Malgorzata Kolodziej

Percutaneous minimally invasive fetoscopic surgery for spina bifida aperta. Part III: neurosurgical intervention in the first postnatal year

To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA).

Percutaneous minimally‐invasive fetoscopic surgery for spina bifida aperta ‐ Part III ‐ Postnatal neurosurgical interventions in the first year of life

To evaluate the need for postnatal neurosurgical intervention after fetoscopic patch coverage of spina bifida aperta (SBA).

Glycobiology in malignant gliomas: expression and functions of galectins and possible therapeutic options.

Malignant gliomas, the most common malignant primary brain tumors, have a deleterious clinical prognosis of approximately 12 months in unselected series. The resistance against antineoplastic therapy is apparently not only associated with a high proliferative potential, marked antiapoptotic resistance and high migratory capacity. Effective mechanisms to escape the immune response of the organism and an intense neoangiogenesis also contribute to the aggressive growth of these neoplasms. In addition to a number of molecular mechanisms, the group of glycohydrate-binding galectins seems to contribute to the aggressive growth of malignant gliomas. Galectin-1, -3, -4 and -8 have been shown to be overexpressed in malignant gliomas. Galectin-1 is known to be involved in glioma cell migration and possibly also in proliferation. In this review, various aspects of glioma biology and their therapeutic relevance is discussed. The role of galectins in apoptosis-resistance, immune response and angiogenesis is discussed and explained why these molecules are interesting targets of glioma therapy.

Cerebrospinal fluid ferritin — Unspecific and unsuitable for disease monitoring

BACKGROUND AND PURPOSE Subarachnoid hemorrhage is sometimes difficult to diagnose radiologically. Cerebrospinal fluid (CSF) ferritin has been proposed to be highly specific and sensitive to detect hemorrhagic central nervous system (CNS) disease. We analyzed here the specificity of CSF ferritin in a large series of various CNS diseases and the influence of serum ferritin. MATERIALS AND METHODS CSF ferritin, lactate, protein and total cell count were analyzed in 141 samples: neoplastic meningitis (n=62), subarachnoid hemorrhage (n=20), pyogenic infection (n=10), viral infection (n=10), multiple sclerosis (n=10), borreliosis (n=5) and normal controls (n=24). Cerebrospinal fluid ferritin was measured with a microparticle immunoassay. In addition, serum and CSF ferritin were compared in 18 samples of bacterial and neoplastic meningitis. RESULTS In CNS hemorrhage, median ferritin was 51.55μg/L (sensitivity: 90%) after the second lumbar puncture. In neoplastic meningitis, the median CSF ferritin was 16.3μg/L (sensitivity: 45%). Interestingly, ferritin was higher in solid tumors than that in hematological neoplasms. In 90% of pyogenic inflammation, ferritin was elevated with a median of 53.35μg/L, while only 50% of patients with viral infection had elevated CSF ferritin. In ventricular CSF, median ferritin was 163μg/L, but only 20.6μg/L in lumbar CSF. Ferritin was normal in multiple sclerosis and borreliosis. CONCLUSIONS Ferritin was elevated not only in hemorrhagic disease, but also in neoplastic and infectious meningitis. Ferritin was not a reliable marker of the course of disease. The influence of serum ferritin on CSF ferritin is negligible. We conclude that elevated CSF ferritin reliably, but unspecifically indicates severe CNS disease.

Chudley–McCullough Syndrome: Variable Clinical Picture in Twins with a Novel GPSM2 Mutation

Chudley-McCullough syndrome (CMS) is a rare autosomal recessive disorder characterized by sensorineural deafness, agenesis of the corpus callosum, frontal polymicrogyria, interhemispheric cyst, and ventricular enlargement. CMS is caused by mutations in the GPSM2 gene, but until now no more than eight different mutations are on record. We describe two dizygotic twins with a novel homozygous loss-of-function mutation (c.1093C > T; p.Arg365*). While one child developed hydrocephalus-prompting shunt implantation immediately after birth, the other sibling did not. The combination of sensorineural hearing loss and partial agenesis of the corpus callosum is a highly recognizable clinico-radiological entity that should prompt mutational analysis of the GPSM2 gene.

Defining Prolonged Length of Acute Care Stay for Surgically and Conservatively Treated Patients with Spontaneous Intracerebral Hemorrhage: A Population-Based Analysis.

