Nikolaos Foroglou

Decompressive craniectomy for the management of patients with refractory hypertension: should it be reconsidered?

Summary.Summary. Introduction: The management of refractory post-traumatic cerebral oedema remains a frustrating endeavor for the neurosurgeon and the intensivist. Mortality and morbidity rates remain high, despite refinements in medical and pharmacological means of controlling intracranial hypertension. Method and Material: In this retrospective study we have evaluated the efficacy of decompressive craniectomy as a last resort therapy, from the data of nine patients with severe brain injury and delayed cerebral oedema (diffuse injury type III), treated between January 1997 and September 1999. The following parameters were considered: age, Glascow Coma Scale, injury severity, intracranial pressure, CT findings, pupil reaction/posturing. Follow-up period was over at least 2 years and outcome measured on the GOS. Results: Patients have been operated on post-trauma median day 3, mean age 26±9, GCS 7±3.7, mean APACHE II 16±6.4, mean ISS 27.8±16.1, mean preoperative ICP 37.7±10.0, mean postoperative ICP 18.1±16.01. Seven patients have been operated by a frontotemporoparietal approach (six of them bilateral, one unilateral) and two patients have been operated on by a bilateral subtemporal approach. Mortality rates 22%, severe disability 11%, good recovery 66%. Discussion: Patients with STBI, developing delayed intracranial hypertension caused by diffuse cerebral oedema, definitely benefit from craniectomy when current medical treatment has failed. The encouraging results of outcome in this and more recent studies, indicate the need for a multi-institutional randomized prospective study evaluating early indicators of raised ICP, timing, efficacy of treatment, operative technique and complications of decompressive craniectomy.

Linezolid Penetration Into Cerebrospinal Fluid and Brain Tissue

Abstract The aim of the study was to evaluate the penetration of linezolid into cerebrospinal fluid (CSF) and brain tissue after a single i.v. dose of 600 mg. The penetration of linezolid into cerebrospinal fluid and brain tissue was studied in 18 patients undergoing a neurosurgical procedure. Linezolid 600 mg i.v. was given with the induction of anesthesia. Mean concentrations of linezolid 2h after the final dose, in serum, cerbrospinal fluid and brain tissue were assayed by HPLC. CSF/serum and brain/serum ratios were 69.57% and 44.66% respectively. Concentrations of linezolid were above the MIC90s for staphylococci and streptococci. The concentrations obtained indicate good penetration of linezolid into CSF and brain tissue and support its use in the management of multidrug-resistant Gram-positive CNS infections.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty‐six epilepsy centers and members of “E‐PILEPSY” (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co‐normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Tones and numbers: a combined EEG-MEG study on the effects of musical expertise in magnitude comparisons of audiovisual stimuli.

This study investigated the cortical responses underlying magnitude comparisons of multisensory stimuli and examined the effect that musical expertise has in this process. The comparative judgments were based on a newly learned rule binding the auditory and visual stimuli within the context of magnitude comparisons: “the higher the pitch of the tone, the larger the number presented.” The cortical responses were measured by simultaneous MEG\EEG recordings and a combined source analysis with individualized realistic head models was performed. Musical expertise effects were investigated by comparing musicians to non‐musicians. Congruent audiovisual stimuli, corresponding to the newly learned rule, elicited activity in frontotemporal and occipital areas. In contrast, incongruent stimuli activated temporal and parietal regions. Musicians when compared with nonmusicians showed increased differences between congruent and incongruent stimuli in a prefrontal region, thereby indicating that music expertise may affect multisensory comparative judgments within a generalized representation of analog magnitude. Hum Brain Mapp 35:5389–5400, 2014.

Expression pattern of the Hedgehog signaling pathway in pituitary adenomas

Several studies have demonstrated the role of Wnt and Notch signaling in the pathogenesis of pituitary adenomas, but data are scarce regarding the role of Hedgehog signaling. In this study we investigated the differential expression of gene targets of the Hedgehog signaling pathway. Formalin-fixed, paraffin-embedded specimens from adult patients who underwent transphenoidal resection and normal human pituitary tissues that were obtained from autopsies were used. Clinical information and data from pre-operative MRI scan (extracellular tumor extension, tumor size, displacement of the optic chiasm) were retrieved from the Hospitals database. We used a customized RT(2) Profiler PCR Array, to investigate the expression of genes related to Notch and Hedgehog signaling pathways (PTCH1, PTCH2, GLI1, GLI3, NOTCH3, JAG1, HES1, and HIP). A total of 52 pituitary adenomas (32 non-functioning adenomas, 15 somatotropinomas and 5 prolactinomas) were used in the final analysis. In non-functioning pituitary adenomas there was a significant decrease (approximately 75%) in expression of all Hedgehog related genes that were tested, while Notch3 and Jagged-1 expression was found significantly increased, compared with normal pituitary tissue controls. In contrast, somatotropinomas demonstrated a significant increase in expression of all Hedgehog related genes and a decrease in the expression of Notch3 and Jagged-1. There was no significant difference in the expression of Hedgehog and Notch related genes between prolactinomas and healthy pituitary tissues. Hedgehog signalling appears to be activated in somatotropinomas but not in non-functioning pituitary adenomas in contrast to the expression pattern of Notch signalling pathway.

Lumbar puncture complicated by spinal epidural hematoma in a child with leukemia

We report a case of spinal epidural hematoma (SEH) preceded by diagnostic lumbar puncture (LP) in a 5‐year‐old boy with acute lymphoblastic leukemia. MRI confirmed the presence of SEH between T7 and L5 levels, but the patient showed fast recovery during the next hours and conservative management was elected.

