A diagnostic flowchart, including TCD, Xe-CT and angiography, to improve the diagnosis of vasospasm critically affecting cerebral blood flow in patients with subarachnoid haemorrhage, sedated and ventilated.

The aim of this study was to prospectively evaluate a clinical protocol including transcranial doppler (TCD), Xenon-CT (Xe-CT) and angiography, for the detection of vasospasm leading to critical reductions of regional cerebral blood flow (rCBF) in both ventilated and sedated SAH patients, i.e. patients in whom clinical evaluation was not possible. Seventy-six patients were prospectively included in a surveillance protocol for daily TCD vasospasm monitoring. When TCD showed a V(mean) above 120 cm/sec in the middle cerebral artery (MCA), patients underwent Xe-CT study. If rCBF in the MCA was reduced to below 20 ml/100 g/min or if there was a reduction in the rCBF with significant asymmetry between the two MCAs, angiography was performed. Conversely, further Xe-CT and angiography were not obtained unless the TCD V(mean) values reached values above 160 cm/sec. In 35 patients, V(mean) attained values above 120 cm/sec, but only in five of them, rCBF was suggestive of vasospasm, and angiography confirmed the diagnosis in four. The protocol suggests that in sedated and ventilated patients, detection of a critical rCBF reduction due to vasospasm is possible to allow for more specific treatment and to reduce undue medical complications.

Two-stage treatment of a tectal ganglioglioma: endoscopic third ventriculostomy followed by surgical resection.

Tumours of the quadrigeminal plate in adults are usually benign. Nevertheless, obstructive hydrocephalus due to compression of the Sylvian aqueduct is an almost invariable early finding. Whether or not direct excision is undertaken, temporary or permanent treatment of the hydrocephalus is warranted. Endoscopic third ventriculostomy is an alternative to insertion of a shunt and provides both acute and long-term relief of hydrocephalus-related symptoms. We chose a two-stage approach for treating a tectal ganglioglioma in an adult: endoscopic third ventriculostomy followed by surgical excision. The advantages and disadvantages of each therapeutic strategy are discussed.

Regional cerebral blood flow levels as measured by xenon-CT in vascular territorial low-density areas after subarachnoid hemorrhage are not always ischemic.

INTRODUCTION: The aim of this study was to assess regional cerebral blood flow (rCBV) in areas of CT hypoattenuation appearing in the postoperative period in patients treated for aneurysmal subarachnoid hemorrhage (SAH) using xenon-enhanced CT scanning (Xe-CT). METHODS: We analyzed 15 patients (5 male and 10 female; mean age 49.7+/-12.1 years) with SAH on CT performed on admission to hospital and who showed a low-density area within a well-defined vascular territory on CT scans after clipping or coiling of a saccular aneurysm. All zones of hypoattenuation were larger than 1 cm(2) and showed signs of a mass effect suggesting a subacute phase of evolution. Two aneurysms were detected in two patients. Aneurysms were located in the middle cerebral artery (n=7), in the anterior communicating artery (n=6), in the internal carotid artery (n=3), and in the posterior communicating artery (n=1). Treatments were surgical (n=8), endovascular (n=2) or both (n=1). A total of 36 Xe-CT studies were performed and rCBF values were measured in two different regions of interest (ROI): the low-density area, and an area of normal-appearing brain tissue located symmetrically in the contralateral hemisphere. RESULTS: rCBF levels were significantly lower in the low-density area than in the contralateral normal-appearing area (P<0.01). In the low-density areas, irreversible ischemia (CBF <10 ml/100 g per minute) was present in 11/36 lesions (30.6%), ischemic penumbra (CBF 10-20 ml/100 g per minute) and oligemia (CBF 20-34 ml/100 g per minute) in 8/36 lesions (22.2%), relative hyperemia (CBF 34-55 ml/100 g per minute) in 7/36 lesions (19.4%), and absolute hyperemia (CBF >55 ml/100 g per minute) in 2/36 lesions (5.6%). CONCLUSION: Our study confirmed that rCBF is reduced in new low-density lesions related to specific vascular territories. However, only about one-third of the lesions showed rCBF levels consistent with irreversible ischemia and in a relatively high proportion of lesions, rCBF levels indicated penumbral, oligemic and hyperemic areas.

Central neurocytoma of the fourth ventricle. Case history.

Central neurocytomas are low-grade tumours of neuronal origin, affecting mainly young patients and usually located in the lateral or third ventricle. We report a rare case of central neurocytoma at the fourth ventricle level. Magnetic resonance imaging showed a homogeneously enhancing mass lesion at the fourth ventricle. Gross-total surgical removal was achieved. The histological diagnosis was of central neurocytoma but the lesion showed a fairly elevated Ki-67 index (6%). Given this finding, close neuroimaging monitoring was performed and at the moment the patient is free of recurrence.

