exhibiting a definite LI (67% and 11.5%, respectively, in the two series) was strikingly similar. We conclude that MBT is a peculiar oncotype with a probably better prognosis than GB in the majority of cases. Lymphocytes seem to play a major prognostic role and giant-monstrous cells are indirectly implicated, reasonably enhancing the host's immune response by magnifying the antigenic stimulus.

The value of spinal CT in the diagnosis of postoperative epidural scars is illustrated in 5 patients who had previously undergone surgery for lumbar disc protrusions and/or stenosis of the lumbar cana

Eight per cent of 387 acutely head-injured patients had concomitant orbitofacial injuries. Irrespective of the magnitude of brain injury, the main surgical goals in such cases treated were closure of CSF fistulas, maximizing recovery of eye movement, visual and masticatory function, and esthetic reconstruction. The strictly neurosurgical lesions should be dealt with at once because of the risk of intracranial infection. Antibiotic acrylic and antibiotic wax are valuable in such intervention. In most cases it is advantageous to treat lesions of the upper two thirds of the facial complex in the same operative session. For this reason neurosurgeons who do not have ready access to a maxillofacial specialist should be prepared to cope with the problems presented by orbitofacial injuries.

The operative results in 37 consecutive patients suffering from developmental stenosis of the lumbar spinal canal, compared with those in spondylosis and disc herniations, are discussed. The diagnostic certainty of stenosis, suspected on the bases of clinical and radiographic data, is reached only at the operating table. To judge the usefulness of the operation we have considered not only the patients' verdicts, but also the improvements in neurological signs and the appearance of new deficits. Satisfactory results are around 80%, slightly less good with stenosis than with the other causes of lumbar syndrome. Radiographic study with contrast medium is mandatory. Dimer-X has been used with very clear radiographic findings and very few complications. Operating technique is also described: a wide laminectomy with facetectomy is advised. The great importance of early physiotherapy is emphasized.

4 cases of thoracic disk protrusion were studied with spinal CT and with either plain X rays of myelography, until now the only tools for a precise diagnosis. In patients with a thoracic compression syndrome and a calcification within the canal CT alone clinches the diagnosis, as it does in cases in which the calcified material is not detectable but the clinical symptoms point to a precise lesion level. In such cases myelography is unnecessary. It should however be done first when neither the clinical symptoms nor the plain X rays indicate the level of the lesion.

The authors have reported on the prognostic value of continuous monitoring of somatosensory evoked potentials (SEP) in a survey of 25 patients who underwent carotid surgery. SEP recordings were correlated with the EEG, stump pressure (SP) values and clinical outcome. A non-cephalic reference was used for SEP recordings to allow the analysis of both subcortical and cortical components. During surgery the conduction time between SEP peaks relating to the subcortical components remained stable or showed minimum variations in all patients. During carotid clamping, SEP variations were observed in 9 out of 25 cases (36%). The application of an intraluminal shunt was accompanied by the return to normal values in 7 out of 9 patients. In the remaining two cases SEP abnormalities continued post-operatively and were accompanied by new neurological deficits. EEG changes during carotid clamping were associated with SEP modifications in 6 out of 7 cases, although they were not always correlated. Results confirm that SEP recordings provide useful data concerning the function of the CNS in anaesthetized patients and that, being sensitive to CBF changes, SEP monitoring acts as an indicator of cerebral ischaemia.

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.