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In the last few years much has been published to validate new technology in brain mapping for clinical purposes, but there have been few clinical results. In this report we describe our five-year experience in the surgical management of malignant gliomas around motor areas with an evaluation of the impact of functional magnetic resonance imaging (fMRI) plus navigator and intraoperative neurophysiology (IN). End-points were extent of removal, morbidity, and survival. Variables describing patient and tumor characteristics and treatment modalities were statistically weighted in relation to treatment outcome. Tumor depth (P = 0.01), midline shift >/=1 cm. (P = 0.05), and insular location (P = 0.001) negatively affected extent of removal, whereas IN (P < 0.001) and fMRI plus navigator (P = 0.02) contributed to increasing the rate of total removal (73\%, 71\% vs. 40\%). Postoperative motor impairment was mild and transient in a minority of cases (20\%). General complications, as defined by the Glioma Outcome Project, occurred in 23\% of cases. IN was the only factor associated with acute postoperative motor deterioration (P < 0.001). IN and age >65 years (P = 0.01) were associated with the occurrence of complications. Overall survival was significantly higher in patients operated with IN or fMRI plus navigator (P < 0.01). Comparing different surgical strategies used in the same period, we observed that supportive technologies in glioma surgery have their primary impact on the quality of resection and survival. IN led to transient motor impairment and some additional complications which did not affect functional outcome.

Purpose We performed a new phase II trial enrolling patients with newly diagnosed high-grade glioma (HGG) to test the efficacy of a weekly alternating temozolomide (TMZ) schedule after surgery and concomitant chemoradiotherapy. Methods From January 2005 to January 2007, 34 patients (21 men, 13 women; age range 30–70, mean age 53) were enrolled. There were 32 glioblastoma multiforme and two anaplastic astrocytoma. Each patient after surgery received standard concurrent chemoradiotherapy. After a 4-week break, patients were then to receive 12 cycles of 1-week-on/1-week-off TMZ, with 75 mg/m2 for the first cycle, 100 mg/m2 for the second, 125 mg/m2 for the third, and 150 mg/m2 from the fourth to the 12th. Hematological toxicity was monitored every week during concomitant chemoradiotherapy and then every 4 weeks. Results After 12 months from the end of radiotherapy, the overall survival (OS) rate was 59% (20/38), distributed as follows: 60% (18/30) for recursive partitioning analysis (RPA) class 4 patients and 33% (1/3) for RPA class 6 patients; the only RPA class 1 patient was alive and disease free at the time of writing. Median OS was 13 months [95% confidence interval (CI) 11.02–14.98 months]. Hematological toxicity was seen in six patients (18%): grade 1 neutropenia in four, grade 2 thrombocytopenia in one, and grade 4 thrombocytopenia plus grade 1 neutropenia in one. There was one case of opportunistic infection (Pneumocystis carinii pneumonitis). Conclusion The toxicity of the TMZ dose-dense regimen was very low. Results seem to be encouraging for RPA lower classes (patients with good prognostic factors).

Background: Nitrosoureas constitute the main resource of chemotherapy for glioblastoma. However, because of chemoresistance, which is intrinsic or rapidly acquired after the first administration of chemotherapy, there have been few improvements in survival. Because O6-alkylguanine-DNA alkyltransferase (AGT) is the main target for increasing cell sensitivity to the nitrosoureas, we postulated that preexposure to other alkylating agents might increase the therapeutic index of the nitrosoureas by saturating all the copies of AGT present in the tumor cells.Objective: To investigate the response rate, toxic effects, time from start of chemotherapy to progression of disease or exit from the study for any reason (TTP), and progression-free survival at 6 months (PFS-6) associated with a multidrug combination that could reverse resistance to carmustine (BCNU) through AGT depletion.Methods: We conducted a phase 2 study of patients with glioblastoma at first relapse or progression after surgery and standard radiotherapy. Patients were treated with 100 mg/m2 of procarbazine on days 1 to 5, 80 mg/m2 of BCNU on days 3 to 5, and 1.4 mg/m2 of vincristine on day 3 every 8 weeks.Results: Fifty-eight patients were enrolled in the study, and all were assessable for response and toxic effects. Six patients (10.3%) had a complete response, 11 (19%) had a partial response, and 17 (29.3%) had stable disease. The median TTP was 4.8 months; 42.3% of patients had PFS-6, and 15.4% had PFS at 12 months. Response to chemotherapy was the only significant prognostic factor for TTP. Neutropenia was grade 3 in 8.6% of patients and grade 4 in 5.2% of patients, and thrombocytopenia was grade 3 in 17.2% of patients and grade 4 in 12% of patients; hepatic and pulmonary toxic effects were grade 3 in 5.2% and 8.6% of patients, respectively.Conclusion: This regimen proved active in chemotherapy-naive patients with recurrent glioblastoma even though toxic effects were substantial.

A total of 121 patients surgically treated between 1991 and 2011 for cavernomas in critical supratentorial areas were evaluated. Anatomical location, size and the possible association with developmental venous anomalies (DVA) were assessed in each case: 43 cavernomas were in the speech area, 39 were rolandic (or peri-rolandic), 14 insular, 10 nuclear, 9 calcarine and 6 ventricular. In 49 % of the cases, the cavernoma was1.5 cm; in 6 patients, radiological growth was documented. A method of intraoperative localization was adopted in 78 cases: B-mode echography or a stereotactic guide in 22 cases, and a neuronavigation system in 56 cases; preoperative angiography was done in 22 cases. Early postoperative epilepsy (within 7 days of surgery) was observed in 15 cases. As for clinical outcome, 14 patients presented with mild symptoms (modified Rankin Scale 1-2); significant deficits occurred ex-novo in 5 patients. The presence of epilepsy at follow-up was assessed through the Maraire Scale: 44 % of patients presenting with epilepsy were free of seizures and without therapy at a mean follow-up of 4.6 years, and an additional 55 % had complete control of seizures with therapy. It is concluded that surgery is indicated in the management of cavernomas in critical supratentorial locations, with a caveat for insula and especially basal ganglia.

