Wegener's granulomatosis confined to nervous system.

Wegener's granulomatosis (WG) is a multisystemic necrotising granulomatous vasculitis of small and medium sized vessels, that primarily involves the upper and lower respiratory tracts, lung tissues and kidneys. Serum antineutrophil cytoplasmic antibodies (ANCA) are a sensitive and specific marker of WG. Whereas the peripheral nervous system is often involved in WG, central nervous system manifestations are reported only in 2-8%, and are rarely present at onset. We report on a patient with atypical neurological presentation of ANCA negative WG in whom the diagnosis was made only after a meningeal biopsy.

Predictive value of ANCA in atypical primary brain localization of Wegener's granulomatosis.

Wegener's Granulomatosis is a necrotizing vasculitis generally involving upper and lower respiratory tract and kidneys. The central nervous system is involved in less than 10% of the patients during the course of the disease and primary involvement is even rarer. We present and discuss the case of a patient with primitive cerebral localization of Wegener's Granulomatosis in which the diagnosis and the beginning of correct therapy were delayed, in spite of a rising c-ANCA titer, due to a misinterpretation of a bioptic specimen. This delay caused renal damage and pulmonary cavitations which needed a long time to recover. This case report suggests that the central nervous system can be the site of a primary localization of Wegener's Granulomatosis even without any other organ involvement. The diagnosis must be made as soon as possible in order to prevent spread to other sites since the disease is usually very aggressive and severe.

Temozolomide as a second-line systemic regimen in recurrent high-grade glioma: a phase II study.

BACKGROUND: To investigate the efficacy of temozolomide in relation to response rate, toxicity, time to progression. and median survival time, a phase II study was conducted in patients with recurrent high-grade glioma following surgery plus radiotherapy and first-line chemotherapy based on nitrosourea, procarbazine and vincristine. PATIENTS AND METHODS: Forty-one patients with high-grade glioma, at second recurrence or progression, of which twenty-two (54%) had glioblastoma multiforme, ten (24%) anaplastic astrocytoma, and nine (22%) anaplastic oligodendroglioma were administered temozolomide, 150 mg/m2/daily for five days every four weeks. RESULTS: Response was assessed in 40 patients. The overall response rate (complete + partial response) was 22.5% (95% confidence interval (CI): 9.5%-35%). The median time to progression for all 41 patients was 22.3 weeks; progression-free survival at 6 and 12 months was 48.5% and 34.7%, respectively. Median survival time was 37.1 weeks with 80.2% at 6 and 34.9% survival at 12 months. CONCLUSIONS: On multivariate analysis, response to previous treatment was significant (P = 0.03) for time to progression and Karnofsky performance score for overall survivall (P = 0.002). Temozolomide gave a moderate response rate with acceptable toxicity as second-line chemotherapy in patients with recurrent high-grade glioma.

Procarbazine and high-dose tamoxifen as a second-line regimen in recurrent high-grade gliomas: a phase II study.

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.

Cerebral aspergillosis in a liver transplant recipient: a case report of long-term survival after combined treatment with liposomal amphotericin B and surgery.

Cerebral aspergillosis is a life-threatening complication in liver transplant recipients, with mortality rates approaching 100%; treatment with amphotericin B is of limited efficacy because of its poor distribution in the cerebrospinal fluid and its systemic side effects. We report the case of a liver transplant recipient who developed recurrent cerebral Aspergillus fumigatus infection, and was successfully treated by combined surgical excision of the lesion and administration of liposomal amphotericin B. This first report of long-term complication-free survival in a liver transplant recipient suggests that therapy with liposomal amphotericin B may reduce the risk of recurrence of cerebral aspergillosis in these immunocompromised patients.

Phase II trial with BCNU plus alpha-interferon in patients with recurrent high-grade gliomas.