Background. The definition of prolonged length of stay (LOS) during acute care remains unclear among surgically and conservatively treated patients with intracerebral hemorrhage (ICH). Methods. Using a population-based quality assessment registry, we calculated change points in LOS for surgically and conservatively treated patients with ICH. The influence of comorbidities, baseline characteristics at admission, and in-hospital complications on prolonged LOS was evaluated in a multivariate model. Results. Overall, 13272 patients with ICH were included in the analysis. Surgical therapy of the hematoma was documented in 1405 (10.6%) patients. Change points for LOS were 22 days (CI: 8, 22; CL 98%) for surgically treated patients and 16 days (CI: 16, 16; CL: 99%) for conservatively treated patients. Ventilation therapy was related to prolonged LOS in surgically (OR: 2.2, 95% CI: 1.5–3.1; P < 0.001) and conservatively treated patients (OR: 2.5, 95% CI: 2.2–2.9; P < 0.001). Two or more in-hospital complications in surgical patients (OR: 2.7, 95% CI: 2.1–3.5) and ≥1 in conservative patients (OR: 3.0, 95% CI: 2.7–3.3) were predictors of prolonged LOS. Conclusion. The definition of prolonged LOS after ICH could be useful for several aspects of quality management and research. Preventing in-hospital complications could decrease the number of patients with prolonged LOS.

Subcutaneous Peripheral Nerve Field Stimulation for the Treatment of Chronic Back Pain: Patient Selection and Technical Aspects.

A wide variety of therapeutic options are available for the treatment of chronic back pain, a very common condition in Western countries with high related social and economic costs. Nevertheless, it is not always possible to achieve adequate long-term pain relief in spite of intensive analgesic therapies. Subcutaneous peripheral nerve field stimulation (sPNFS) is a newly approved neuromodulative treatment for back pain. In previously reported case series, it has provided encouraging results on long-term pain relief, improvement in quality of life, and a reduced need for analgesic drugs. Although the surgical technique is simple, there is neither consensus for patient management nor a standardized procedure for the implantation procedure. After consideration of our personal experience and the published literature, a basic recommendation has now been developed. This represents the first step toward planning prospective studies and standardization of this treatment and will permit comparison of this technique and the results with sPNFS.

Neuronal Fractal Dynamics

Synapse formation is a unique biological phenomenon. The molecular biological perspective of this phenomenon is different from the fractal geometrical one. However, those perspectives are not mutually exclusive and supplement each other. A cornerstone of the first one is a chain of biochemical reactions with the Markov property, that is, a deterministic, conditional, memoryless process ordered in time and in space, in which the consecutive stages are determined by expression of some regulatory proteins. The coordination of molecular and cellular events leading to the synapse formation occurs in fractal time-space, that is, the time-space that is not only the arena of events but also influences those events actively. That time-space emerges owing to coupling of time and space through nonlinear dynamics. The process of synapse formation possesses fractal dynamics with non-Gaussian distribution of probability and a reduced number of molecular Markov chains ready for transfer of biologically relevant information.

High-mobility group AT-hook protein 2 expression and its prognostic significance in MGMT methylated and unmethylated glioblastoma

High-mobility group AT-hook protein 2 (HMGA 2) is a transcription factor associated with malignancy and poor prognosis in a variety of human cancers. We correlated HMGA 2 expression with clinical parameters, survival, and O-6-methylguanine-DNA methyltransferase methylation status (MGMT) in glioblastoma patients. HMGA 2 expression was determined by performing quantitative real-time polymerase chain reaction (qPCR) and immunohistochemistry (IHC) in 44 glioblastoma patients and 5 non-tumorous brain specimens as controls. Gene expression levels of MGMT methylated vs. unmethylated patients, and gene expression levels between patient groups, both for qPCR and IHC data were compared using the Mann-Whitney U test. The relationship between HMGA 2 expression, progression-free survival and overall survival was analyzed using the Kaplan-Meier method and the log-rank test. P-values of <0.05 were considered statistically significant throughout the analyses. The mean age of patients at diagnosis was 57.4 ± 15.7 years, and the median survival was 16 months (SE 2.8; 95% CI, 10.6-21.4). HMGA 2 gene expression was significantly higher in glioblastoma compared to normal brain tissue on qPCR (mean, 0.35; SD, 0.27 vs. 0.03, SD, 0.05) and IHC levels (IRS mean, 17.21; SD, 7.43 vs. 3.20; SD, 1.68) (p=0.001). Survival analysis revealed that HMGA 2 overexpression was associated with a shorter progression-free and overall survival time in patients with methylation (n=24). The present study shows a tendency that HMGA 2 overexpression correlates with a poor prognosis of glioblastoma patients independent of MGMT methylation status. The results suggest that HMGA 2 could play an important role in the treatment of glioblastoma and could have a function in prognosis of this type of cancer.