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Aim: To describe our experience in treating vitreoretinal involvement of primary central nervous system lymphoma, by intravitreal injections of methotrexate (MTX). Methods: Patients with suspected intraocular lymphoma underwent a diagnostic vitrectomy. Samples were sent for cytology, genetic evaluation and for interleukin level measurements. Treatment protocol included injection of 400 μg/0.1 ml MTX intravitreally twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months, for a total of 25 injections. Data were collected from the patients’ records and included, inter alia, response to intravitreal MTX measured by time to disappearance of vitreal cells and retinal infiltrates, changes in visual acuity, and clinical recurrence rate. Results: In the past 10 years we have treated 44 eyes of 26 patients; seven patients had monocular involvement, and 19 binocular. Six patients were initially diagnosed as having a non-responsive uveitis, and 16 with either CNS or systemic lymphoma with later involvement of the eye. Four patients had systemic lymphoma; one of them was found to have CNS lymphoma after the ocular involvement. Three patients had T cell lymphoma, and the rest had B cell lymphoma. Clinical remission was reached after 6.4 (3.4) (2–16) injections of MTX (mean (SD) (range)), with 95% of the eyes needing 13 injections or less to be cleared of malignant cells. None of the patients had an intraocular recurrence. Among the side effects, the most common was corneal epitheliopathy, which usually appeared after the third injection and began to subside when the intervals between injections increased. Conclusions: Vitreoretinal involvement of lymphoma can be controlled effectively and without serious adverse reactions by intravitreal MTX injections. The treatment protocol described herein has resulted in no intraocular recurrence so far and has had bearable side effects. The accumulating clinical results bring us to propose the consideration of this protocol as a good first-line treatment option for intraocular lymphoma.

In view of the demanding instruction and training requirements associated with cochlear implantation, patients with cognitive impairments have typically been considered to be poor candidates for this procedure. This presumption persists in part because experience and research in this area are limited. We describe our experience with implanting cochlear devices in 2 patients who had significant psychological impairments; 1 patient had experienced a severe brain injury, and the other had paranoid schizophrenia. Nevertheless, both patients were able to follow the implant training program, and they experienced different degrees of improvement in their hearing. We discuss our preoperative evaluations of these patients and the key factors that led to our decision to proceed with surgery.

Malignant subarachnoid deposits complicate both primary central nervous system (CNS) tumors and systemic neoplasms. Although the pathophysiology of symptoms and signs can not be separated by the category of primary tumors that seeds the leptomeninges, the approach to therapy is not similar in primary CNS tumors and in systemic neoplasms. Standard therapy for subarachnoid seeding in primary CNS tumors include conventional or high doses of systemic chemotherapy with various combinations of radiotherapy given either to limited fields or to the whole neuroaxis. Direct administration of chemotherapy to the CSF is not being used. In contrast, whenever a systemic tumor seeds the subarachnoid space the standard approach includes intensive intra-CSF chemotherapy, radiotherapy to limited or extended CNS fields and various combinations of systemic chemotherapy. The published experience with the conventional therapy is reviewed and is critically analyzed. Evidence indicating that high dose systemic chemotherapy can replace intra-CSF treatment in some subgroups are also reviewed and the rationale for this approach is specified. Recent experience in which intra-CSF therapy was prospectively eliminated from the treatment protocol of leptomeningeal metastases of solid tumors reveals that the response rate and survival are similar to those obtained by protocols that differed only by the inclusion of intra-CSF chemotherapy. Patients who were treated by radiotherapy alone combined with systemic chemotherapy but without the intra-CSF therapy were spared the high rate of early and delayed complications directly related to intra-CSF therapy. Still, treatment outcome did not differ. Therefore, future research efforts and prospective clinical trials should investigate the best chemotherapeutic schedules and their sequencing with radiotherapy or with more intensive complementary systemic chemotherapy schemes. Newly designed drugs with long circulation time and improved CNS penetration may serve for this purpose.

Leptomeningeal metastases are common in patients with metastatic systemic cancer or certain primary brain tumors. They may be unsuspected clinically and may be missed by cerebrospinal fluid (CSF) cytology. We undertook a retrospective study of the diagnostic value of gadolinium enhanced spinal MR imaging in patients with known or at high risk for leptomeningeal metastases (LM).Ninety-six gadolinium enhanced MR examinations of the whole spine were performed in 61 patients (26 primary central nervous system tumors, 20 solid tumors and 15 lymphoproliferative neoplasms). All patients had detailed neurological evaluation and concomitant CSF examination.Sixty-one MR's (62%) were positive, mostly in the lumbar spine. MR's were positive in 92% of patients with positive initial CSF cytology and in 60% of patients with negative CSF cytology. The MR examination was positive in 49% of those without clinical findings related to the spinal region. It showed disease beyond the symptomatic level in 42% of patients with spinal symptomatology. Multi-level spinal involvement was present in 57% of positive MR exams.Enhanced spinal MR is sensitive for the detection of neoplastic spinal seeding. It detects LM in about 50% of high risk patients with negative initial CSF cytology or no spinal symptoms.

We evaluated the role of serotonin (5-HT) in neoplastic cord compression in paraplegic rats harboring a thoracolumbar epidural tumor. We measured serotonin and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in the C-1 to C-7, T-1 to T-6, T-7 to T-12, and T-13 to L-3 spinal segments of tumor-free and tumor-bearing rats. In normal controls, a consistent rostral-to-caudal gradient for 5-HT and 5-HIAA was evident, but the 5-HIAA/5-HT ratio remained constant. In paralyzed rats, 5-HT levels were unchanged, but the 5-HIAA/5-HT ratio was elevated, especially in the compressed segments. Treatment with either dexamethasone or indomethacin delayed onset of paraplegia but had no effect on 5-HT metabolism. Blocking 5-HT receptors by cyproheptadine, evaluated 30 hours after onset of paralysis and treatment, resulted in a reduction in the high water content, vascular permeability, and prostaglandin E2 synthesis in the compressed cord. Early administration of cyproheptadine effectively delayed the onset of paraplegia. These data indicate that receptor-activated serotonergic mechanisms participate in the disruption of the blood-spinal cord barrier and that these effects can be manipulated pharmacologically.