To improve prognosis in recurrent glioblastoma we developed a treatment protocol based on a combination of drugs not traditionally thought of as cytotoxic chemotherapy agents but that have a robust history of being well-tolerated and are already marketed and used for other non-cancer indications. Focus was on adding drugs which met these criteria: a) were pharmacologically well characterized, b) had low likelihood of adding to patient side effect burden, c) had evidence for interfering with a recognized, well-characterized growth promoting element of glioblastoma, and d) were coordinated, as an ensemble had reasonable likelihood of concerted activity against key biological features of glioblastoma growth. We found nine drugs meeting these criteria and propose adding them to continuous low dose temozolomide, a currently accepted treatment for relapsed glioblastoma, in patients with recurrent disease after primary treatment with the Stupp Protocol. The nine adjuvant drug regimen, Coordinated Undermining of Survival Paths, CUSP9, then are aprepitant, artesunate, auranofin, captopril, copper gluconate, disulfiram, ketoconazole, nelfinavir, sertraline, to be added to continuous low dose temozolomide. We discuss each drug in turn and the specific rationale for use- how each drug is expected to retard glioblastoma growth and undermine glioblastoma's compensatory mechanisms engaged during temozolomide treatment. The risks of pharmacological interactions and why we believe this drug mix will increase both quality of life and overall survival are reviewed.

AbstractIntervertebral disc degeneration (IVDD) is one of the common causes of low back pain. Similar to many other multifactorial diseases, it is affected by environmental and genetic factors. Although not completely understood, genetic factors include a wide spectrum of variations, such as single nucleotide polymorphisms, which could play a significant role in the etiology of this disease. Besides, the interactions with environmental factors could make the role of genetic factors more complicated. Genetic variations in disc components could participate in developing degenerative disc disease through altering the normal homeostasis of discs. Gene polymorphisms in disc proteins (collagens I, II, III, IX, and XI), proteoglycans (aggrecan), cytokines (interleukins I, VI, and X), enzymes (matrix metalloproteinases II, III, and IX), and vitamin D receptor seem to play considerable roles in the pathology of this disease. There are also many other investigated genes that could somehow take part in the process. However, it seems that more studies are needed to clarify the exact role of genetics in IVDD.

BackgroundThe aim of this study was to translate the EORTC quality of life questionnaire for brain cancer, the QLQ-BN20, into Persian, and to evaluate its psychometric properties when used among brain cancer patients in Iran.MethodsA standard backward and forward translation procedure was used to generate the Persian language version of the QLQ-BN20. The QLQ-BN20 was administered together with the QLQ-C30 to 194 patients diagnosed with primary brain cancer. Multitrait scaling and confirmatory factor analysis (CFA) were used to evaluate the hypothesized scale structure of the questionnaire. Internal consistency reliability was estimated with Cronbach’s alpha. The ability of the QLQ-BN20 to distinguish between patient subgroups formed on the basis of performance status and cognitive status was evaluated, as was the responsiveness of the questionnaire to changes in performance status over time.ResultsMultitrait scaling and CFA results confirmed the hypothesized scale structure. The measurement model was consistent across men and women. Internal consistency reliability of the multi-item scales ranged from 0.74 to 0.89. The QLQ-BN20 distinguished clearly between patients with relatively good versus poor performance and cognitive status, and changes in scores over time reflected changes observed in performance status ratings.ConclusionsThese results support the validity and reliability of the QLQ-BN20 for use among Iranian patients diagnosed with primary brain cancer. Future studies should examine the psychometrics of the questionnaire when used in patients with brain metastasis.

Polymorphisms of pro-inflammatory cytokine genes could take part in IVDD pathophysiology as the result of alteration in their expression levels or structures. The current study indicated significant roles of TNF-α -308 G/A and TNF-α -238 G/A SNPs with IVDD among Iranian patients. However, this study did not show any significant association between IVDD and either of SNPs of IL-1 and IL-6 genes.

