Neurophysiological methods in headache diagnosis

Neurophysiological methods used in the diagnosis of headache, especially migraine are: electroencephalography (EEG), evoked cortical potentials (VEP, BAER, ERP), reflex responses, autonomic tests and transcranial magnetic stimulation (TMS). Interpretation of EEG can be important for the differential diagnosis of some disorders with headache as a presenting symptom. Noninvasiveness, accessibility and ability to repeat the test due to exposure to harmful ionization are the main advantages of EEG. The role of thorough medical history and clinical assessment in patients with headache should not be underestimated. Interictal EEG (between headache attacks) is not significant in routine evaluation of these patients, but can be useful in patients with unusual symptoms suggesting epilepsy or migraine. It is indicated in patients with an abrupt onset of headache, in patients with migraine followed by neurological signs, in basilar migraine, migraine with extended duration of aura and in cases where epilepsy is suspected. Headache as a symptom is present in various brain and systemic diseases and metabolic disorders. EEG changes seen in headache patients are not specific for a particular disorder, but can suggest additional evaluation and accelerate accurate diagnosis and earlier treatment. Visual evoked cortical potentials (VEP) and cognitive evoked potentials (ERP) in patients with migraine in interictal periods have shown differences in sensory processing between patients with headache and healthy controls. Neurophysiological methods (VEP, ERP) between migraine attacks show cortical hyperactivity and predisposition for further attacks. Brainstem auditory evoked responses (BAER) are a sensitive method for the detection of central nervous system damage. Activation of the brainstem during the migraine attack results in an amplitude increment seen soon after the end of the attack. According to recent studies, R2 component of the blink reflex was six times longer during migraine attack as compared to interictal values. This is thought to be a response to sensitization of the skin nociceptive afferent arch or other neurons in the trigeminal nucleus. In patients with cluster headache, autonomic tests generate cardiovascular and pupillary response suggesting systemic sympathetic hyperactivation connected to concurrent pupillary sympathetic hypofunction and modified opioid modulation. TMS is shown to be very useful for the detection of pathophysiological changes of numerous disorders including migraine, due to its excitatory and inhibitory effects. Recent studies have shown changes in motor and occipital cortex during TMS interictal excitability. Neurophysiological tests are used in differential diagnosis of headache, follow up of possible complications in patients with symptomatic headache as well as in neurorehabilitation. In addition, electrophysiological diagnostic test can contribute to better understand the headache pathophysiology.     

Association of epilepsy and headache from the patient perspective

Headache occurs more frequently in patients with epilepsy as compared to the general population. Current studies in patients with epilepsy and migraine show that this increased frequency is independent of the seizure type, etiology or age at onset. People with epilepsy are 2.4 times more likely to be diagnosed with migraine. In our study, we evaluated patients' attitudes toward comorbidity of epilepsy and all headache types. Study results showed a significant number of patients to have experienced headaches after being diagnosed with epilepsy, and some of them assumed it was a side effect of their antiepileptic drug. Based on these data, we propose a more detailed assessment of the history of epilepsy including questions on headache, and offer the epilepsy patient a newer antiepileptic drug. In this way, we can significantly decrease the comorbidity of these two neurologic disorders and improve the quality of life in epilepsy patients.     

Malignant blue nevus with lymph node metastases in five-year-old girl

We report an unusual case of a malignant blue nevus in a five-year-old girl, which turned out to be malignant only after the development of lymph node metastases three years after the excision of the primary tumor on the patient's cheek. A functional bilateral neck dissection was performed and the patient is alive with no evidence of disease 8 years after the excision of the primary skin lesion.     

Different GABAA receptor subtypes mediate the anxiolytic, abuse-related, and motor effects of benzodiazepine-like drugs in primates

Benzodiazepines exert their effects by binding to multiple subtypes of the GABAA receptor, the predominant subtypes in the brain being those that contain alpha1-, alpha2-, alpha3-, and alpha5-subunits. To understand the potentially different roles of these subtypes in the therapeutic and side effects of benzodiazepines, we evaluated GABAA receptor subtype-preferring compounds in nonhuman primate models predictive of anxiolytic, sedative, motor, subjective, and reinforcing effects of benzodiazepine-type drugs. These compounds included zolpidem, which shows preferential binding to GABAA receptors containing alpha1-subunits (alpha1GABAA receptors); L-838,417, which shows functional selectivity for alpha2GABAA, alpha3GABAA, and alpha5GABAA receptors; and nonselective conventional benzodiazepines. The results provide evidence in nonhuman primates that alpha1GABAA receptors do not play a key role in the anxiolytic and muscle-relaxant properties of benzodiazepine-type drugs; instead, these effects involve alpha2GABAA, alpha3GABAA, and/or alpha5GABAA subtypes. Our results also suggest that the alpha1GABAA receptor subtype might be critically involved in the subjective, sedative, and motor effects of benzodiazepine-type drugs. In contrast, stimulation of alpha1GABAA receptors is sufficient, but not necessary, for mediation of the abuse potential of these drugs.     

