Background
Intracranial dermoid cysts are uncommon, and their clinical features as well as surgical management differ from patient to patient. Dermoids are generally benign lesions, but may cause ...spontaneous complications such as meningitis and/or hydrocephalus due to rupture and epileptic seizures depending on their location. Little has been reported about characteristic imaging findings with resulting therapeutic considerations, and only a few reports exist about associated hydrocephalus. Imaging modalities have changed and can facilitate differential diagnosis and follow-up if applied correctly. In this paper, we attempt to contribute our clinical experience with the management of dermoid cysts.
Patients and methods
The charts of five men and two women with intracranial dermoid cysts were retrospectively reviewed. The patients were treated between September 1993 and September 2006. Selected patients are presented in detail.
Results
Tumour location, size and radiographic characteristics varied in each patient. Clinical presentations comprised focal neurological deficits as well as epileptic seizures, persistent headache, mental changes and psycho-organic syndromes. One patient underwent delayed ventriculo-peritoneal shunting after ruptured fatty particles caused obstructive hydrocephalus. Despite dermoid rupture into the subarachnoid space, three patients never developed hydrocephalus. Diffuse vascular supra-tentorial lesions were seen in one patient as a result of aseptic meningitis. Diffusion-weighted imaging (DWI) hyperintensity in dermoids is related to decrease of water proton diffusion and should be used for both the diagnosis and follow-up of this lesion.
Conclusion
Although dermoid cysts are known to be benign entities
per se,
their rupture can cause a wide range of symptoms including aseptic meningitis and/or hydrocephalus. This may be due to intraventricular obstruction and/or paraventricular compression. While rupture does not necessarily bring about hydrocephalus, radical removal of the tumour and close monitoring of ventricular size is required. Although not widely recognised as such, DWI is considered to be a useful imaging modality in the diagnosis and follow-up of dermoids.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We have previously reported that combined inhibition of the epidermal growth factor receptor by erlotinib and of RAC1 by NSC23766 yielded a synergistic antiproliferative effect on established and ...primary cultured glioblastoma cells. The current study aimed at identifying the molecular mechanism. Staining for annexin V/PI or carboxyfluorescein succinimidyl ester was performed in order to determine the induction of apoptosis, necrosis or cytostasis in established and primary cultured glioblastoma cells. Moreover, expression of Ki-67 was determined by immunofluorescence, and the expression of cell cycle proteins was analysed by Western blot. Our data show that combined treatment with erlotinib and NSC23766 resulted in a reduced number of cell divisions, a significantly decreased Ki-67 expression, increased apoptosis and autophagy when compared to single agent treatments. On the molecular level, concomitant treatment with both agents resulted in a pronounced downregulation of cyclin D1, cyclin-dependent kinases 2, 4 and 6, as well as of survivin when compared to treatments with either agent alone. In conclusion, we demonstrate that combined treatment of human glioma cell lines in vitro with erlotinib and NSC23766 markedly inhibits cell division, induces apoptosis independent of caspase-3 activation and induces autophagy concomitant with suppression of survivin.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•Brain edema is a common problem during the course of glioblastoma.•Brain edema often requires treatment on its own, separate from specific anti-tumor treatments.•Current first-line treatment is ...dexamethasone or a related corticosteroid.•Use of dexamethasone or related corticosteroid shortens survival.•Three old drugs - the diuretic spironolactone, the anti-bradykinin drug ecallantide, and the antifungal drug clotrimazole each have ancillary attributes that inhibit the edema forming process in glioblastoma.
This paper presents a short review of data supporting a dexamethasone sparing regimen, SEC, to reduce glioblastoma related brain edema. The conclusion of the reviewed data is that the rationale and risk/benefit ratio favors a pilot study to determine if the three drug regimen of SEC can reduce need for corticosteroid use during the course of glioblastoma. Details of how selected pathophysiological aspects of brain edema occurring during the course of glioblastoma and its treatment intersect with the established action of the three old drugs of SEC indicate that they can be repurposed to reduce that edema. Current first-line treatment of this edema is dexamethasone or related corticosteroids. There are multiple negative prognostic implications of both the edema itself and of dexamethasone, prime among them shortened survival, making a dexamethasone sparing regimen highly desirable. SEC uses spironolactone, an antihypertensive potassium-sparing diuretic acting by mineralocorticoid receptor inhibition, ecallantide acting to inhibit kallikrein activation marketed to treat hereditary angioedema, and clotrimazole, an old antifungal drug that inhibits intermediate conductance Ca++ activated K+ channel (KCa3.1). These three old drugs are well known to most clinicians, have a well-tolerated safety history, and have a robust preclinical database showing their potential to reduce the specific edema of glioblastoma. Additionally, these three drugs were chosen by virtue of each having preclinical evidence of glioblastoma growth and/or migration inhibition independent of their edema reduction action. A clinical study of SEC is being planned.