BACKGROUND Choroid plexus papillomas (CPPs), of the cerebellopontine angle (CPA), are a rare entity and no surgical series have been reported so far. We reviewed all the pertinent literature of 12 patients operated on in the last 20 years at our institution. METHODS All the patients were adults, ranging from 19 to 61 years. The group included 6 males and 6 females. Preoperatively, on computerized tomography (CT) ( n = 10) or magnetic resonance imaging (MRI) ( n = 4), differential diagnosis was difficult to achieve, especially with meningiomas. Hydrocephalus was disclosed in 8 cases. Angiography ( n = 11) showed tumor blush with typical vascular supply in almost half the cases. RESULTS In 6 patients a midline approach via the cerebellomedullary fissure was used; in the remaining 6 patients the retromastoid route was adopted. We found 2 "unconnected" tumors; no hilum was identified at surgery. Total tumor removal was achieved in 6 patients, predominantly in the last cases. Two patients died in the postoperative period, 3 patients had mild additional deficits, whereas 7 patients were stable or improved. All the patients were followed up for a mean period of 8.2 years. Conventional radiotherapy was carried out in 5 patients; 1 of them after tumor recurrence. Stereotactic radiotherapy was performed in 3 patients; 2 of them after recurrences. Two patients showed tumor progression and died during the follow-up. One of them presented a suprasellar metastasis and died much earlier (2 versus 7 years). CONCLUSION Careful assessment and surgical planning is accomplished with the combined information from CT, MRI, and angiography. Typical characteristics are the following: vascular supply from the choroidal arteries, ventral extension, adhesion to the brainstem, and lower cranial nerves. Nowadays, total removal of CPPs of the CPA can be achieved with acceptable morbidity and mortality. In our experience, conventional radiotherapy did not prove effective.

A case of dumbbell-shaped hypoglossal neurinoma with intra- and extracranial extension is reported. The tumour was surgically completely removed in a one-stage operation via a dorsolateral sub-occipital transcondylar approach. Clinical presentation and the role of high-resolution CT-scan, MRI and angio-MRI in diagnosis and surgical planning are discussed. We include a review of the literature concerning these rare tumours of the foramen magnum region.

A total of 121 patients surgically treated between 1991 and 2011 for cavernomas in critical supratentorial areas were evaluated. Anatomical location, size and the possible association with developmental venous anomalies (DVA) were assessed in each case: 43 cavernomas were in the speech area, 39 were rolandic (or peri-rolandic), 14 insular, 10 nuclear, 9 calcarine and 6 ventricular. In 49 % of the cases, the cavernoma was

O(6)-methylguanine DNA-methyltransferase (MGMT) promoter methylation status is a prognostic factor in newly diagnosed glioblastoma patients. However, it is not yet clear whether, and if so how, MGMT methylation status may change. Moreover, it is unknown whether the prognostic role of this epigenetic feature is retained during the disease course. A retrospective analysis was made using a database of 614 glioblastoma patients treated prospectively from January 2000 to August 2008. We evaluated only patients who met the following inclusion criteria: age > or = 18 years; performance status 0-2; histological diagnosis of glioblastoma at both first and second surgery for recurrence; postoperative treatment consisting of: (i) radiotherapy (RT) followed by adjuvant temozolomide (TMZ) until 2005 and (ii) TMZ concurrent with and adjuvant to RT after 2005; a time interval > or = 3 months between first and second surgery. MGMT status was evaluated at first and second surgery in all 44 patients (M:F 32:12, median age: 49 years, range: 27-67 years). In 38 patients (86.4%), MGMT promoter status was assessable at both first and second surgery. MGMT methylation status, changed in 14 patients (37%) of second surgery samples and more frequently in methylated than in unmethylated patients (61.5% vs 24%, P = .03). The median survival was significantly influenced only by MGMT methylation status determined at first surgery (P = .04). Significant changes in MGMT methylation status during the course of GBM occur more frequently in MGMT methylated than unmethylated cases. MGMT methylation status determined at first surgery appears to be of prognostic value; however, it is not predictive of outcome following second surgery.

This is a report of 33 consecutive cases of petroclival meningioma treated surgically at our institution over the last 10 years; there were 21 women and 12 men between the ages of 27 and 68 (mean age, 52). All patients were assessed by computed tomographic scans including coronal sections and bone algorithm studies; in most cases, digital subtraction angiography and magnetic resonance imaging were also done. The largest tumor diameter was between 2 and 3.5 cm in 14 cases, 3.5 to 6 cm in 15 cases, and over 6 cm in 4 cases. Dural attachment predominantly involved the clivus and apical petrous bone on one side only; in 14 cases, however, the tumor grew over the clivus midline or crossed the tentorial notch. Cranial nerve deficit was extant in all cases and was commensurate with tumor size. Cerebellar signs and somatic motor deficits were present in 60 and 30% of cases, respectively. The surgical approaches used were the retromastoid-retrosigmoid in 23 cases, subtemporal in 5 cases, and combined retromastoid subtemporal presigmoid in the remaining 5. Total removal was achieved in 26 cases (79%); incomplete removal occurred in 7 cases (21%). The extent of tumor removal and operative morbidity were not significantly related to tumor size. Brain stem indentation, arterial and cranial nerve encasement, and epidural invasion were the main factors that prevented total tumor removal and influenced operative morbidity. There was no intraoperative mortality, but three patients (9%) died perioperatively. In the postoperative period, most patients went through momentary neurological deterioration, chiefly due to new cranial nerve deficits. The average follow-up was 4.3 years in 27 patients; of these 17 were unchanged and 10 were improved. Before surgery, only 13 patients were self-sufficient; at long-term follow-up, another 6 had achieved independence. Our experience suggests that, even though real petroclival meningiomas still represent a formidable surgical challenge, such tumors can in most cases be removed completely with low attendant mortality and acceptable morbidity.

