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Progress in treating diffuse gliomas remains limited and is principally concerned with the confirmation that cystostatics as nitrosureum derivatives and temozolomide play a role in the treatment of these tumours. At molecular level, diffuse gliomas are a heterogeneous group of tumours. This seems to be an important explanation of why so far no important breakthrough in the treatment of these tumours has been achieved. It is thought that abnormal activation of various molecular signal systems working in parallel in the tumour cell are an important cause of the absence of efficacy of the targeted agents; the inhibition of only one target appears inadequate.

Establishing the presence of paraneoplastic antibodies is important in identifying an often severe neurological syndrome as paraneoplastic and hence directing the search for an underlying neoplasm. A paraneoplastic neurological syndrome was diagnosed in 3 patients. The first was a 64-year-old woman in whom paraneoplastic encephalomyelitis was diagnosed. The diagnosis was strongly supported by a high titre of serum anti-Hu antibodies, despite three negative biopsies from a mediastinal mass. The patient died of a non-convulsive status epilepticus; autopsy revealed not only paraneoplastic encephalomyelitis but also small-cell lung cancer. The second patient was a 55-year-old woman with metastatic breast cancer. After a three-year period of progressive neurological deterioration, a high titre of anti-CV2/CRMP5 antibodies was detected, on the basis of which the clinical syndrome was diagnosed as paraneoplastic. She received immunotherapy and her condition stabilised. The third patient, a 41-year-old man, presented with severe limbic encephalitis. Biopsy from a paraaortic mass was positive for undifferentiated carcinoma. The patient had a high titre ofanti-Ma2 antibodies and was subsequently tested positive for serum alpha-foetoprotein (AFP) and beta-human-chorionic gonadotrophin (bta-HCG). During chemotherapy for a non seminoma testicular cancer, the limbic encephalitis improved both clinically and radiologically, but the patient died as a result of the toxicity of the treatment.

A 78-year-old man with metastasised prostate carcinoma presented with a painless paraparesis. His cerebrospinal fluid showed elevated protein and a mononuclear pleiocytosis, but cytology investigations of 5 separate samples revealed no malignant cells in the cerebrospinal fluid. Extensive viral and bacterial tests (including ELISA for Borrelia burgdorferi) of serum and cerebrospinal fluid were negative. On the day radiation therapy for presumed leptomeningeal metastases was due to start the IgG and IgM Western blot for Borrelia were found to be positive, indicating neuroborreliosis. Soon after the start of antibiotic therapy the paraparesis began to improve and after four weeks the patient had made a complete recovery. In patients with a progressive paraparesis, neuroborreliosis should be considered even in the absence of pain.

A 27-year-old woman with a history of aplastic anaemia complained of poor control of her right arm and hand, unsteady gait, and headache that increased while in a recumbent position. She was diagnosed with cerebral sinus thrombosis. Additional investigation revealed paroxysmal nocturnal haemoglobinuria (PNH). Treatment with heparin was initiated but stopped after the patient developed a brain haemorrhage. The patient recovered with no signs of residual symptoms and began taking oral anticoagulants as maintenance therapy. PNH is a rare acquired clonal disorder due to a defective expression of the glycosylphosphatidyl-inositol anchor membrane protein. It is characterised by haemolytic anaemia, diminished haematopoiesis, increased susceptibility for infections and a hypercoagulable state. Patients with aplastic anaemia have an increased risk of developing PNH. In patients with cerebral sinus thrombosis PNH should be considered as a possible underlying disorder. These patients should be questioned for possible clinical symptoms of PNH, such as acute abdominal pain or dark urine in the morning. For patients with these symptoms and in those with a history of aplastic anaemia or recurrent thrombosis, additional testing for PNH should be conducted.

Objective: To describe the results of the treatment of recurrent glioma with temozolomide., Design: Retrospective., Method: This study evaluated 77 patients with a recurrent high-grade glioma who from August 1997-December 2003 were treated with temozolomide (150-200 mg/m2/day for 5 days per 28-day cycle) following surgery and radiotherapy at the Daniel den Hoed Oncology Centre of the Erasmus MC, Rotterdam, the Netherlands. The patients were divided into 4 groups depending on histology and chemotherapy history., Results: 15 patients received temozolomide for a recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. The response in this group was 80% and after 12 months in 47% of the patients there was no disease progression. 35 patients underwent second-line chemotherapy with temozolomide after earlier chemotherapy with procarbazine, lomustine and vincristine for recurrent anaplastic oligodendroglioma or mixed oligo-astrocytoma. Response was 26% and after 12 months in 15% of patients there was still no disease progression. 14 patients were treated with temozolomide for a recurrent anaplastic astrocytoma with a response of 35% and after 12 months in 8% of these patients there was no disease progression. Of the 13 patients with a recurrent glioblastoma who were treated with temozolomide 16% responded and after 6 and 12 months 21% were still free from progression. Temozolomide was well-tolerated: 2 patients had to stop because of probable side effects. CONCLUSION. Temozolomide has an acceptable safety profile and may be regarded as the preferred treatment for recurrent anaplastic gliomas after radiotherapy. There is only a limited role for temozolomide in the treatment of recurrent glioblastoma.

