Toomas Asser

Seizure Disorders in Patients with Brain Tumors

The aim of this study was to analyze the clinical data of patients with epileptic seizures and diagnosed brain tumors. Analysis included 711 patients with primary and secondary brain tumors. 165 (23%) patients had experienced at least one seizure before tumor diagnosis. The mean time from the first epileptic seizure to tumor diagnosis was 16 months. The patient’s age, location and pathology of tumor were associated with occurrence of seizures. Seizures were more common in patients aged 30–50 years. Tumors involving the frontal, frontoparietal, temporal and frontotemporal lobes were associated with occurrence of seizures. According to the histological diagnosis, patients with mixed gliomas (62%), oligodendrogliomas (53%) and astrocytomas (42%) experienced seizures most frequently.

Irreversible motor impairment in young addicts--ephedrone, manganism or both?

Background –  Parkinsonian syndrome related to intravenous use of a ‘designer’ psychostimulant, derived from pseudoephedrine using potassium permanganate as the oxidant, has been observed in drug addicts in Estonia.

The BRAIN TRIAL: a randomised, placebo controlled trial of a Bradykinin B2 receptor antagonist (Anatibant) in patients with traumatic brain injury

BackgroundCerebral oedema is associated with significant neurological damage in patients with traumatic brain injury. Bradykinin is an inflammatory mediator that may contribute to cerebral oedema by increasing the permeability of the blood-brain barrier. We evaluated the safety and effectiveness of the non-peptide bradykinin B2 receptor antagonist Anatibant in the treatment of patients with traumatic brain injury. During the course of the trial, funding was withdrawn by the sponsor.MethodsAdults with traumatic brain injury and a Glasgow Coma Scale score of 12 or less, who had a CT scan showing an intracranial abnormality consistent with trauma, and were within eight hours of their injury were randomly allocated to low, medium or high dose Anatibant or to placebo. Outcomes were Serious Adverse Events (SAE), mortality 15 days following injury and in-hospital morbidity assessed by the Glasgow Coma Scale (GCS), the Disability Rating Scale (DRS) and a modified version of the Oxford Handicap Scale (HIREOS).Results228 patients out of a planned sample size of 400 patients were randomised. The risk of experiencing one or more SAEs was 26.4% (43/163) in the combined Anatibant treated group, compared to 19.3% (11/57) in the placebo group (relative risk = 1.37; 95% CI 0·76 to 2·46). All cause mortality in the Anatibant treated group was 19% and in the placebo group 15.8% (relative risk 1.20, 95% CI 0.61 to 2.36). The mean GCS at discharge was 12.48 in the Anatibant treated group and 13.0 in the placebo group. Mean DRS was 11.18 Anatibant versus 9.73 placebo, and mean HIREOS was 3.94 Anatibant versus 3.54 placebo. The differences between the mean levels for GCS, DRS and HIREOS in the Anatibant and placebo groups, when adjusted for baseline GCS, showed a non-significant trend for worse outcomes in all three measures.ConclusionThis trial did not reach the planned sample size of 400 patients and consequently, the study power to detect an increase in the risk of serious adverse events was reduced. This trial provides no reliable evidence of benefit or harm and a larger trial would be needed to establish safety and effectiveness.Trial RegistrationThis study is registered as an International Standard Randomised Controlled Trial, number ISRCTN23625128.

Epidemiology of Primary Central Nervous System Tumors in Estonia

During the period from 1986 to 1996, 1,665 cases of primary central nervous system (CNS) tumors were identified in the resident population of Estonia. Histological verification was available in 81% of the cases. Gliomas were more common in men, while meningiomas and neurinomas were more common in women. No significant difference was observed between the sexes for all primary CNS tumors. The age-specific incidence increased from the age of 30, reached a maximum in the age range of 50–69 years and declined in the elderly which may reflect under-diagnosis. The age-adjusted incidence rate for CNS tumors was 8.5/100,000 population. A comparison of our results with those of a previous study carried out in Estonia revealed a significant histology-specific increase in incidence in all age groups.

Prevalence of Parkinson's disease in Estonia.

Taba P, Asser T. Prevalence of Parkinsons disease in Estonia.

Changes in viscoelastic properties of skeletal muscles induced by subthalamic stimulation in patients with Parkinson's disease

BACKGROUND Objective measurements would be useful to document the effect of deep brain stimulation in alleviating rigidity in patients with Parkinsons disease. The aim of the study was to examine the changes of viscoelastic properties in skeletal muscles as indicators of rigidity. METHODS Six patients in an advanced stage of Parkinsons disease participated in the study. The study took place in the off-medication conditions after one night of drug withdrawal. The wrist rigidity was examined according to the Unified Parkinsons Disease Rating Scale in both sides. Myotonometry (Myoton) was used to determine stiffness and elasticity in extensor digitorum muscles bilaterally. The measurements were repeated and compared during the stimulation-on and stimulation-off periods. FINDINGS A comparison of mean clinical motor scores revealed a significant improvement of parkinsonian symptoms due to brain stimulation. In particular, arm rigidity improved on average from 2.83 (1-4) in stimulation-off phase to 1.17 (0-2) in stimulation-on phase (P<0.05). The mean values of elasticity and stiffness were not significantly different in stimulation-on and stimulation-off conditions. The patients with elevated clinical rigidity scores had higher mean values of stiffness (262.5 vs 211.0; P<0.05) but the differences in elasticity were not significant. INTERPRETATION Increased rigidity is associated with increased values of viscoelastic stiffness. This paper supports the use of myotonometry for objective quantification of rigidity and in the future, this tool could prove helpful for optimizing deep brain stimulation settings in patients with Parkinsons disease.