This article discusses the role of intracranial tumors in the etiology of spontaneous intracerebral hematomas, compared to other causes such as hypertension, aneurysm, arteriovenous malformation (AVM) or cavernoma. An analysis of cerebral tumors, with a particular oncological emphasis on intrinsic bleeding during growth and resulting in symptomatic hematoma, is presented.We analyzed 110 cases of intracranial tumor with symptomatic bleeding, accounting for 1.5% of 7373 intracranial neoplasms and 4.4% of 2514 intracerebral hematomas, surgically treated at the Department of Neurosurgery in Verona, from 1968 to 2000. The bleeding tumors comprised 36 (33%) glioblastomas, 23 (21%) metastases, 14 (13%) anaplastic gliomas, 13 (12%) low-grade gliomas, 13 (12%) meningiomas, 5 (5%) adenomas, 2 (2%) hemangioblastomas, 2 (2%) melanomas, 1 (1%) neuroblastoma and 1 (1%) pinealoblastoma.Analysis of the data of the 110 cases of tumors with symptomatic hematoma showed that there was a statistically significant correlation between the incidence of bleeding and histological groups according to the World Health Organization classification. A clinical study of these cases indicates that hematoma onset is more frequent in anaplastic gliomas (93%) and meningiomas (62%) than in other pathologies (p=0.008); meningiomas are prevalent on the left side (92%) (p=0.000); favorable bleeding factors correlate with meningioma (62%), (p=0.009). The postoperative short-term results following hematoma evacuation and tumor removal were significantly influenced only by patient age (p=0.000) and preoperative clinical condition (p=0.000).The analysis of our study population shows that the tumoral etiology of intracerebral hematomas is by no means negligible, accounting for 4.4% of 2514 hematomas operated on, and emphasizes the fact that not all bleeding neoplasms are malignant. Out of a total of 110 hemorrhagic tumors 23 (21%) were benign and 6 (5%) low-grade. The tumoral origin of cerebral hematoma is not always correctly diagnosed by non-contrast-enhanced CT and angiography, and therefore, in the presence of a hematoma with an "atypical" appearance, it is advisable to complete the diagnostic investigations with contrast-enhanced CT or MRI for the purposes of better planning surgical evacuation of hematoma and tumor removal, bearing in mind the high incidence of bleeding in benign and low-grade tumors as well as the optimal short and long-term results obtained with surgery.

Purpose To assess in a prospective trial the value of prognostic factors and the outcome of medulloblastoma in adults. Methods and materials Patients (≥18 years) with a histologic diagnosis of medulloblastoma were staged according to Chang et al. 's classification (low risk: T1, T2, T3a, M0, and no residual disease after surgery; high risk: T3b–T4, any M+ or postoperative presence of residual tumor). In low-risk patients, treatment consisted of 36 Gy to the craniospinal axis, supplemented by a local tumor dose of 18.8 Gy (total dose of 54.8 Gy). In high-risk patients, 2 cycles of “up-front chemotherapy” were delivered before the same radiation therapy, followed by maintenance chemotherapy if M1, M2, or M3 disease was present. Results Over a 12-year period, 36 evaluable patients were enrolled. Progression-free survival (PFS) at 5 years was higher in low-risk patients compared to the high-risk group: 76% ± 14% (95% confidence interval [CI] = 52%–100%) vs. 61% ± 11% (95% CI = 42%–87%). Patients with M− disease showed a significantly better outcome than M+ patients, with 75% showing PFS at 5 years vs. 45% ( p = 0.01). Conclusions The overall PFS observed is comparable to that obtained in pediatric series and suggests that a more effective therapy must be developed for high-risk patients.

Objectives: To investigate the efficacy of temozolomide (TMZ) in relationship to progression free survival at 6 months (PFS-6), median time to progression (TTP), response rate and toxicity, a phase II study was conducted in patients with recurrent glioblastoma multiforme (GBM) following surgery plus radiotherapy and a first-line regimen based on nitrosourea, procarbazine and vincristine. Methods: Forty-two patients with GBM were administered TMZ at the dose of 150 mg/m2/daily for 5 days every 4 weeks. Results: The PFS-6 and at 12 months (PFS-12) was 24% (95% Confidence Interval [CI] = 14–42%) and 8% (CI = 2–27%), respectively, with a median TTP of 11.7 weeks (CI = 9–22 weeks). The response was assessed in all 42 patients; we observed 2 complete responses (CR) (4.7%), 6 partial responses (PR) (14.3%), and 9 stable disease (SD) (21.4%), with CR+PR = 19% (CI = 7–31%). Conclusion: TMZ as a second line regimen is a valid option in patients with heavily pretreated GBM.