Objective: A description of clinical features and treatment results in patients with a central nervous system (CNS) localization of systemic non-Hodgkin's lymphoma (NHL)., Design: Retrospective., Setting: Department of Neuro-oncology and Haematology, Daniel den Hoed Cancer Centre, Rotterdam, the Netherlands., Methods: All patients with NHL (but not primary CNS lymphoma) treated in the period January 1st, 1990-December 31st, 1996 at the department of neuro-oncology were reviewed for presence of CNS localizations. Clinical characteristics like malignancy grade, disease stage, presence of extranodal localizations, B-symptoms, serum LDH, neurological signs and symptoms, results of ancillary investigations, treatment and response were recorded., Results: In this period 25 patients were diagnosed with leptomeningeal lymphoma, 2 with an intracerebral lymphoma, and 7 with both. In almost all patients the CNS localization developed during systemic progression of the NHL. Most patients presented with a radicular syndrome, cranial nerve deficits, headache or encephalopathy. More than 80% of the patients showed clinical improvement after treatment with intrathecal chemotherapy, radiation therapy or a combination of both. The median survival was three and a half months, six month survival was 32%. Progression of systemic disease was the most frequent cause of death., Conclusion: In most patients good palliation of neurological signs and symptoms could be obtained with intrathecal chemotherapy and radiation therapy. Survival in these patients was limited, however, in part because of the frequent concurrent progression of systemic disease. Patients with CNS localizations with chemotherapeutic treatment possibilities with a realistic chance of cure or longterm survival should be treated accordingly. Otherwise, treatment should consist of intrathecal chemotherapy or radiation therapy of involved areas only.

Complications of the central nervous system (CNS) are common in systemic autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus (SLE) and primary Sjögren's syndrome. Specific diagnostic tests are lacking and early intervention with immunosuppressive therapy is frequently necessary. Therefore knowledge of these CNS complications is essential for early diagnosis and treatment. Residual cognitive effects were observed in some but not in all tests after prolonged heavy cannabis use. The effects were mostly mild. The relationship of cannabis use, psychotic effects and schizophrenia was unclear; the cannabis conceivably gave relief, but it also appeared that cannabis caused schizophrenia in young people and (or) enhanced the symptoms, especially in young people poorly able to cope with stress or in whom the antipsychotic therapy was unsuccessful.

A 40-year-old man developed cortical blindness during cyclosporin treatment shortly after an allogeneic bone marrow transplantation for chronic myeloid leukaemia. At that time the patient had a therapeutic cyclosporin blood level (226 ng/ml), but a low serum magnesium level and a marginally decreased serum cholesterol level. In addition the patient had hypertension, headache and paraesthesia in the oral, palmar and plantar areas. Vision was fully recovered after discontinuation of the cyclosporin treatment and correction of the hypomagnesaemia. Eighteen cases of cortical blindness during cyclosporin treatment are now known in the literature. Hypomagnesaemia appears to be implicated in the pathogenesis.

In a brain-dead patient, a 42-year-old woman who went into a coma after a cervical foraminotomy, spinal automatisms were seen which cast doubt on the diagnosis of brain death. The procedure which was to lead to organ transplantation was seriously disturbed. In brain-dead patients spinal automatisms appear earlier and are more often present than deep tendon reflexes. Due to the developing hyperreflexia spinal automatisms can be elicited more easily and from a larger skin area as the period of brain death lasts longer. Spinal automatisms can also appear spontaneously and can be generated by hypercapnia. If criteria for brain death are met, these movements are no reason to reconsider the diagnosis of brain death.

The results are presented of a retrospective survey of anterior cervical surgery followed by fusion with autologous bone grafting for the treatment of radiculopathy due to cervical intervertebral disc prolapse or spondylosis. The study included 46 patients, with a follow-up period of at least a year. Follow-up examination was performed by an independent observer. Of the patients 38 (83%) were improved, 34 (74%) having a 'good' or 'excellent' response. Postoperative complications were minor; the most frequent complication was pain or dysaesthesia at the donor site of the bone graft, the iliac crest. It is questionable whether autologous bone grafting is indicated following anterior discectomy.