SPECT and TCD studies in cluster headache patients.

We investigated regional cerebral blood flow (rCBF) with Tc99m-HMPAO single photon emission computed tomography (SPECT) and blood flow velocity in the middle cerebral artery (MCA) with transcranial Doppler (TCD) ultrasound. Nineteen cluster headache patients participated in the study, 9 of them underwent both examinations, whereas in 6 patients only SPECT and in 4 patients only TCD was performed. Patients were examined during spontaneous and/or provoked attacks and when symptom-free in a cluster period. Six patients showed moderate frontal hyperperfusion, 2 had frontal hypoperfusion whereas no change from headache-free rCBF occurred in 7 patients. Statistical analysis of MCA velocities in 13 patients showed a significant decrease in the mean flow velocity compared with the headache-free values on the symptomatic side. Our findings suggest that the alteration of cerebral circulation during cluster attacks might be of secondary nature.

Medicinal chemistry of antimigraine drugs.

Migraine is one of the most frequent neurological disorder with high impact on the quality of life. Primary headaches such as migraine are pathophysiologically complex disorders. The concept of the trigeminovascular system dysfunction in migraine has led to a number of drug discoveries dramatically changing the treatment options. Acute and prophylactic therapy targeting either the trigeminovascular system or central structures involve several groups of drugs with peculiar medicinal chemistry. In the proposed review up to date concept of treatment strategy, medicinal chemistry data of the drugs used will be summarized. The present review gives detailed information on drugs effective in aborting migraine attacks (by inhibiting prostanoid synthesis, are agonists of serotonin 5-HT1B/D receptors, on the recently introduced CGRP-receptor antagonists) and the drugs recommended for prophylactic treatment (selected beta-adrenergic receptor antagonists, Ca-channel inhibitors, antiepileptics, antidepressants). The pharmacokinetics, fate in the body (absorption, distribution, metabolism, excretion) and significant pharmacological effects as well as the recent bioanalytical methods for their determination are presented.

Cluster headache patients show marked intensity dependence of cortical auditory evoked potentials during and outside the bout.

Central serotonergic neurotransmission was assessed using intensity dependence of cortical auditory evoked potentials (IDAP) in cluster headache (CH) patients during both the active and interictal period. In 15 episodic CH patients and 13 controls previously described methods were used and amplitude-stimulus intensity function (ASF) slopes were computed. In the cluster group mean ASF slope was significantly steeper than in the control group both during the active period (1.53+/-0.90 vs. 0.77+/-0.85, P=0031) and interictally (1.85+/-1.20 vs. 0.77+/-0.85, P=0012). In the cluster group IDAPs of active and interictal period did not differ significantly (P=0378). Duration of the disease or the present bout, distance from the last attack did not correlate with ASF slopes. In conclusion, our results are compatible with decreased level of serotonergic neurotransmission in raphe-cortical pathways. Diminished serotonergic activity in raphe-hypothalamic serotonergic pathways might be hypothesized influencing the activity of hypothalamic neurons and thus play a role in the genesis of cluster headache.

Plasma nociceptin levels are reduced in migraine without aura.

It was demonstrated that both nociceptin, a novel opioid neuropeptide, and its receptor are present in trigeminovascular neurons. In an animal model nociceptin dose-dependently inhibited neurogenic dural vasodilatation. These results suggest that nociceptin may be involved in neurovascular headaches such as migraine. To test this hypothesis, we studied circulating nociceptin levels in 18 patients suffering from migraine without aura and in 24 controls. Headache-free migraineurs had significantly lower nociceptin levels than controls (5.79 +/- 1.82 vs. 9.74 +/- 2.43 pg/ml, P < 0.0001, Student's t-tests). Nociceptin levels were further reduced in six patients studied in the first 3 h of typical migraine attacks (1.04 +/- 0.17 pg/ml). Nociceptin levels correlated with the frequency of attacks in this group of migraineurs. Lower interictal nociceptin levels may contribute to a defective regulation of trigeminovascular neurons in migraineurs which might be important in the pain process of migraine.