Surgical treatment of ventricular dilatation following severe head trauma (GCS8) remains controversial due to the difficulty to distinguish brain atrophy-related ventriculomegaly from active, symptomatic ventricular dilatation. Consequently, the reported incidence of post-traumatic hydrocephalus in literature varies greatly from 0.7-29%. The presence of ventricular dilatation following severe head trauma should be considered and demands investigation, based also on satisfactory results obtained with cerebrospinal fluid (CSP) shunting,Ninety-eight patients with post-traumatic hydrocephalus undergoing CSF shunting were selected for this study among 4,044 patients with severe head trauma treated from 1972 to 1999 at the Department of Neurosurgery at the City Hospital of Verona. Patients included 82 (84%) males and 16 (16%) women, ranging from one month to 83 years (mean age; 39 years). In 24 (24%) cases, the brain trauma lesion was single, while in 74 (76%) cases the patient suffered multiple cranio-cerebral lesions. The total number of lesions was 230 including 214 (93%) supratentorial and 16 (7%) posterior cranial fossa (PCF) lesions. Seventy-nine operations were performed on 59 (60%) patients. The onset of hydrocephalus was immediate after trauma in 14 (14%) cases, whereas a delayed onset was observed within 30 days in 44 (45%) cases, between one-four months in 30 (31%) cases and between four-six months in 10 (10%) cases. Of the 98 patients in this study, 15 were treated with an external CSF shunt and 83 underwent internal CSF shunting.Long-term results of the 15 patients with external shunts demonstrated good recovery in 13% while 87% of cases resulted in death. In the 83 cases of internal shunts, despite severe preoperative conditions (75% in coma or persistent coma), the results were as follows: good recovery in 37 (45%) patients, partial disability in nine (11%), persistent coma in 29 (35%) and death in seven (8%) cases.Post-traumatic hydrocephalus is a complication that must always be considered in cases of severe head trauma (GCS8) in young patients presenting added neurological deficits, ceased clinical improvement (ceased improvement after initial improvement), increased hypertonia, surgical flap tension or CSF accumulation. The results of this study suggest the necessity to treat post-traumatic ventricular dilatation with aggressive surgery and CSF shunting, based on favorable outcome seen even in coma and persistent coma patients.

Current neurological opinion favours the extensive surgical removal of supratentorial glioma, when feasible, without injury to normal structures. Several recent studies relate the extent of surgical resection to the length and quality of survival. Better surgical results due to microsurgical techniques and operative facilities suggest the re-evaluation of the role of surgery in the overall management of glial tumours.

OBJECTIVE: Currently, the surgical approach to olfactory meningiomas can vary depending on the size and expansion of the tumor, although surgical treatment still relies on the anterior bilateral craniotomy. Since 1989, we have use the pterional approach as a standard procedure in the treatment of 37 consecutive cases. We present our results in an attempt to contribute an alternative and valid surgical strategy for the treatment of these tumors. METHODS: Between 1989 and 1996, a series of 37 consecutive patients underwent microsurgical tumor resection using the unilateral pterional approach; all patients except one underwent operations on the right side. In 23 patients (62%), the tumor diameter measured approximately 6 cm, and the size was less than 4 cm in only 5 patients. The clinical presentation included mental dysfunction in 27 patients and visual impairment in 16 patients. The advantages of this approach are the early recognition of the posterior cerebrovascular complex, followed by a safe, rapid, and complete devascularization of the tumor and later by a favorable dissection of the capsular area from the frontal vascular branches and parenchyma. RESULTS: Total removal was achieved in all cases. There was one death unrelated to surgery. All patients presenting with mental dysfunction or with preoperative visual deficits recovered or improved. Postoperative magnetic resonance imaging confirmed complete tumor removal and demonstrated the brain parenchyma to be preserved and intact, primarily on the side opposite from the craniotomy. CONCLUSION: Our experience with the pterional approach suggests a greater role for this procedure in the treatment of olfactory groove meningiomas.

PURPOSE: A phase II study was conducted in patients with high-grade gliomas that recurred after surgery plus radiotherapy and a first-line nitrosourea-based regimen. Our aim was to investigate the efficacy of procarbazine (PCB) combined with high-dose tamoxifen in relation to tumor control, toxicity, and time to progression (TTP). PATIENTS AND METHODS: Fifty-three patients were treated with procarbazine in repeated 30-day courses at 100 mg/m2/d plus tamoxifen 100 mg/d, with a 30-day interval between courses. Thirty-four patients had been pretreated with a first-line nitrosourea-based chemotherapy regimen (group A), and 19 patients had also been pretreated with a second-line chemotherapy regimen consisting of carboplatin and teniposide (group B). Twenty-one of the patients had also been procarbazine pretreated, whereas the remaining 32 patients were not procarbazine pretreated. RESULTS: The response was assessed in 51 patients, 28 of whom had glioblastoma multiforme (GBM) and 23 of whom had anaplastic astrocytoma (AA). There were two complete responses (CR) (4%) and 13 partial responses (PR) (25.5%). The overall response rate (CR + PR) was 29.5% (SE, 6.4; 95% confidence interval [CI], 23 to 35.8). Seventeen patients (32%) had stable disease (SE, 6.2; 95% CI, 21 to 33.6). The median TTP was 13 weeks for patients with GBM and 33 weeks for patients with AA (P = .006). The median survival time (MST) was 27 weeks for patients with GBM and 57 weeks for those with AA (P = .006). CONCLUSION: Combined PCB and tamoxifen as a second-line regimen gave a reasonably high response rate in patients with heavily pretreated high-grade gliomas. However, although it resulted in an improvement in the patients' quality of life and/or performance status, it was not followed by an increased TTP or MST.

