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We present here a potential new treatment adjunct for glioblastoma. Building on murine studies, a series of papers appeared recently showing that therapeutic irradiation of the ipsilateral subventricular zone (SVZ) retards growth of more peripherally growing cortical glioblastomas in humans, suggesting a tumor trophic function for the SVZ. Further studies showed that SVZ cells migrate out towards a peripheral glioblastoma. Dopamine signaling through D3 subtype receptor indirectly drives this centrifugal migration in humans. Since psychiatry has several drugs with good D3 blocking attributes, such as fluphenazine, or perphenazine, we suggest that adding one of these D3 blocking drugs to current standard treatment of resection followed by temozolomide and irradiation might prolong survival by depriving glioblastoma of the trophic functions previously subserved by dopaminergic signaling on SVZ cells. [ABSTRACT FROM AUTHOR]

Lopez-Gomez et al. recently published remarkable but mechanistically unexplained empirical evidence that the old antibiotic dapsone has antiepileptic activity. We addressed the question 'Why should a sulfone antibiotic reduce seizures?'. We report here our conclusions based on data from past studies that seizures are associated with elevated interleukin-8 (IL-8) and that dapsone inhibits IL-8 release and function in several different clinical and experimental contexts. Diverse CNS insults cause an increase in CNS IL-8. Thus, the pro-inflammatory environment generated by increase IL-8 leads to a lower seizure threshold. Together this evidence indicates dapsone exerts anti-seizure activity by diminishing IL-8 signalling. Since IL-8 is clearly upregulated in glioblastoma and contributes to the florid angiogenesis of that disease, and since interference with IL-8 function has been shown to inhibit glioblastoma invasion and growth in several experimental models, and dapsone has been repeatedly been shown to clinically inhibit IL-8 function when used to treat human neutrophilic dermatoses, we believe that dapsone thereby reduces seizures by countering IL-8 function and may similarly retard glioblastoma growth by such anti-IL-8 function. [ABSTRACT FROM AUTHOR]

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As current treatments for glioblastoma commonly fail to cure, the need for more effective therapeutic options is overwhelming. Here, we summarize experimental evidence in support of the suggestion that metformin and olanzepine have potential to enhance the cytotoxic effects of temozolomide, an alkylating chemotherapeutic agent commonly used to treat glioblastoma. Although the primary path leading to temozolomide-induced cell death is formation of O-6-methylguanine and apoptotic signalling triggered by O-6-methyl G:T mispairs, that apoptotic signalling goes through a step mediated by AMP-activated protein kinase (AMPK). Metformin or olanzapine have been shown independently to enhance AMPK activation. Metformin to treat diabetes and olanzapine to treat psychiatric disorders are well tolerated and have been used clinically for many years. Thus it should be feasible to increase AMPK activation and add to the pro-apoptotic effects of temozolomide, by adding metformin and olanzapine to the therapeutic regimen. Clinical assessment of the potential benefit of such combined therapy against glioblastoma is warranted. [ABSTRACT FROM AUTHOR]

Intrinsic brainstem tumours in adults have a poor prognosis and surgical resection is rarely performed. Encouraged by successful operations on children performed in our department, we began a more aggressive strategy of open operations. Between 1986 and 1997, we operated upon 16 consecutive patients over 16 years of age (five female, 11 male, mean age 36.9 years) who were suffering from intrinsic tumours located in the pons and/or medulla oblongata. The extent of first open resection was 80 – 100% in two of the cases and more than 50% in nine cases. The mean survival time after the first occurrence of symptoms was 88.1 (median 34.5) months, and 39.9 (median 11) months after the first open operation. The rate of 5-year survival from the first occurrence of symptoms was 37.5% (25% after the first open surgical procedure). Thirteen out of 16 patients died within the follow-up period of at least 6.3 years, two of them within the immediate postoperative period. Eleven patients experienced a postoperative deterioration of symptoms from which only four recovered. Eight patients had from WHO grade II astrocytoma and a similar course as patients with higher-grade gliomas (n = 4). Our results indicate that open microneurosurgery for intrinsic brainstem tumours is of questionable benefit for the patient. Although surgery offers the advantages of reliable confirmation of histopathology and may be associated with prolonged survival, neurological deterioration was common and, unlike in paediatric patients, often irreversible. [ABSTRACT FROM AUTHOR]

Background The first gravitational valve, the Cordis-Hakim-Lumbar (CHL) was patented in 1975. In 1980 the author assisted two implantations in LP-shunts, but similar to all contemporary neurosurgeons he does not recognise the technical breakthrough. In spite of a brilliant concept the CHL flopped, probably due to the exclusive design for the rare lumbar shunts (transversal connectors) and a round valve body with a strong tendency to rotate in the lumbar fat and resulting dysfunctions. Fred Jackson, the initiator of the first large series in the USA died by an aircrash in 1980; his encouraging results were never published. In 1989 the CHL was tested with excellent results by Richard and us. As the first we proposed the combination with adjustable valves on 91 and implanted a modified CHL with a Medos-P in 83. We conceived longitudinal valve bodies, which stimulated the development of Cordis GCA and Miethke Shunt Assistant (94). Independently the Chhabra Z-Flow, the Sophysa AS and the Affeld-valve, a precursor of the Miethke Dual-Switch, were developed. Materials and methods Retrospective study on 420 patients treated with Cordis Hakim-Lumbar or -GCA, Miethke ShuntAssistant, -DualSwitch, -Paedi/GAV and ProGAV. Follow-up since 1984. Results The overdrainage was reduced: Only 5/420 patients required surgery due to subdurals (1.2%); 6 other mild hygromas disappeared conservatively. Of 11 chronic hematomas, five were caused by significant head traumata, two by incorrect (diagonal) valve placement, one by inadequate pressure selection and one by pneumatocephalus. We counted only two valve related "real failures" with consecutive cSDHs. Of 110 NPH-patients two only (1.8%) presented hygromas. The quote of infections, catheter problems and valve dysfunctions met standard experiences. Conclusion Gravitational valves have largely solved the problems of overdrainage. However, residual problems such as the adaptation on the growth of children or high abdominal counter pressure in adipous patients with resulting underdrainage require further improvements, especially adjustable g-valves. The current state-of-the-art is the crossover of adjustable and gravitational valves. [ABSTRACT FROM AUTHOR]