Circulating nociceptin levels during the cluster headache period.

The trigeminal innervation of the dura and its vessels has a prominent role in the mechanism of cluster headache. Nociceptin, an opioid neuropeptide, is the endogenous ligand of the OP-4 receptor, with both algesic and analgesic properties depending on the site of action. Nociceptin and its receptor are expressed by trigeminal ganglion cells where they co-localize with calcitonin gene-related peptide, a marker peptide of the trigeminovascular neurones. Nociceptin inhibits neurogenic dural vasodilatation, a phenomenon related to trigeminovascular activation. To explore its possible involvement in cluster headache, we studied circulating levels of nociceptin when attack-free during the cluster period, and also after the termination of the cluster period, using radioimmunoassay. In 14 cluster headache patients nociceptin levels during the cluster period were significantly lower than in age-, and sex-matched controls (4.91 +/- 1.96 vs. 9.58 +/- 2.57 pg/ml, P < 0.01). After the termination of the cluster period nociceptin levels (8.60 +/- 1.47 pg/ml) were not statistically different from controls. Nociceptin levels did not correlate with age, length of disease or episode length. Lower nociceptin levels during the cluster period may result in a defective regulation of trigeminal activity that might not protect sufficiently against the attacks.

Health-related and condition-specific quality of life in episodic cluster headache.

Health-related quality of life was studied in 35 episodic cluster headache (CH) patients during and after the cluster period, using a generic (SF-36) and a headache-specific (MSQ2.1) instrument. The results were compared with those of age- and sex-matched migraineurs (n = 53) and healthy persons (n = 62). During the cluster period patients had lower scores than controls in all SF-36 and MSQ2.1 domains. The difference was significant for most SF-36 and all MSQ2.1 domains. Although CH patients had lower scores than migraineurs on most scales, the difference was significant only on SF-36 scores measuring bodily pain and social functioning. There was a good correlation between the two instruments. After the termination of the cluster period the quality of life of patients was similar to that of headache-free controls. Generic and headache-specific QoL are severely impaired in CH and this impairment is at least as severe as in migraine.

Postgraduate education in neurology in Central and Eastern Europe.

The policy of the European co-operation in the new atmosphere of an international solidarity became one of the priorities of the European Federation of Neurological Societies (EFNS). It could be hardly pursued more efficiently in any other field of neurological performance as in education. To review several aspects of neurological practice and education the 'First European Co-operation Neurology Workshop' was held in the castle of Trest', Czech Republic, 13-20 April 2000. Participants from 15 countries (Albania, Belarus, Bulgaria, Croatia, Czech Republic, Estonia, Georgia, Hungary, Moldova, Poland, Romania, Russia, Slovak Republic and Slovenia), covering a region of 316 million inhabitants and 25 000 neurologists, presented their national postgraduate education systems (besides other topics). We refer data on density of medical doctors and that of neurologists, pre-board certification phase, board examination, continuing medical education (CME), and qualification rewards. Illustrative data were put in the comparative tables. This first meeting has founded the basis for a dynamic future collaboration in order to continue the integration process and an exchange of current information regarding CME amongst central and eastern countries as well as western Europe.

Inherited prion disease with A117V mutation of the prion protein gene: a novel Hungarian family.

Three members of a family with inherited prion disease are reported. One additional family member had a progressive neurological disease without details. Two developed symptoms of ataxia, dementia, myoclonus, rigidity, and hemiparesis, and one had a different phenotype with the combination of lower motor neuron deficit, parkinsonism, intellectual decline, and ataxia. In this last patient cell loss of the anterior horn motor neurons and chronic neurogenic muscle atrophy was evident. Immunostaining for the prion protein disclosed unicentric and multicentric plaques, and coarse and fine granular positivity. Genetic analysis of the prion protein gene of the propositus showed a 117 codon alanine to valine mutation and homozygous 129 valine/valine genotype.