Theodosis Kalamatianos

PlGF and sVEGFR-1 in chronic subdural hematoma: implications for hematoma development

OBJECT A considerable body of evidence indicates that inflammation and angiogenesis play a significant role in the development and progression of chronic subdural hematoma (CSDH). While various experimental and clinical studies have implicated placental growth factor (PlGF) in the processes that underpin pathological angiogenesis, no study has thus far investigated its expression in CSDH. The actions of PlGF and its related proangiogenic vascular endothelial growth factor (VEGF) are antagonized by a high-affinity soluble receptor, namely soluble VEGF receptor-1 (sVEGFR-1), and thus the ratio between sVEGFR-1 and angiogenic factors provides an index of angiogenic capacity. METHODS In the present study, using an automated electrochemiluminescence assay, levels of PlGF and sVEGFR-1 were quantified in serum and hematoma fluid obtained in 16 patients with CSDH. RESULTS Levels of PlGF and sVEGFR-1 were significantly higher in hematoma fluid than in serum (p < 0.0001). In serum, levels of sVEGFR-1 were higher than those of PlGF (p < 0.0001), whereas in hematoma fluid this difference was not apparent. Furthermore, the ratio of sVEGFR-1 to PlGF was significantly lower in hematoma fluid than in serum (p < 0.0001). CONCLUSIONS Given previous evidence indicating a role for PlGF in promoting angiogenesis, inflammatory cell chemotaxis, and stimulation, as well as its ability to amplify VEGF-driven signaling under conditions favoring pathological angiogenesis, enhanced expression of PlGF in hematoma fluid suggests the involvement of this factor in the mechanisms of inflammation and angiogenesis in CSDH. Furthermore, a reduced ratio of sVEGFR-1 to PlGF in hematoma fluid is consistent with the proangiogenic capacity of CSDH. Future studies are warranted to clarify the precise role of PlGF and sVEGFR-1 in CSDH.

Twelve-Year Hospital Outcomes in Patients with Idiopathic Hydrocephalus

OBJECTIVE The aim of this study was to examine patients who were admitted for the first-ever shunting for idiopathic normal pressure hydrocephalus (INPH) during a 12-year period, in terms of variation rate, patient demographic characteristics, shunt procedures, postoperative complications, and hospital outcome. METHODS An electronic database which included all shunted patients (1998 to 2009) was used to retrieve demographic, clinical, and hospital outcome data. INPH patient identification was based on clinical and imaging diagnostic criteria. RESULTS INPH patients (n = 238) who had undergone shunting were identified. The mean age and male to female ratio of INPH patients were 73.3 (± 7) years and 1.28:1, respectively.The number of surgically managed INPH cases and proportion of INPH-related shunting procedures rose consecutively during the second and last third of the study period. Ventriculoperitoneal shunts (n = 129; 54.2%) were the most commonly used configurations, followed by ventriculoatrial (n = 108; 45.4%) and lumboperitoneal (n = 1; 0.4%). Intrahospital shunt-related complications were hematomas (0.84%), meningitis (0.42%), and status epilepticus (0.42%). A favorable outcome was reported for 66.8% of patients; 31.5% showed no change. Overall inpatient mortality was 1.7%. CONCLUSION The quantitative findings indicate a progressive rise in the number of surgically managed INPH patients that parallels a rise in the proportion of INPH-related shunting procedures. Contributing factors are likely to include improved diagnosis and an increase in awareness of the INPH syndrome by referring physicians.

Neck pain in a sample of Greek urban population (fifteen to sixty-five years): analysis according to personal and socioeconomic characteristics.