OBJECTIVE: The management of a series of 28 patients operated on for posterior fossa epidermoids is reviewed, emphasizing the need for long-term follow-up. We discuss the rationale for a comprehensive classification system that may allow the comparison of results from homogeneous series. METHODS: We grouped the tumors to differentiate the surgical management according to various tumor sites and the degree of extension. Twenty patients harbored tumors located in the cerebellopontine angle, five patients harbored tumors in the fourth ventricle, and three patients harbored tumors in the posterior fossa basal. In 17 patients, extensions of tumors outside the posterior fossa included the following regions: the suprasellar/ chiasmatic (n = 5), the parasellar/temporobasal (n = 5), and the mesencephalic/pineal (n = 7). Tumor extension was also defined by the number of regions involved. Pre- and postoperative magnetic resonance imaging and computed tomographic findings collected in 17 and 28 patients, respectively, were carefully evaluated. RESULTS: Clinical features and surgical approaches varied according to location and growth pattern. Fifty-seven percent of the tumors were completely removed. A higher total removal rate was achieved in patients with tumors confined to the primary location. One patient (3%) died in the perioperative period. Approximately half of the patients presented with transient mild focal deficit impairments resulting from the manipulation of the nervous structure over a wide area. There was a higher rate of surgical complications with fourth ventricle and mesencephalic extended cerebellopontine angle tumors. The mean follow-up period was 8.6 years. Thirty percent of the patients with subtotal removal experienced symptomatic recurrences after 8.1 years, whereas all patients with total removal were still asymptomatic. The recurrence-free survival rate was 95% at 13 years for patients with total removal compared with 65% for patients with subtotal removal. Problems of identification of tumor regrowth are discussed. CONCLUSION: By assessing posterior fossa epidermoids, we determined that location and extension play a major role in the prognosis. Our data suggest that more aggressive surgery is called for at first operation, and that a second operation should be planned when regrowth becomes symptomatic and/or tends to extend outside its original site.

In broad outline, the purpose of this chapter is first, to offer a review of past philosophies in the management of brainstem tumours, covering roughly the last half-century; next, to revisit the functional neuroanatomy of the brainstem in relation to modern neurosurgical applications; and finally, to present and discuss specific microsurgical techniques that we have used in 130 cases to date. This latter aspect is still open to much discussion and even controversy as many readers continue to believe that surgery for intra-axial brainstem tumours carries too high a risk and is of doubtful ethical justification. The most stringent opinions hold that the brainstem should be not violated even to obtain biopsy samples or perform partial removal of the tumour.

e12533 Background: Primary brainstem tumors (PBST) are the most common neoplasm of central nervous system (CNS) in children. In adults PBST is a rare disease, the incidence was reported to be 5% of...

This is a report of 33 consecutive cases of petroclival meningioma treated surgically at our institution over the last 10 years; there were 21 women and 12 men between the ages of 27 and 68 (mean age, 52). All patients were assessed by computed tomographic scans including coronal sections and bone algorithm studies; in most cases, digital subtraction angiography and magnetic resonance imaging were also done. The largest tumor diameter was between 2 and 3.5 cm in 14 cases, 3.5 to 6 cm in 15 cases, and over 6 cm in 4 cases. Dural attachment predominantly involved the clivus and apical petrous bone on one side only; in 14 cases, however, the tumor grew over the clivus midline or crossed the tentorial notch. Cranial nerve deficit was extant in all cases and was commensurate with tumor size. Cerebellar signs and somatic motor deficits were present in 60 and 30% of cases, respectively. The surgical approaches used were the retromastoid-retrosigmoid in 23 cases, subtemporal in 5 cases, and combined retromastoid subtemporal presigmoid in the remaining 5. Total removal was achieved in 26 cases (79%); incomplete removal occurred in 7 cases (21%). The extent of tumor removal and operative morbidity were not significantly related to tumor size. Brain stem indentation, arterial and cranial nerve encasement, and epidural invasion were the main factors that prevented total tumor removal and influenced operative morbidity. There was no intraoperative mortality, but three patients (9%) died perioperatively. In the postoperative period, most patients went through momentary neurological deterioration, chiefly due to new cranial nerve deficits. The average follow-up was 4.3 years in 27 patients; of these 17 were unchanged and 10 were improved. Before surgery, only 13 patients were self-sufficient; at long-term follow-up, another 6 had achieved independence. Our experience suggests that, even though real petroclival meningiomas still represent a formidable surgical challenge, such tumors can in most cases be removed completely with low attendant mortality and acceptable morbidity.

Updating a previous report, the authors offer a review of 45 patients between age 2 and 63 treated by direct surgical excision for brainstem tumours of various description. Since 1986 all candidate patients were examined by NMR imaging in addition to CT scanning, sometimes with the further addition of digital-subtraction vertebral angiography. By Epstein and McLeary's criteria, 24 of the tumours were focal, 12 were cervicomedullary and 9 were diffuse. The most frequent histological diagnosis was glioma (36 cases between low-grade astrocytoma, anaplastic astrocytoma and glioblastoma); the balance was provided by cavernoma (6 cases), haemangioblastoma (2 cases), and lipoma (2 cases). Gross total resection was achieved in 28 patients, namely all those with ependymoma or vascular tumours and 14 of 17 with low-grade astrocytoma. Resection was subtotal in 16 cases and confined to a generous biopsy in one. There was no operative mortality, but 2 deaths occurred in the early postoperative period. At discharge, neurological status was unchanged or improved in 35 cases. At 3-month follow-up examination, 12 patients were improved, 27 were unchanged and 3 were worsened. By January 1990 (6 to 72 months postoperatively) 27 of the first 40 patients treated were alive: 13 had resumed normal life, 6 were self-sufficient and 8 were disabled. The authors conclude that present-day microsurgical resection of intra-axial brainstem tumours is associated with low mortality and morbidity and affords favourable results for which they credit high-quality NMR imaging, efficient microsurgery, adequate anesthesia, and competent postoperative intensive care.