Pituitary apoplexy following endoscopic sinus surgery

OBJECTIVE To highlight the possibility of pituitary apoplexy after functional endoscopic sinus surgery for elimination of sinonasal infection, an important preparatory step for safe trans-sphenoidal access to the pituitary fossa. CASE REPORT A 67-year-old man with a known pituitary macroadenoma developed headache, diplopia and reduced vision after endoscopic middle meatal antrostomy and ethmoidectomy for rhinosinusitis with polyps. Magnetic resonance imaging showed pituitary haemorrhage. The patient underwent emergency endoscopic trans-sphenoidal resection of the tumour, with significant symptomatic improvement. Despite mild right eyelid ptosis and persistent diabetes insipidus, the patient resumed normal activities in a few weeks. To our knowledge, this is the first report of pituitary apoplexy after a nasal operation. CONCLUSION Pituitary apoplexy is a rare and potentially life-threatening event in high risk patients with pituitary adenomas; it may occur spontaneously or after surgical procedures. Early, combined surgical intervention by rhinologists and neurosurgeons is recommended. The endoscopic trans-sphenoidal approach is a safe and effective technique for the acute management of pituitary apoplexy.

Somatostatin Analogue Treatment of a TSH-Secreting Adenoma Presenting With Accelerated Bone Metabolism and a Pericardial Effusion: A Case Report

AbstractIncreased bone turnover and other less frequent comorbidities of hyperthyroidism, such as heart failure, have only rarely been reported in association with central hyperthyroidism due to a thyrotropin (TSH)-secreting pituitary adenoma (TSHoma). Treatment is highly empirical and relies on eliminating the tumor and the hyperthyroid state.We report here an unusual case of a 39-year-old man who was initially admitted for management of pleuritic chest pain and fever of unknown origin. Diagnostic work up confirmed pericarditis and pleural effusion both refractory to treatment. The patient had a previous history of persistently elevated levels of alkaline phosphatase (ALP), indicative of increased bone turnover. He had also initially been treated with thyroxine supplementation due to elevated TSH levels. During the diagnostic process a TSHoma was revealed. Thyroxine was discontinued, and resection of the pituitary tumor followed by treatment with a somatostatin analog led to complete recession of the effusions, normalization of ALP, and shrinkage of pituitary tumor.Accelerated bone metabolism and pericardial and pleural effusions attributed to a TSHoma may resolve after successful treatment of the tumor. The unexpected clinical course of this case highlights the need for careful long-term surveillance in patients with these rare pituitary adenomas.

Calpain-Dependent Death in C6 Rat Glioma Cells, Exhibiting a Synergistic Effect with Temozolomide

Abstract Crocus sativus L., a dietary herb, has been used for various diseases including cancer. This is an in vitro study investigating the antineoplastic effect of the extract of the plant against C6 glioma rat cell line. The mechanism of cellular death and the synergistic effect of the extract with the alkylating agent temozolomide (TMZ) were investigated. Cellular viability was examined in various concentrations of the extract alone or in combination with TMZ. Apoptosis was determined with flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and autophagy by western blotting of the light chain 3 (LC3)-II. Cellular viability was reduced after exposure to the extract with half maximal inhibition concentration at 3 mg/ml. Flow cytometry and TUNEL assay suggested that the extract does not induce apoptosis. Moreover, their combination increased the ratio dead/apoptotic cells 10-fold (P < 0.001). LC3-II protein levels reduced after Crocus extract while this effect was reversed when the calpain inhibitor MDL28170 was added, suggesting a calpain-dependent death possibly through autophagy. We concluded that the extract of Crocus increases dead cell number after 48 h of exposure. Our results suggest that the cell undergoes calpain-dependent programmed cell death while co-exposure to Crocus extract and TMZ enhances the antineoplastic effect of the latter.

Does proximity to the subventricular zone and expression of CXCR-4 and nestin affect prognosis in high-grade glioma?

Abstract Background: It is suspected that infiltration of stem cell areas with high-grade glioma (HGG) generates a population that compromises treatment results and survival. In this prospective study we set to assess the prognostic value of the proximity of the contrast-enhancing lesion (CEL) on MRI to the subventricular zone (SVZ) and the expression of CXCR4 and nestin as potential factors in the stem cell migration pathway. Method: All patients diagnosed with high-grade glioma over a three-year period from a single institution were enrolled in this prospective study. Based on MRI preoperative findings, the patients were classified into 4 Groups (I–IV) according to the proximity of the CEL on MRI to the SVZ. Histological samples were assessed with immunohistochemistry for nestin and CXCR4. Classification into groups and the presence of nestin and CXCR4 were evaluated as predictive factors for overall (OS) and progression free survival (PFS). Results: Fourty patients were included in the study. In multivariate analysis, Groups II, III and IV predicted longer OS in comparison to group I (p = 0.01; p < 0.01; p < 0.01 respectively) and group III and IV predicted longer OS in comparison to group II (p < 0.01; p = 0.04 respectively). Group III predicted longer PFS than group I and II (p = 0.01; p < 0.01 respectively). The expression rates of CXCR-4 and nestin could not predict OS or PFS. Conclusions: In our study the classification according to the proximity of the contrast enhancing part of the lesion and the SVZ proved to be prognostically significant for both OS and PFS. Presence of CXCR4 or nestin was not predictive for OS or PFS.