Tenascin expression patterns and cells of monocyte lineage: relationship in human gliomas.

Stromal extracellular matrix (ECM) components are thought to play an important role in regulating invasion of human gliomas. Macrophages and microglial cells may heavily influence the integrity of the extracellular compartment of gliomas, and the affected ECM may play a key role in regulating migratory activity of both tumor cells and macrophages/microglia. The aim of this investigation was to study immunohistochemically the expression patterns of four ECM components: fibronectin, laminin, collagen IV, and tenascin (TN) in human gliomas, with special attention to TN. Our main goal was to study the possible correlation between TN expression and macrophagic/microglial infiltration in gliomas. Altogether, 90 gliomas were studied. Tumors included 46 glioblastomas, 19 anaplastic gliomas, 22 low grade gliomas, and 3 pilocytic astrocytomas. Vascular TN prevailed in perinecrotic areas of glioblastomas, whereas interstitial TN was more often expressed distant from necrosis and in the ECM of anaplastic and low grade gliomas. Double staining with CD68 and anti-TN antibodies showed that macrophagic/microglial density was significantly higher in TN-positive areas of most of the glioblastomas and anaplastic gliomas, whereas microglial percentage from total number of CD68-positive cells was in most of the cases significantly higher in TN-negative areas. In addition, we saw a morphologically spatial correlation between higher densities of macrophagic/microglial infiltration and TN expression in perinecrotic areas in glioblastomas. Attachment of macrophages to TN-positive basement membrane zones of newly formed stromal blood vessels was evident. On the basis of our results, we conclude that TN may play a crucial role in regulating trafficking of cells of monocyte lineage in human gliomas.

Impact of PARP-1 and DNA-PK expression on survival in patients with glioblastoma multiforme.

PURPOSE To analyze, whether higher tumor levels of DNA repair enzymes contribute to worse treatment results of glioblastoma multiforme (GBM) patients after postoperative radiotherapy. MATERIALS AND METHODS Thirty four patients with GBM received postoperative radiotherapy. Tumor sections were examined for poly-ADP ribose polymerase-1 (PARP-1) and DNA protein kinase (DNA-PK) expression. Immunohistochemical staining intensities of PARP-1 and DNA-PK were determined (score 0-3) and expression levels were correlated with patients overall survival. RESULTS Median survival time of the whole study group was 10.0 months (95% CI 8.1-11.9). Median survival of patients with high and low (≥median and <median) tumor PARP-1 levels were 10.0 months (95% CI 7.9-12.1) and 12.0 months (95% CI 8.3-15.7), respectively (p=0.93). In contrast, median survival of patients with high and low tumor DNA-PK levels were 9.0 months (95% CI 7.2-10.8) and 13.0 months (95% CI 10.7-15.3), respectively (p=0.02). In multivariate analysis, DNA-PK expression emerged as a significant independent predictor for overall survival (HR 3.9, 95% CI 1.5-10.7, p=0.01). CONCLUSION This hypothesis generating study showed that high tumor levels of DNA-PK correlate with poor survival of GBM patients. Further studies are needed to confirm these results and to clarify whether DNA-PK inhibitors might have a potential to radiosensitize GBM and improve the treatment outcome of this devastating disease.

The Possible Role of CSF Hydrodynamic Parameters Following in Management of SAH Patients

It is suggested that reduced intracranial compliance may be present even when measured ICP is normal and may precede clinical deterioration. Our findings reflect a decompensation of hydrodynamic parameters more pronounced 4-7 postictal days, when compliance is reduced not only in patients with poor clinical condition, but also in patients with Hunt-Hess grade I-III. Increased CSF outflow resistance in the first few days is not surprising; it is thought to be due to the blockage of flow of CSF through the basal subarachnoid cisterns and clogging of the arachnoid villi with erythrocytes and fibrin. Enlargement of ventricles seen on CT scan at the same time suggests the development of acute hydrocephalus. During the first days after SAH, our data reflects evidence of ventricular enlargement in patients presenting with both poor and better clinical condition. We conclude that the monitoring of ICP and dynamic measuring of CSF hydrodynamic parameters is important for longer than the generally accepted few days for selected cases after SAH.

Alterations in opioid system of the rat brain after cat odor exposure

The effect of cat odor exposure was studied on morphine-induced increase of exploratory behavior and on the expression of opioid genes in forebrain structures of male Wistar rats. Treatment with morphine (1 mg/kg) induced a significant increase in exploratory behavior in an unfamiliar environment in rats. Previous exposure of animals to cat odor completely abolished this stimulating action of mu-opioid receptor agonist on exploratory activity. Cat odor exposure induced a significant increase in the expression of pro-opio-melanocortin (POMC) and mu-opioid receptor (MOR) genes in the brain structures related to anxiety and motivation. This study clearly demonstrates that cat odor exposure increases the activity of opioid system in rat forebrain structures.