Cerebral blood flow in mean cerebral artery low density areas is not always ischemic in patients with aneurysmal subarachnoid hemorrhage--relationship with neurological outcome.

Aneurysmal subarachnoid hemorrhage (SAH) can be complicated by reduction of regional cerebral blood flow (rCBF) from large conductance vessels leading to focal edema appearing as an area of hypoattenuation on CT. In this study we included 29 patients with SAH due to aneurysmal rupture, having 36 CT low density areas within the middle cerebral artery territory in whom a total of 56 Xenon-CT (Xe-CT) studies were performed. Collectively, we evaluated 70 hypoattenuated areas. rCBF levels were measured in two different regions of interest drawn manually on the CT scan, one in the low density area and the other in a corresponding contralateral area of normal-appearing brain tissue. In the low density area (22.6 +/- 22.7 ml/100 gr/min) rCBF levels were significantly lower than in the contralateral area (32.8 +/- 17.1 7 ml/100 gr/min) (p = 0.0007). In the injured areas deep ischemia (CBF < 6 ml/ 100 g/min) was present in only 25.7% of Xe-CT studies, suggesting that hypodense areas are not always ischemic, whereas in 43.7% of the lesions/Xe-CT studies we found hyperemic values. Patients with a better outcome had hyperemic lesions, suggesting brain tissue recovery in injured areas.

Loco-regional radioimmunotherapy of high-grade malignant gliomas using specific monoclonal antibodies labeled with 90Y: a phase I study.

A Phase I radioimmunotherapy trial was conducted in which radioconjugated monoclonal antibody (MAb) was directly infused into the tumor or postoperative tumoral bed in patients with high-grade malignant glioma. BC-4, a murine MAb that recognizes tenascin, was used in these studies. The MAb was labeled with 90Y, a pure beta emitter with maximum energy of 2.284 MeV, which can penetrate into tissue up to 0.5-0.7 cm. Stable 90Y-labeled MAb conjugates were prepared using the chelator p-isothiocyanatobenzyl derivative of diethylenetriaminepentaacetic acid (ITC-Bz-DTPA), obtaining >95% labeling efficiency and conserving the antibodies' immunoreactivity (>85%). Twenty patients, 2 with anaplastic astrocytoma and 18 with glioblastoma, were included in the study. All of the patients had been treated previously with conventional therapies (surgery, external radiotherapy, and chemotherapy) and presented with progressive disease not amenable to further treatment. A dose-escalation study was performed using doses ranging from 5-30 mCi (185-1110 MBq) of 90Y-labeled MAb BC-4. The protein dose of MAb was always 1 mg. Three patients were treated at the 5, 10, 15, and 20 mCi levels, and the 25- and 30-mCi doses were each administered to 4 patients. Systemic toxicity was completely absent in all of the patients. The maximum tolerated dose to the brain was 25 mCi (925 MBq). The average dose to the tumor was 3200 cGy/mCi. Doses to the liver, bone marrow, and kidneys were below 10 cGy/mCi in all of the cases. Biodistribution studies demonstrated that the 90Y-labeled MAb accreted exclusively in the neoplastic area without any diffusion into the normal brain or other normal organs. No clinical responses were recorded because of the very advanced stage of disease at the time of radioimmunotherapy.

131I radioconjugated antibodies for the locoregional radioimmunotherapy of high-grade malignant glioma--phase I and II study.

Locoregional radioimmunotherapy (LR-RIT) was administered to 111 patients (20 were recruited in a phase I and 91 in a phase II study) with malignant gliomas: 1 patient with oligodendroglioma, 7 patients with anaplastic oligodendroglioma, 2 with grade II astrocytoma, 10 with anaplastic astrocytoma and 91 with glioblastoma, amounting to 58 newly diagnosed and 53 recurrent tumours. The 131I-labelled monoclonal antibodies BC-2 and BC-4 were used in order to recognize stromal and intracellular glycoprotein tenascin, an antigen present particularly in glioblastoma. The patients were enrolled between February 1990 and December 1997 after conventional therapy. The radiopharmaceutical was injected directly into the tumour site. Sequential scintigraphies demonstrated a high and enduring uptake in the tumour. The mean irradiation dose in the tumour was 300 Gy per cycle. In the group of 74 phase II glioblastoma patients the clinical responses were as follows: 10 patients with stable disease (SD), 9 with partial responses (PR), 23 with no evidence of disease (NED) and 1 patient with complete response (CR). The median survival was 19 months. The response rate (CR + PR + NED) was 17.8% for those patients with bulky lesions, with a median survival of 17 months, but 66.6% for patients with small lesions, with a median survival of 25 months. Better outcomes were recorded in cases with less aggressive diseases: oligodendroglioma, anaplastic oligodendroglioma and anaplastic astrocytoma. We conclude that fractionated LR-RIT can be safely performed, with promising results especially in patients with minimal disease.