Study Design. A cross-sectional study of neck pain and its related aspects in a sample of Greek urban population (15–65 years). Objective. To estimate the prevalence of neck pain in a Greek urban population (15–65 years) and to study the association of neck pain with several socioeconomic and demographic characteristics. Summary of Background Data. The results of several prevalence studies carried out in different populations indicate a high frequency of neck pain in the general population. Socioeconomic and demographic factors are likely to influence neck pain frequency and neck pain–associated burden. Methods. A 1000-person sample of the general Greek population (15–65 years) living in the Greek capital and other urban centers of the country was selected by multiple-stage sampling, with definition of sample quotas based on demographic characteristics. Data on neck pain and its related aspects, including healthcare utilization, as well as demographic, socioeconomic, and employment data, were collected through personal interviews. Results. Of the 204 individuals who reported neck pain during the last month, 35 (17.2%) consulted a physician, 72 (35.3%) received medication, and 15 (7.4%) stayed in bed for some time, during this period and because of neck pain. The mean duration of pain for individuals who reported neck pain during the last month was 12 days. A total of 8.6% of working individuals who experienced neck pain during the last month reported work absenteeism due to this pain, during this period; the mean duration of absence was 4.6 days. Neck pain frequency was related to several sociodemographic factors. Female sex, increased age, and being married showed a statistically significant association with the presence of neck pain. Conclusion. The present results indicate that neck pain is a common symptom in the studied Greek urban population. Nevertheless, relatively few individuals seek medical advice for this symptom. Neck pain frequency is associated with age, sex, and marital status.

The Evangelismos hospital central nervous system tumor registry: Analysis of 1414 cases (1998-2009)

Background: The Evangelismos Hospital central nervous system (CNS) Tumor Registry represents the current effort of the Departments of Neurosurgery and Pathology to collect data for primary and metastatic CNS tumor patients. In the present study, 12-year hospital data (1998-2009) were reviewed and analyzed. Methods: Patients that underwent surgery for CNS tumors for the first time were identified. Histologically confirmed tumor rates by age and gender were compared. Time trends in annual rates for specific tumor types were investigated. In-hospital mortality rates and length of hospital stay were analyzed by age and gender and their putative variations across the study period investigated. Results: A total of 1414 patients (age 15-89 years) were identified. The most frequently encountered histologies were gliomas and meningiomas, accounting for, respectively, 32.8% and 29.1% of the total sample. A greater proportion of meningiomas was found in women; the proportion of glioblastomas and metastatic tumors, as well as of mixed gliomas, were greater in men. Increased rates of glioblastoma and meningioma with advancing age at diagnosis were also apparent. There were no significant variations in time trends for specific tumor types. In-hospital mortality was significantly higher for older patients (≥70 years). An increase in the length of hospital stay was apparent between the first and middle third of the study period. Conclusions: Analysis of tumor rates in relation to age at diagnosis and gender showed significant bias in accordance with salient literature. Available data indicated no significant variations in time trends for specific tumor types across the study period, while an adverse effect of advanced age on in-hospital mortality was shown. The present findings can guide the formulation of future treatment programs and preventive strategies and provide the basis for further intra- and/or interdepartmental research.

Maternal environmental risk factors for congenital hydrocephalus: a systematic review

OBJECTIVE Congenital hydrocephalus (CH) is one of the most frequent CNS congenital malformations, representing an entity with serious pathological consequences. Although several studies have previously assessed child-related risk factors associated with CH development, there is a gap of knowledge on maternal environmental risk factors related to CH. The authors have systematically assessed extrinsic factors in the maternal environment that potentially confer an increased risk of CH development. METHODS The Cochrane Library, MEDLINE, and EMBASE were systematically searched for works published between 1966 and December 2015 to identify all relevant articles published in English. Only studies that investigated environmental risk factors concerning the mother-either during gestation or pregestationally-were included. RESULTS In total, 13 studies (5 cohorts, 3 case series, 3 case-control studies, 1 meta-analysis, and 1 case report) meeting the inclusion criteria were identified. Maternal medication or alcohol use during gestation; lifestyle modifiable maternal pathologies such as obesity, diabetes, or hypertension; lack of prenatal care; and a low socioeconomic status were identified as significant maternal environmental risk factors for CH development. Maternal infections and trauma to the mother during pregnancy have also been highlighted as potential mother-related risk factors for CH. CONCLUSIONS Congenital hydrocephalus is an important cause of serious infant health disability that can lead to health inequalities among adults. The present study identified several maternal environmental risk factors for CH, thus yielding important scientific information relevant to prevention of some CH cases. However, further research is warranted to confirm the impact of the identified factors and examine their underlying behavioral and/or biological basis, leading to the generation of suitable prevention strategies.