Updating a previous report, the authors offer a review of 45 patients between age 2 and 63 treated by direct surgical excision for brainstem tumours of various description. Since 1986 all candidate patients were examined by NMR imaging in addition to CT scanning, sometimes with the further addition of digital-subtraction vertebral angiography. By Epstein and McLeary’s criteria, 24 of the tumours were focal, 12 were cervicomedullary and 9 were diffuse. The most frequent histological diagnosis was glioma (36 cases between low-grade astrocytoma, anaplastic astrocytoma and glioblastoma); the balance was provided by cavernoma (6 cases), haemangioblastoma (2 cases), and lipoma (2 cases). Gross total resection was achieved in 28 patients, namely all those with ependymoma or vascular tumours and 14 of 17 with low-grade astrocytoma. Resection was subtotal in 16 cases and confined to a generous biopsy in one. There was no operative mortality, but 2 deaths occurred in the early postoperative period. At discharge, neurological status was unchanged or improved in 35 cases. At 3-month followup examination, 12 patients were improved, 27 were unchanged and 3 were worsened. By January 1990 (6 to 72 months postoperatively) 27 of the first 40 patients treated were alive: 13 had resumed normal life, 6 were self-sufficient and 8 were disable. The authors conclude that present-day microsurgical resection of intra-axial brainstem tumours is associated with low mortality and morbidity and affords favourable results-for which they credit high-quality NMR imaging, efficient microsurgery, adequate anesthesia, and competent postoperative intensive care.

This study reports the preliminary results obtained in a series of 107 patients with histologically proven malignant gliomas (86 glioblastomas and 21 anaplastic astrocytomas) operated upon between 1986 and 1989, with an aggressive attitude aimed to achieve extensive and possible "radical" excision of the tumor. Gross total removal was achieved in 62% of cases, while in the remaining the postoperative contrast enhanced CT scan showed more than 10-15% of residual tumor mass. There was no operative and postoperative mortality. The one-year survival rate was 60% in patients with total removal and 24% in those with partial resection. Furthermore the Karnofsky rating at discharge was improved in the former group while was unchanged in the latter. Although preliminary, these data seem to confirm the primary positive role of radical surgery in the combined management of malignant gliomas.

1572 Background: The efficacy of temozolomide (TMZ) is strictly related to the possibility to reach and maintain high and prolonged cellular drug concentrations in the target tissue. Evidence exists demonstrating that the achievement of this goal and the subsequent activity of TMZ are categorically schedule dependent. Aim of the present randomized phase II study is to verify whether a treatment schedule with TMZ appropriately modified induces better response rates along with a decrease of mielotoxicity as compared to the conventional one. Methods: Twenty patients (5 F/15 M), median age of 53 years (range 35–74), median Karnofsky PS 90 (range 70–100), with GBM in progression after surgery and adjuvant RT have been treated as follows: Schedule A - TMZ for 5 days in a 28-day cycle, at the dose of 150 mg/m2/d at the first cycle and of 200 mg/m2/d thereafter, up to a total of 8 cycles. Schedule B - TMZ for 7 days alternating with 7 days of rest up to a total of 12 cycles: the starting dose of TMZ at the first cycle was 50 mg/m2/d with progressive serial dose escalations of 25 mg/m2/d in the subsequent ones until the achievement of the dose of 150 mg/m2/d at the 5th cycle, and then keeping this regimen until the 12th cycle. Results: They are summarized in the table : Severe thrombocytopenia and stomatitis have been observed only in patients treated with Schedule A. Conclusions: These preliminary results, which deserve to be confirmed in a larger sample size, indicate that the treatment with TMZ on alternate week basis is strongly interesting and promising. In spite of the modality and the small number of patients included in this study, which doesn’t allow a direct comparison between two different treatments, it should be noted that schedule B achieved a 2-year OS and PFS rate of 40% and 20% respectively, compared to 10% and 0% of schedule A. [Table: see text] No significant financial relationships to disclose.

A case of opsoclonus and palatal myoclonus following blunt head injury is described. The syndrome appeared 1 month after the injury and lasted unchanged until death. Postmortem examination showed the

Summary This study concerns 1600 post-traumatic acute comas, who underwent combined clinical and EEG examinations. The EEG has been recorded accurately bedside several times a day throughout the acute stage. The obtained EEG patterns, generally considered to be polimorphous and extremely variable, can be classified into five basic groups corresponding to progressive deterioration of the cerebral electrogenesis: borderline, changeable, sleeplike, monotonous and silent. Borderline, sleep-like and changeable patterns, even though they indicate a varying degree of impairment of cerebral electrogenesis, prove nevertheless that the brain is capable of elaborating physiological rhythms and of modifying its activity in a spontaneous or evoked manner. True slow monotonous activity indicates an extreme degree of cerebral impairment; flattening, up to EEG silence, indicates the onset of brain death. Focal slowing and/or flattening, which often lacks surgical significance, is not considered in this classification. Focal or genezalized irritative activity in the early stages, however, indicates a more severe condition. EEG has often proved to be an useful means supporting the diagnostic and prognostic value of clinical examination.