Cet article présente un brève aperçu des recherches précédentes soutenant un régime d’épargne de la dexaméthasone, SEC, pour réduire l’œdème cérébral lié au glioblastome. La conclusion de ces recherches ici examinées, est que la justification et le rapport bénéfice/risque favorisent une étude pilote pour déterminer si le régime à trois médicaments de la SEC peut réduire le besoin de corticostéroïdes au cours du glioblastome. Le traitement actuel de première intention est la dexaméthasone ou des corticostéroïdes apparentés. Bien qu’une telle utilisation de la dexaméthasone soit sûre et efficace à court terme, il existe de multiples implications pronostiques négatives à la fois de l’œdème lui-même et de la dexaméthasone, parmi lesquelles une survie raccourcie, ce qui rend un régime d’épargne de la dexaméthasone hautement souhaitable. Les trois médicaments du SEC sont i) spironolactone, un diurétique antihypertenseur épargneur de potassium agissant par inhibition des récepteurs minéralocorticoïdes, ii) l’écallantide, un inhibiteur d’activation de la kallicréine commercialisé pour traiter l’angio-œdème héréditaire, et iii) clotrimazole, un ancien antifongique qui inhibe la conductance intermédiaire du canal K+ activé par Ca++ (KCa3.1). Ces trois médicaments sont bien connus de la plupart des cliniciens, ont des antécédents d’innocuité bien tolérés et disposent d’une base de données préclinique ou clinique montrant leur potentiel à réduire l’œdème spécifique du glioblastome. De plus, ces trois médicaments ont été choisis en vertu du fait que chacun présentait des preuves précliniques de l’inhibition de la migration ou de la croissance du glioblastome indépendamment de leur action de réduction de l’œdème. Une étude clinique de la SEC est en cours de planification.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Among the various causes of vertigo, the so-called cervicogenic vertigo (CV) has been the most controversial. However, perturbations of proprioceptive signals and abnormal activity of the cervical ...afferents can induce vertigo. Medial branch blocks (MBBs) are a diagnostic tool designed to test whether a patient's neck pain is mediated by one or more of the medial branches of the dorsal rami of the spinal nerve. It is unknown whether MBBs are also suitable for testing symptoms other than pain.
The purpose of this study was to test whether MBBs of the cervical spine can be used as a diagnostic tool to identify patients with CV.
A retrospective practice audit (clinical observation).
An interventional pain management and spine practice.
An electronic medical record system was used to identify patients in a single spine center. Included were consecutive patients with neck pain and vertigo, who had received cervical MBBs in a period from July 2001 to April 2016. The patients were tested with a MBB of about 1 mL of bupivacaine (0.25%) and 20 mg triamcinolone. Injections were performed with fluoroscopic visualization using established techniques in 2 or 3 levels on one or both sides. Vertigo was analyzed through the global clinical impression of the patient (i.e., "gone," "better," "the same," or "worse").
One-hundred seventy-eight patients met the inclusion criteria. One-hundred eleven patients (62.4%) experienced a significant improvement of the vertigo. In 47 patients (26.4%), no information about the vertigo was available at follow-up; these patients were assumed to have no improvement (worst-case scenario). Hence, altogether 67 patients (37.6%) had a negative result. The median relief of the vertigo was 2 months. Differences in age, gender, level of treatment, or pain duration between patients with relief of the vertigo and without relief were not found. Nine patients with a whiplash injury in their medical history were also tested. They experienced a lower success rate and had longer duration of pain before the treatment; however, these differences are not statistically significant.
It was the primary intention to treat neck pain; the assessment of vertigo was an additional aim. Therefore, the history taken and the clinical examination were not targeted specifically to vertigo. A placebo effect cannot be excluded. Further studies with the primary focus on CV are necessary to prove the significance of MBBs.
This is the first study to demonstrate that MBBs of the cervical spine can be a useful tool for the diagnosis of CV, because they temporarily block cervical afferents. In 63.4% of patients with neck pain and suspected CV, the vertigo was significantly improved. Further placebo-controlled studies with the primary intention on CV are necessary to prove the significance of MBBs.
Cervicogenic vertigo, medial branch block, facet joint, zygapophysial joint, neck pain, differential diagnosis.
CUSP9 treatment protocol for recurrent glioblastoma was published one year ago. We now present a slight modification, designated CUSP9*. CUSP9* drugs--aprepitant, artesunate, auranofin, captopril, ...celecoxib, disulfiram, itraconazole, sertraline, ritonavir, are all widely approved by regulatory authorities, marketed for non-cancer indications. Each drug inhibits one or more important growth-enhancing pathways used by glioblastoma. By blocking survival paths, the aim is to render temozolomide, the current standard cytotoxic drug used in primary glioblastoma treatment, more effective. Although esthetically unpleasing to use so many drugs at once, the closely similar drugs of the original CUSP9 used together have been well-tolerated when given on a compassionate-use basis in the cases that have come to our attention so far. We expect similarly good tolerability for CUSP9*. The combined action of this suite of drugs blocks signaling at, or the activity of, AKT phosphorylation, aldehyde dehydrogenase, angiotensin converting enzyme, carbonic anhydrase -2,- 9, -12, cyclooxygenase-1 and -2, cathepsin B, Hedgehog, interleukin-6, 5-lipoxygenase, matrix metalloproteinase -2 and -9, mammalian target of rapamycin, neurokinin-1, p-gp efflux pump, thioredoxin reductase, tissue factor, 20 kDa translationally controlled tumor protein, and vascular endothelial growth factor. We believe that given the current prognosis after a glioblastoma has recurred, a trial of CUSP9* is warranted.
Intraoperative magnetic resonance imaging is a widely accepted method for resection control of glial tumors. Increasingly, it is also used during the resection of skull base tumors. Several studies ...have independently demonstrated an increase in the extent of resection in these tumors with improved prognosis for the patients. Technical innovations combined with the easier operation of this imaging modality have led to its widespread implementation. The development of digital image processing has also brought other modalities such as ultrasound and computed tomography to the focus of skull base surgery.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
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