Approaching the Atrium Through the Intraparietal Sulcus: Mapping the Sulcal Morphology and Correlating the Surgical Corridor to Underlying Fiber Tracts

BACKROUND Although the operative corridor used during the intraparietal transsulcal approach to the atrium has been previously investigated, most anatomical studies focus on its relationship to the optic radiations. OBJECTIVE To study the intraparietal sulcus (IPS) morphology and to explore the subcortical anatomy with regard to the surgical trajectory used during the intraparietal transsulcal tranventricular approach. METHODS Twenty-five adult, formalin fixed, cerebral hemispheres were investigated. Fifteen underwent the Klingler procedure and were dissected in a lateromedial direction using the fiber microdissection technique. The trajectory of the dissection resembled that of real operative settings. The remaining 10 hemispheres were cut along the longitudinal axis of the sulcus in order to correlate its surface anatomy to corresponding parts of the ventricular system. RESULTS IPS demonstrated an interrupted course in 36% of the specimens while its branching pattern was variable. The sulcus anterior half was found to overly the atrium in all occasions. Four discrete, consecutive white matter layers were identified en route to the atrium, ie, the arcuate fibers, the arcuate segment of the superior longitudinal fasciculus, the corona radiata and tapetum, with the arcuate segment being near to the dissection trajectory. CONCLUSION Given the angle of brain transgression during the intraparietal approach, we found the optimal dissection area to be the very middle of the sulcus. The IPS-postcentral sulcus meeting point, in contrast to previous thought, proved to risk potential injury to the arcuate segment of the superior longitudinal fasciculus, thus affecting surgical outcome.

Anaplastic lymphoma kinase expression and gene alterations in glioblastoma: correlations with clinical outcome

Aims To study anaplastic lymphoma kinase (ALK) protein expression and possible underlying gene alterations in glioblastoma (GBM), correlating them with clinical outcome. Methods We studied ALK immunohistochemical expression and fluorescent in situ hybridisation (FISH)-detected ALK gene alterations in 51 GBMs (46 isocitrate dehydrogenase-1 (IDH1)R132H-negative and 5 IDH-mutant (IDH1R132H-positive)). We compared two anti-ALK antibodies and immunohistochemical detection systems (5Α4/Nichirei Biosciences, D5F3/Ventana). The results were correlated with tumour cell proliferation and clinical outcome. Results Intense granular cytoplasmic ALK immunostaining was observed in 10/51 (19.61%) GBM and correlated with high Ki67 proliferation index; only 1 in 10 ALK-positive cases displayed multiple alk gene signals by FISH. Moderate ALK immunostaining was observed in 21 (41.17%), weak immunostaining in 5 (9.80%) while 15 (29.42%) cases were negative. p53 was expressed in 26/51 GBM (50.9%) (10% cut-off). IDH1R132H-negative GBM showed higher ALK expression compared with IDH-mutant GBM (65.2% vs 20%). ALK overexpression was more common in older patients but did not correlate with other clinicopathological variables or patient overall survival. Conclusions ALK overexpression can be identified in up to 70% of GBMs and does not correlate with underlying alk gene amplification. Despite being more common in rapidly growing, clinically aggressive GBM, ALK overexpression did not show correlation with prognosis in this study.