This is a review of 1,000 consecutive cases of severe head injury admitted to our Neurosurgical Department between January 1973 and August 1976, before the advent of CT scanning. All patients were comatose following head injury (GCS⩽8) and were treated homogeneously by the same neurosurgical team by a protocol that included immediate resuscitation on arrival, diagnosis of intracranial lesions by angiography, early surgery when needed, mechanical ventilation, steroids, and mannitol. Extracranial lesions, even if preponderant, were treated by various specialists in the Neurosurgical Department, which for all practical purposes operated as an Emergency Department. Admission criteria were very broad with no preadmission selection. The overall mortality for this series was 45%. A little less than half the patients made good recoveries or remained moderately disabled (47%); 6% were severely disabled, and 2% survived in a persistent vegetative state. More than two-thirds of the patients were brought to our Neurosurgical Department after a short stay at a general hospital; 72% were admitted within 6 hours of injury; 71% were traffic accident victims; and 34% had significant associated extracranial injuries. Carotid angiography was performed in 78% of the patients and indicated the presence of an intracranial haematoma requiring surgery in 36% of the whole series. Mortality was significantly higher in operated than in unoperated patients (56% versus 39%); those treated surgically, however, were older, in worse clinical condition, and showed a higher incidence of acute subdural haematomas associated with brain contusion. Carotid angiography proved very effective in revealing the presence of an expansive lesion but failed to reflect the severity of brain damage, since the group with “negative” angiograms showed a high mortality (52%). Patients with a lucid interval had a higher percentage of surgical lesions than those with immediate coma (58% versus 26%); but fully 42% of them did not require surgery, and 25% had negative angiograms. From the prognostic point of view the clinical data elicited after initial resuscitation were highly predictive of the outcome: some individual neurological signs, such as mydriasis, posturing and eye movements, were not inferior to the GCS score in that respect. Age also proved a strong predictor, since elderly patients are more likely to have severe subdural and parenchymal lesions and their clinical severity is accordingly greater. Our series amounts to a data bank of cases both contemporary to and in good agreement with that collected by Jennett and his associates in their 1977 multinational study; and it affords a useful reference in the assessment of epidemiological variations and alternative management in relation to outcome.

To obtain continuous information about the cerebral electrical activity in the early course of coma, an apparatus was designed which included a small fast computer capable of calculating the Fourier transform. The practical application of this system of CSA to 123 comatose patients in a neurosurgical intensive care unit overcame the technical difficulties connected both with the patient's and environmental conditions. The advantages of such a technique are mainly due to its capacity of synthetising EEG signals and to its clarity of presentation, which is easily grasped even by people not specifically trained in electroencephalography. Hours of EEG activity are compressed into a pictorial and synoptic representation that shows in real time the distribution and temporal behaviour of frequencies as well as the intensity of total electrical activity. The immediate detection of these parameters permits evaluation of any worsening or improvement of cerebral electrogenesis, as well as of the inter-hemispheric asymmetries at their onset. EEG monitoring thus provides useful elements for assessing the comatose state in individual cases and for adjusting treatment. Finally, the spectrographic aspect of the first 48 h, as a whole, carries a great prognostic significance. The most striking finding from this study was the confirmation that the comatose states that, in their early course, show only a fixed slow-wave EEG activity are far more rare than those that display an electrical activity changing in time.

This is a study of the changes that have occurred in the field of severe head injury since the advent of CT scanning, comparing two homogeneous series of patients selected by clinical status (Glasgow Coma Scale less than or equal to 8), namely a series of 1,000 cases admitted to our Department between 1973 and 1976, already published in this Journal, and one of 385 cases cared for between 1979 and 1980, when CT scanning had become generally available. The two series of patients compare very closely in many respects, particularly in the incidence of surgical cases. In the more recent series the overall outcome was better both in surgical and in non-surgical cases. Among patients in the CT scan series the incidence of brain contusion associated with haematoma was greater than that of pure subdural haematomas. In non-surgical patients the CT scan, unlike cerebral angiography, afforded better identification of traumatic lesions and the grouping of patients into homogeneous categories correlating with a given outcome. On admission, cerebral angiography and CT scanning were equally effective in detecting lesions of surgical import; later in the course of the illness, however, CT scanning proved far more effective in detecting changes, with fully 15% of the patients being referred for surgery in the light of repeat CT scan findings as opposed to only 4% undergoing surgery on the indications of repeat angiography. Also, in the new series the mean interval from injury to surgery was shorter, with 64% of patients being operated on within 6 hours of the injury.(ABSTRACT TRUNCATED AT 250 WORDS)

A case of opsoclonus and palatal myoclonus following blunt head injury is described. The syndrome appeared 1 month after the injury and lasted unchanged until death. Postmortem examination showed the presence of widespread lesions of the brain stem affecting the dentato-rubro-olivary system. The main clinical features of the syndrome and their anatomical correlates are discussed.

Patients in the early stage of severe head injuries occasionally present with a clinical picture analogous to that in vascular or neoplastic pontine lesions and they can be identified by careful clinical examination and by repeated electroencephalography (E.E.G.). The commonest features in these cases were preservation of consciousness, constriction of the pupils, disturbances of reflex ocular motility, severe pyramidal deficits, decerebrate rigidity, myoclonic manifestations, irregular breathing, and cranial nerve palsies. An E.E.G. tracing similar to the normal pattern was a common finding. These observations suggest that pontine syndromes may be directly produced by blunt head injuries. These findings also give a warning of the possibility of mistaking a non-reacting, but conscious, patient for one who is deeply comatose.