Lipoid proteinosis (LP) is a rare autosomal recessive genodermatosis caused by loss-of-function mutations in the ECM1 gene, and previous studies have noted phenotypic variability. In this study, we examined 12 patients representing three Iranian families for clinical manifestations and genotyped them for mutations in ECM1. LP was diagnosed with characteristic mucocutaneous and neurologic manifestations. Five patients were also subjected to magnetic resonance imaging (MRI)/computed tomography (CT) scan of the central nervous system. DNA was isolated from peripheral blood from patients and their clinically unaffected relatives, and mutations in ECM1 were sought by PCRbased amplification of all exons and flanking intronic sequences, followed by bidirectional Sanger sequencing. Significant phenotypic variability in this multisystem disorder, including presence of convulsions and epilepsy in about half of the patients was noted. In most cases, this was associated with calcifications in the brain detected by MRI/CT scans. Genotyping of the affected individuals in three families from the central region of Iran revealed presence of homozygous c.507delT mutation in ECM1, reflecting the observed consanguinity in these families. This large cohort revealed extensive phenotypic variability in individuals with the same mutation in ECM1. This observation suggests a role for genetic and epigenetic as well as environmental modulation of the phenotype. Identification of mutations allows screening of unaffected individuals for presence or absence of this mutation in extended LP families, with implications for genetic counseling.

PurposeThere are some studies which showed neurofeedback therapy (NFT) can be effective in clients with traumatic brain injury (TBI) history. However, randomized controlled clinical trials are still needed for evaluation of this treatment as a standard option. This preliminary study was aimed to evaluate the effect of NFT on continuous attention (CA) and short-term memory (STM) of clients with moderate TBI using a randomized controlled clinical trial (RCT).MethodsIn this preliminary RCT, seventeen eligible patients with moderate TBI were randomly allocated in two intervention and control groups. All the patients were evaluated for CA and STM using the visual continuous attention test and Wechsler memory scale-4th edition (WMS-IV) test, respectively, both at the time of inclusion to the project and four weeks later. The intervention group participated in 20 sessions of NFT through the first four weeks. Conversely, the control group participated in the same NF sessions from the fifth week to eighth week of the project.ResultsEight subjects in the intervention group and five subjects in the control group completed the study. The mean and standard deviation of participants' age were (26.75 ± 15.16) years and (27.60 ± 8.17) years in experiment and control groups, respectively. All of the subjects were male. No significant improvement was observed in any variables of the visual continuous attention test and WMS-IV test between two groups (p ≥ 0.05).ConclusionBased on our literature review, it seems that our study is the only study performed on the effect of NFT on TBI patients with control group. NFT has no effect on CA and STM in patients with moderate TBI. More RCTs with large sample sizes, more sessions of treatment, longer time of follow-up and different protocols are recommended.

Cerebrovascular disease is one of the leading causes of death in the world, and about one-fourth of cerebrovascular deaths are due to ruptured cerebral aneurysms (CA). Hence it is important to find a way to reduce aneurysm formation and its subsequent morbidity and mortality. Proteolytic activity capable of lysing gelatin has been shown to be increased in aneurysm tissue and expression of plasmin, membrane-type matrix metalloproteinase-1(MT1-MMP), and matrix metalloproteinase-2 (MMP-2) in aneurysmal wall is more than what we observe in normal cerebral arteries. MMP inhibitors such as doxycycline and statins may prohibit aneurysm formation and growth. MMPs are important in tissue remodeling associated with various physiological and pathological processes such as morphogenesis, angiogenesis, apoptosis and tissue repair. In this article we review the role of MMPs and MMP inhibitors in formation of aneurysm.

Intra-operative brain deformation (brain shift) limits the accuracy of image-guided neuro-surgery systems. Ultrasound imaging as a simple, fast and being real time has become an alternative to MR imaging which is an expensive system for brain shift calculation. The main challenges due to speckle noise and artifacts in US images, is to perform an accurate and fast registration of Us images with pre-operative MR images. In this paper an efficient point based registration method based on the alignment of probability density functions called Coherent Point Drift (CPD) is implemented and compared to the conventional ICP method. To perform this, a brain phantom that allows simulating the brain deformation is made. As the results of our phantom study confirm the CPD method clearly outperforms the ICP algorithm for brain shift calculation. Also the result proves that using intra-operative US has led to recover almost 80% of displacement in the region of interest.