A Phase II study with a combination of BCNU and alpha-interferon (IFN) was conducted in patients with high-grade glioma recurrent after surgery and radiation treatment in order to investigate tumor control and toxicity. Twenty-one non-chemotherapy pretreated patients were administered 6 MU alpha-IFN in a 2-h infusion followed by 150 mg/m2 BCNU i.v. on day 1. Three MU alpha-IFN were subsequently administered subcutaneously on alternating days three times a week, until recycling of the whole procedure on day 42. Among 21 patients, partial remission was obtained in 7 (33%; 95% CI = 15-57) and stable disease in 6 (29%; CI = 11-52); overall Kaplan-Meier median time to progression (TTP) was 4.5 months (CI = 4-9) and the overall median survival time (MST) was 7 months (CI = 5-13). In patients who underwent surgical redebulking prior to chemotherapy, TTP and MST were 9 (CI = 7-14) and 15 months (CI = 11.0-39.0); in patients who were not operated on again before chemotherapy, these values were 4 (CI = 2-5; log rank test, p = 0.0026) and 5.5 months (CI = 4-7; log rank test, p = 0.0012) respectively. The results of this regimen in relapsing patients, especially following surgical redebulking, are encouraging; toxicity is acceptable, and further studies on combined alpha-IFN and multiple-agent chemotherapy are warranted.

Early chemotherapy and concurrent radio-chemotherapy in high grade glioma.

PURPOSE: The poor results from treatment of high grade glioma prompted us to explore new protocols involving concurrent radio-chemotherapy. Our primary objective was to evaluate the feasibility of very early postoperative chemotherapy with BCNU, concurrent radio-chemotherapy with carboplatin and teniposide, and post-radiotherapy BCNU. Our secondary objectives were to evaluate time to progression, and overall survival. PATIENTS AND METHODS: We treated 24 newly diagnosed patients (pts) with BCNU 150 mg/m2 seven days after surgery. Thirty days later, we started radiotherapy, 1.8 to 2 Gy/day for 5 days a week on limited fields up to 60 Gy, and concurrent chemotherapy with carboplatin 250 mg/m2 on days 1, 22, and 43, and teniposide 50 mg/m2 on days 1, 2, 3, 22, 23, 24, 43, 44 and 45. Two cycles of 150 mg/m2 BCNU were then given at 30 and 70 days, respectively, after the end of the radio-chemotherapy course. Therapy was then suspended, but if disease progression was evident, treatment was resumed with drugs that had not been previously employed. Surgical reintervention was not routinely considered. RESULTS: Following radio-chemotherapy treatment in the 24 pts evaluable for response, we observed partial remissions in 8 cases (33%) and stable disease in 12 (50%). Actuarial estimates of progression free survival (PFS) were 33 weeks, with 56 wks for anaplastic astrocytoma and 31 weeks for glioblastoma. Median survival time (MST) of all pts was 58 weeks; 51 weeks for glioblastoma and was not reached for anaplastic astrocytoma. This regimen was feasible. Of 144 planned cycles, 139 were delivered, and among these only in 13 and 9 cycles the doses were reduced by 75 and 50%, respectively. We did not observe any gastrointestinal toxicity. Grade 2 hematological toxicity occurred in 25% of pts. grade 3 in 4% and neurological toxicity in 3% of the pts during BCNU delivery, probably due to a sharp increase in intracranial pressure. CONCLUSION: Early chemotherapy, concurrent chemo-radiotherapy and brief post-radio-therapy chemotherapy are feasible and well tolerated. The objective response and disease stabilization rates appear similar to previous experiences.

Primary intrasellar coccidioidomycosis simulating a pituitary adenoma.

The case of a 68-year-old woman who had relatively acute, unilateral ophthalmoplegia is reported. Radiological studies indicated a mass lesion involving the pituitary gland and left cavernous sinus. Pathological tissue obtained by the transsphenoidal approach revealed the presence of a Coccidioides granuloma. This pathological entity should be considered when evaluating patients with a pituitary mass and ophthalmoplegia.

Giant-cell granulomatous hypophysitis: a distinct clinicopathological entity.