In the acute stage of head injury, careful clinical examination gives the most reliable assessment of severity of the brain damage and it can detect any changes in conscious level, providing indications both for the practical management and for the ultimate outcome.

✓ Prolonged coma following severe head injury is a serious condition because it implies a poor prognosis. In order to assess the magnitude of this phenomenon, the authors have reviewed 135 cases of posttraumatic unconsciousness lasting more than 2 weeks, from among the entire propulation of patients with severe head injury managed in 10 years in their neurosurgical intensive care unit. The incidence of prolonged coma was 4% of all patients with acute traumatic coma, and 0.6% of all hospitalized patients with head injury. By 1 year after trauma, 30% of the patients had died, 8% survived in a vegetative state, 31% survived with severe disabilities, and 31% had made a satisfactory recovery. The early clinical picture of prolonged unconsciousness has no predictive value as to further evolution. Patients emerge from unconsciousness in consecutive steps representing the restoration of increasingly complex neurological functions; the timing of these steps is very variable and sometimes covers several months. The time distribution of recovery steps in individual cases is of limited predictive value as to outcome. The most frequent state during the recovery process is the condition of wakefulness without awareness, which should not be pronounced “permanent” earlier than 1 year after injury.

✓ A comprehensive study of the motor patterns, usually grouped under the heading “decerebrate rigidity,” was carried out in a series of 800 patients with severe head injuries. The incidence of these manifestations was 39.6%, and when they were present chances of survival were reduced from 79.4% to 28.1%. Clinical and electromyographic investigations revealed heterogeneous and unstable motor manifestations that did not fit into the classical groups of experimental models of decerebrate rigidity. Combinations of extensor and flexor attitudes and/or responses were frequently found in the same patient, but could be separated into homogeneous groups. Each recognized postural pattern had its own distinct neurological signs and prognosis. Age did not significantly affect the outcome; however, intracranial expanding lesions (73.5%), impairment of the brain-stem oculomotor system (49.8%), and deep coma (88.9%) all contributed to an unfavorable course. Surgical treatment was effective when performed for intracranial hematomas and in patients with incomplete extensor rigidity. Good recovery was achieved in 16% of decerebrate patients, while 12.1% survived in prolonged coma or with severe disabilities. All clinical and neuropathological data suggest that extensor motor abnormalities in the acute phase of cerebral traumatic disease do not always conclusively indicate structural brain-stem damage. A critical analysis of so-called “decerebrate rigidity” (rejecting in some instances its Sherringtonian implications) may allow for a more accurate clinical assessment of the severity of head injury.

This study concerns 1600 post-traumatic acute comas, who underwent combined clinical and EEG examinations. The EEG has been recorded accurately bedside several times a day throughout the acute stage. The obtained EEG patterns, generally considered to be polimorphous and extremely variable, can be classified into five basic groups corresponding to progressive deterioration of the cerebral electrogenesis: borderline, changeable, sleep-like, monotonous and silent. Borderline, sleep-like and changeable patterns, even though they indicate a varying degree of impairment of cerebral electrogenesis, prove nevertheless that the brain is capable of elaborating physiological rhythms and of modifying its activity in a spontaneous or evoked manner. True slow monotonous activity indicates an extreme degree of cerebral impairment; flattening, up to EEG silence, indicates the onset of brain death. Focal slowing and/or flattening, which often lacks surgical significance, is not considered in this classification. Focal or generalized irritative activity in the early stages, however, indicates a more severe condition. EEG has often proved to be an useful means supporting the diagnostic and prognostic value of clinical examination.

Spontaneous electrical activity (EEG) and event-related computer averaged brain electrical potentials (EPs) are becoming an integral part of CNS function monitoring in neurological intensive care patients. EEG monitoring using the compressed spectral array (CSA) computer analysis offers continuous information about cerebral electrical activity, permitting an accurate definition of the severity of brain injury, forecasting patient's course, and early detection of secondary intracranial changes. It offers more precise indications for treatment and prognosis. Combining EEG with multimodality EPs permits a finer diagnosis of the location and extent of CNS damage and contributes information, not otherwise obtainable, on the integrity of CNS pathways. Changes is electrophysiological patterns are often related to changes in other physiological parameters or events affecting the patient. Consequently, it appears advantageous to monitor simultaneously other CNS and body functions and record, process and display the data obtained in the patient care area. To make this comprehensive monitoring system reliable and useful, a wise application of advanced computer technology and a high degree of understanding of intracranial dynamics are required.

Doppel (PRND) is a paralogue of the mammalian prion (PRNP) gene. It is abundant in testis and, unlike PRNP, it is expressed at low levels in the adult central nervous system (CNS). Besides, doppel overexpression correlates with some prion-disease pathological features, such as ataxia and death of cerebellar neurons. Recently, ectopic expression of doppel was found in two different tumor types, specifically in glial and haematological cancers. In order to address clinical important issues, PRND mRNA expression was investigated in a panel of 111 astrocytoma tissue samples, histologically classified according to the World Health Organization (WHO) criteria (6 grade I pilocytic astrocytomas, 15 grade II low-grade astrocytomas, 26 grade III anaplastic astrocytomas and 64 grade IV glioblastoma multiforme). Real-time PRND gene expression profiling, after normalisation with GAPDH, revealed large differences between low (WHO I and II) and high grade (III and IV) of malignancy (P