Prognostic factors in anaplastic carcinoma of the thyroid—a multivariate survival analysis of 188 patients

Background Multivariate studies concerning the prognosis of patients with anaplastic carcinoma of the thyroid gland are scarce. The aim of our study was to determine the prognostic factors associated with survival of patients with anaplastic carcinoma in Slovenia, an iodine-deficient region.Methods This retrospective study was carried out on a group of 188 patients (130 female, 58 male; median age 68 years) with anaplastic carcinoma of the thyroid who had been treated at a tertiary care centre from 1972 to 2003. For each patient, data on gender, age, disease history, extent of disease, morphological characteristics, mode of therapy, and survival were collected. Statistical correlation between possible prognostic factors and survival was analysed by univariate and Coxs multivariate analysis. Treatment modality was not included in the analysis to avoid selection bias.Results The median survival of all the patients was 3 (±0.36) months. Overall 1-year survival of our patients was 13%, and 2-year survival was 6%. Multivariate analysis showed that the patients age, performance status, tumour growth, tumour extension and distant metastases were independent prognostic factors for the survival.Conclusion Patients younger than 71 years, with a good performance status and slowly growing tumours confined to the thyroid, and without distant metastases, had the best prognosis.This paper is a part of research study J3-6092-0302-04, supported by the Ministry of Education, Science and Sport of Slovenia. The work was presented, in part, at the first European Society of Endocrine Surgery (ESES), Pisa, Italy, 13–15 May 2004     

Apoptotic pathways in ovarian surface epithelium of human embryos during embryogenesis and carcinogenesis: Close relationship of developmental plasticity and neoplasm

Cell differentiation and different pathways of cell death were immunohistochemically analyzed in ovaries of six human embryos, 20 serous borderline tumors (SBT) and ovarian serous carcinomas (OSC) using markers for apoptosis (caspase-3, AIF, TUNEL) and stemness (Oct-4). In the 5–8-week ovaries, caspase-3 was absent in the ovarian surface epithelium (ose) and mildly positive in the ovarian stroma (os), AIF was expressed moderately, while Oct-4 expression gradually decreased during that period. Some ovarian cells expressed only caspase-3 or AIF together with TUNEL, while both caspase-3 and AIF were co-expressed in other ovarian cells. Mild expression of Oct-4 and caspase-3 characterized some cells of SBT, while their expression varied from mild to strong in OSC. AIF displayed mild to strong expression in ose of SBT and moderate to strong expression in OSC, while no expression of AIF was observed in os of both tumors. In the ose of both SBT and OSC, caspase-3 and AIF were co-expressed only occasionally, while AIF and Oct-4 were co-expressed strongly. Our study showed the presence of stemness cells and different pathways of cell death (caspase-3 and AIF-mediated) in the ovarian tissue during development and carcinogenesis, indicating the correlation between developmental plasticity in human embryonic ovaries and OSC.     

The pathogenic potential of different pulsed-field gel electrophoresis types of Listeria monocytogenes strains isolated from food in Northeast Bosnia and Herzegovina

Listeria monocytogenes is often present in meat and meat products that are sold in the area of northeast Bosnia and Herzegovina. The major objective of this study was to examine the virulence of L. monocytogenes strains isolated from these types of food in that geographic area. Polymerase chain reaction was used to detect eight genes responsible for virulence of this pathogen, namely, prfA, inlA, inlB, hly, plcA, plcB, actA, and mpl. All examined isolates were confirmed to possess the eight virulence genes. Ten different pulsed-field gel electrophoresis (PFGE) macrorestriction profiles were recognized among 19 L. monocytogenes strains after restriction with two different endonucleases (ApaI and AscI). The pathogenicity of three different PFGE types of L. monocytogenes was confirmed through in vivo tests, which were performed on female white mice (Pasteur strain), and it ranged from 3.55 × 10(8) LD50 to 1.58 × 10(10) LD50. All of the three different PFGE types of L. monocytogenes were regarded as moderately virulent in relation to the reference strain L. monocytogenes Scott A. This result might be one of the reasons for the absence of reported listeriosis in northeast Bosnia and Herzegovina, despite the high degree of food contamination with this pathogen.     

Genetics of Mechanosensation in the Heart

Mechanosensation (the ultimate conversion of a mechanical stimulus into a biochemical signal) as well as mechanotransduction (transmission of mechanically induced signals) belong to the most fundamental processes in biology. These effects, because of their dynamic nature, are particularly important for the cardiovascular system. Therefore, it is not surprising that defects in cardiac mechanosensation, are associated with various types of cardiomyopathy and heart failure. However, our current knowledge regarding the genetic basis of impaired mechanosensation in the cardiovascular system is beginning to shed light on this subject and is at the centre of this brief review.