Idiopathic giant-cell granulomatous hypophysitis is a chronic inflammatory disorder of the pituitary gland. It presents clinically as a sellar mass lesion with pituitary insufficiency and/or hyperprolactinemia, and is radiologically indistinguishable from a pituitary tumor. In most of the previously reported cases the documentation of the disorder has been limited to autopsy tissue. Only a few cases documented by biopsy have been recorded. Four cases are presented here with radiological, endocrinological, and surgical findings. The appropriately documented cases collected from the literature and the present series are reviewed and the incidence, patterns of clinical and radiological presentation, and operative management of this disorder are discussed. This entity should be considered when evaluating patients with a pituitary mass and evidence of hypopituitarism and hyperprolactinemia.

Intracerebral hematoma following evacuation of chronic subdural hematomas. Report of two cases.

Two cases of intracerebral hemorrhage occurring after evacuation of bilateral chronic subdural hematomas are reported. Possible pathogenic mechanisms included hemorrhage into previously undetected areas of contusion, damage to cerebral vasculature secondary to rapid perioperative parenchymal shift, and sudden increase in cerebral blood flow combined with focal disruption of autoregulation; of these, the latter mechanism seemed most likely to be responsible for the hematoma formation. The need for clinical awareness of this nearly uniformly devastating complication, as well as prompt use of computerized tomography scanning in assessing the postoperative course, are stressed.

Disendocrine manifestations during non tumoral aqueductal stenosis.

Disendocrine manifestations during aqueductal stenosis are more and more frequently reported in literature. In the present study, 20 cases of benign aqueductal stenosis associated with disendocrine features as amenorrhea, obesity, polydipsia and polyuria, dwarfism, acromegalic features, hypogonadism, precocious puberty, gigantism are stressed. Authors discuss clinical findings and pathogenetic hypothesis on the base of endocrine, neurological and peculiar radiological features with the support of a wide literature review.

Aqueductal stenosis following mumps virus infection. Case report.

A case of aqueductal stenosis following mumps infection is reported, to the authors' knowledge the 12th case in the literature. The pathogenetic events are discussed and the literature reviewed.

Long-term immunological investigation of malignant intracranial gliomas.

In this study, 118 consecutive adult patients with supratentorial gliomas underwent preoperative immunological monitoring, with particular regard to B-lymphocyte and T-lymphocyte markers. Most patients were treated surgically and with radiotherapy. Three months later, they were readmitted for postoperative immunological investigation and follow-up control. A total of 76 cases could thus be completely investigated and were statistically eligible for evaluation. A pronounced failure of T-cell-mediated immunity was observed: "E-active" rosette-forming cells and mitogen-induced blastogenesis tests turned out to be markedly depressed, with a slight postoperative recovery. Spontaneous cell-mediated cytotoxicity was significantly (p less than 0.01) increased both in preoperative and postoperative findings. The main immunodiagnostic patterns (immunoglobulins assay, surface immunoglobulins, "mouse" rosettes) concerning the B-cell-dependent "pool" were found to be within normal limits.

Further studies on clotting changes in patients with cerebral sinus thrombosis. A case with thrombosis of right transverse sinus.

A 28 year old woman with angiographically proven thrombosis of right cerebral transverse sinus was studied from a clotting point of view. The changes noted were decreased fibrinolytic activity and increased collagen platelet aggregation. The patient presented loss of consciousness, aphasia, mental confusion, migh right hemiparesis, papilloedema. The treatment with dipyridamole, aspirin and a nicotinic acid derivative was followed by good results. After about a month the fundus reverted to normal. A clotting study is indicative in every patient with cerebral venous thrombosis.

Clinical and experimental immunobiology of medulloblastomas.

A wide pre- and postoperative immunological monitoring of B- and T-cell markers in children with medulloblastomas is presented. Preoperative investigations showed a noticeable failure of T-cell-dependent immunity, currently identified by "active" E-rosette forming cells (Ea-RFC) and blastogenesis tests, with a significant increase of spontaneous cell-mediated cytotoxicity (SCMC). In postoperative long-term controls, a slight recovery of Ea-RFC and blastogenesis tests was observed. The main findings concerning cytotoxicity kinetics are discussed.