Local application of radiolabeled monoclonal antibodies in the treatment of high grade malignant gliomas: a six-year clinical experience.

BACKGROUND: Infusion of radiolabeled monoclonal antibodies (MAbs) directly into a tumor or into the site of disease after surgery concentrates a high quantity of antibody and radioisotope in the neoplastic tissue. The strong irradiation delivered by this method can result in control of high grade malignant gliomas. METHODS: Antitenascin MAbs BC-2 and BC-4 labeled with 131I (mean dose, 1998 MBq) were injected into 105 patients with malignant glioma by means of an in-dwelling catheter. Multiple courses (up to six) were given. The patients underwent MAb treatment after their tumors were minimized by surgery, radiotherapy, and, in recurrent lesions, a second operation. Data is presented in this article for 62 evaluable patients with high grade malignant gliomas (58 glioblastomas and 4 anaplastic astrocytomas), of which 31 were newly diagnosed tumors and 31 were recurrent lesions. In 40 cases the disease was minimal at the time of MAb injection, and in 22 cases a macroscopic remnant was present. RESULTS: There were very few adverse effects, all of which were minor. The treatment yielded a significant extension of patients' median survival (23 months) and of the disease free time to relapse (12 months). Favorable objective responses were recorded as follows: 9 partial responses, 3 complete responses, and 20 with no evidence of disease. A response rate of 51.6% was calculated for all assessable patients. The most important factor in obtaining beneficial outcomes was limited extension of the neoplasm at the time of therapy. CONCLUSIONS: In selected patients, locoregional radioimmunotherapy can be included in a multimodal strategy to control high grade malignant gliomas and produce favorable results.

Local treatment of malignant gliomas by direct infusion of specific monoclonal antibodies labeled with 131I: comparison of the results obtained in recurrent and newly diagnosed tumors.

Two murine monoclonal antibodies, BC-2 and BC-4, raised against tenascin and labeled with 131I were infused locally in the site of neoplastic disease by means of a removable (16 patients) or indwelling (34 patients) catheter. Fifty patients bearing a malignant glioma were treated. Twenty-six of these were suffering from recurrent disease; their tumors relapsed within 9 months (median) after treatment. The remaining 24 cases had a newly diagnosed tumor, and local radioimmunotherapy (RIT) was given immediately after surgery and radiochemotherapy. All efforts were made to reduce the tumor before the infusion of the radiopharmaceutical. Therefore, 22 cases with relapsing glioma underwent additional debulking surgery, which led to total or subtotal removal of tumor in 9 of the patients. Altogether, 28 patients had intralesional RIT when the disease was minimal or microscopic. Conversely, 22 cases underwent local RIT with a tumor the diameter of which was > 2 cm. In many cases, the infusions were repeated up to six times to achieve complete destruction of the neoplastic tissue. The local treatment did not give rise to systemic or to cerebral adverse effects. The labeled monoclonal antibodies, given directly in the site of the lesion, concentrated in very high amount in the neoplastic tissue and remained fixed in the target for a long period of time. For these reasons, the radiation dose to the tumor was remarkable (on average > 30,000 cGy/cycle) and consequently led to promising results. The median survival was, in total, 20 months (18 in recurrent tumors and 23 in newly diagnosed lesions). Moreover, median survival was 17 months in patients with bulky tumors (both recurrent and newly diagnosed tumors) and 26 months in patients with minimal or microscopic disease. The median time to progression was 3 months in recurrent and 7 months in newly diagnosed gliomas. Finally, RIT produced 3 CRs (all in recurrent tumors), 6 PRs (4 in recurrent and 2 in newly diagnosed), and 11 stabilizations of disease (4 in recurrent and 7 in newly diagnosed). In 19 cases (13 recurrent and 6 newly diagnosed) the progression of tumor was recorded. Eleven patients (2 recurrent and 9 newly diagnosed) who were treated by RIT when their disease was minimal and nondetectable by radiological methods remained disease-free and were classified as NED. The overall response rate (NED plus CR plus PR) was 40% (34.6% recurrent and 45.8% newly diagnosed).(ABSTRACT TRUNCATED AT 400 WORDS)

Intralesional administration of I-131 labelled monoclonal antibodies in the treatment of malignant gliomas.