Finger tapping and verbal fluency post-tap test improvement in INPH: its value in differential diagnosis and shunt-treatment outcomes prognosis

BackgroundIdiopathic normal pressure hydrocephalus (INPH) diagnosis is challenging as it can be mimicked by other neurological conditions, such as neurodegenerative dementia and motor syndromes. Additionally, outcomes after lumbar puncture (LP) tap test and shunt treatment may vary due to the lack of a common protocol in INPH assessment. The present study aimed to assess whether a post-LP test amelioration of frontal cognitive dysfunctions, characterizing this syndrome, can differentiate INPH from similar neurological conditions and whether this improvement can predict INPH post–shunt outcomes.MethodSeventy-one consecutive patients referred for INPH suspicion and LP testing, were enrolled. According to the consensus guidelines criteria, 29 patients were diagnosed as INPH and 42 were assigned an alternative diagnosis (INPH-like group) after reviewing clinical, neuropsychological and imaging data, and before LP results. A comprehensive neuropsychological assessment for frontal executive, upper extremity fine motor functions, aphasias, apraxias, agnosias and gait evaluation were administered at baseline. Executive, fine motor functions and gait were re-examined post-LP test in all patients and post-shunt placement in INPH patients.ResultsOf the INPH patients, 86.2% showed cognitive amelioration in the post-LP test; in addition, all but one (97%) presented with neurocognitive and gait improvement post-shunt. Verbal phonological fluency and finger tapping task post-LP improvement predicted positive clinical outcome post-shunt. None of the INPH-like group presented with neurocognitive improvement post-LP.ConclusionsPost-LP amelioration of verbal fluency and finger tapping deficits can differentiate INPH from similar disorders and predict positive post-shunt clinical outcome in INPH. This becomes of great importance when gait assessment is difficult to perform in clinical practice.

Anaplastic Lymphoma Kinase in Glioblastoma: Detection/Diagnostic Methods and Therapeutic Options

BACKGROUND Glioblastoma (GBM) is the most aggressive and common brain tumor in adults, currently lacking effective life-prolonging and recurrence-preventing therapy; median survival of GBM patients stands at only 14-16 months. Increasing lines of evidence indicate that Anaplastic lymphoma kinase (ALK), a druggable tyrosine kinase receptor over-expressed in GBM, represents a potential therapeutic target in this tumor. OBJECTIVE An overview of the state of the art and the existing recent patents regarding potential exploitation of ALK as a therapeutic target and/or diagnostic/prognostic factor in GBM. METHOD Recent literature and patents focusing on or including ALK pre-clinical and clinical research in GBM have been identified and reviewed, and are discussed according to their potential use. RESULTS Numerous recent ALK-related patents were identified. They were reviewed/analyzed in relation to previously published research and categorized based on their potential in GBM: i) diagnosis/ prognosis, ii) drug-based therapeutic targeting of ALK using a single compound or combination schemes and iii) therapeutic ALK targeting by other means, e.g. ALK vaccination. CONCLUSION ALK targeting holds promise as a novel therapeutic approach in GBM, especially in combination schemes allowing multi-target therapy. Such schemes may incorporate detection-guided therapy and utilize next generation inhibitory compounds with improved central nervous system penetration. Moreover, identification of ALK-mediated molecular pathway(s) related to GBM carcinogenesis/ pathology and putative therapy resistance is of high priority and warrants further exploitation.

Epidemiology of first epileptic seizures in the northern Aegean island of Lesvos, Greece

We aimed at establishing the epidemiologic profile of first epileptic seizures (FES) in the Greek island of Lesvos. During a 1-year period (01/06/2010 to 31/05/2011), cases of FES admitted to the Lesvos General Hospital/addressed by general practitioners/private neurologists were prospectively identified. A total of 45 cases (30 males and 15 females; mean age ± SD of 59.4 ± 28.4 and 58.9 ± 26.8 years, respectively), were collected. The FES incidence rate was 52.1 (95% CI 37-67) per 105 persons. Provoked and unprovoked FES had an incidence of, 16.2 and 35.9 cases per 105 persons, respectively. Following age-adjustment to the 2000 US census population, incidence rates of FES (all types combined) were, 40.5 (95% CI 28-56) per 105 persons. Cerebrovascular disease (CVD) was the most prevalent etiologic factor. The present findings indicate a low-ranking incidence of FES in the studied population and highlight CVD as a leading causative factor.