The authors report their preliminary experience with the use of radiolabelled monoclonal antibodies (MAb) as an adjuvant treatment for 33 malignant gliomas. MAbs employed in this study are raised against Tenascin (TN) which is an antigen of the extracellular matrix of the tumour. It has also been found in neoplastic cells but never in normal brain tissue. This therapy is aimed to give a local high dose radiation (boost) while sparing healthy brain structures. This treatment has always been well tolerated and no adverse reactions at the level of CNS or major extraneural organs has been observed. Significant improvement of median survival has been obtained but this result should be cautiously evaluate since the study is non-randomized. Comparison with other current adjuvant technique is briefly discussed.

Intralesional radioimmunotherapy of malignant gliomas. An effective treatment in recurrent tumors.

BACKGROUND: Intralesional radioimmunotherapy (RAIT) may improve the management of malignant gliomas whose prognosis is, at present, very poor. Current treatment modalities (e.g., surgery, radiotherapy, and chemotherapy) may prolong survival by a few months but cannot prevent tumor recurrence. METHODS: Following one or more surgical operations, radiotherapy, and chemotherapy, 24 patients with recurrent malignant gliomas (23 brain and 1 spinal cord) underwent RAIT with 2 murine monoclonal antibodies (MoAb), BC-2 and BC-4, raised against tenascin (TN). This antigen is expressed in large amounts in the stroma of glial tumors but not normal brain tissue. The isotope used was iodine-131 (131I). The radiolabelled antibodies were injected directly into the tumor by means of a removable catheter or an indwelling catheter placed in the site of disease at the time of craniotomy. The patients were admitted to the protocol if histochemical analysis of their tumors demonstrated the presence of TN in high abundance. Biodistribution and dosimetry of an intralesional tracer dose (1 mg MoAb and 37 MBq 131I) were studied. RAIT was performed by the administration of escalating doses of radioiodine, ranging from 15 mCi to 57 mCi. In many cases, RAIT was was repeated two, three, or four times (on 8, 3 and 4 patients, respectively). RESULTS: Pharmacokinetic data resulted, on average, as follows: the 24-hour tumor/background ratio was 16.6; the percentage of injected dose concentrated per gram of tumor at 24 hours was 2.4%; and the effective half-life of the MoAb at the tumor was 74.5 hours. The mean radiation dose to the tumor was 36.48 cGy per MBq of 131I injected. Both systemic and brain toxicities were absent, while human anti-mouse antibody production after MoAb administration occurred in only a few cases. At present, 17 patients are assessable, with a median survival time of 16 months. Objective responses consisted of 5 tumor stabilizations (median time, 9 months), 3 partial remissions (11 months), and 3 complete remissions (15 months).

MRI of an unenhancing tuberculum sellae meningioma.

We present a tuberculum sellae meningioma with intrasellar extension which did not enhance with intravenous gadolinium. Identification of the diaphragma sellae, possible only on the unenhanced short TR/TE sequence, was crucial for differentiating the lesion from a pituitary adenoma, and therefore for the correct surgical approach.

Arachnoid cyst of middle cranial fossa and ipsilateral subdural haematoma: diagnostic and therapeutic implications in three cases.

We describe three cases of arachnoid cyst of the middle cranial fossa with associated intracystic and subdural haematomas. In all of the patients the diagnosis was made before surgical treatment. No bleeding could be attributed to ruptured bridging veins. In two cases the source of bleeding was identified at the interface between the dura mater and the outer membrane at the temporal skull base. We suggest that, even if wide outer membrane membranectomy is probably not indicated, careful coagulation of the membrane at the skull base is necessary to avoid bleeding within the cyst.

Acute bilateral extradural haematomas in an adult.

A case of acute bilateral extradural haematomas in an adult head-injured patient is presented. The literature concerning such an extremely rare condition is reviewed.

[Activation with amitriptyline: electroclinical comments on 120 epileptic patients (author transl's)]. / Activation par l'amitriptyline (Remarques électrocliniques à propos de 120 patients épileptiques).

The sleep-inducing and epileptogenic effects of amitripyline (0.5 mg/kg i.m.) were studied in 120 epileptic patients. Sleep occurred in 94 p. 100 of the patients: 92 p. 100 showed stages I and II, 42 p. 100 also showed stages III and IV, but only 12 p. 100 showed REM. Major activation of inter-ictal abnormalities occurred in 41 p. 100 and seizures were provoked in 17 patients (14 p. 100). Neutral results were obtained in 23 p. 100 of cases. The results obtained and the complete absence of drawbacks recommend amitriptyline for use in studying epileptic patients, at least before turning to other pharmacological techniques which are more dangerous and probably less reliable.