Utilization of acute vascular imaging and neurointervention for acute ischaemic stroke patients in 20 Hungarian stroke centers.

BACKGROUND AND PURPOSE: Acute mortality rate of stroke in Hungary is significantly higher than in Western Europe, which is likely to be partially attributable to suboptimal treatment. METHODS: We examined the use of acute vascular imaging and mechanical thrombectomy for acute ischaemic stroke patients. We collected data on 20 consecutive patients from Hungarian stroke centers before 31st August 2016. RESULTS: Out of the reported 410 patients, 166 (40.4%) underwent CT angiography and 44 (10.7%) had mechanical thrombectomy. CONCLUSION: Only about 1/3 of acute ischaemic stroke patients eligible for thrombectomy actually had it. The underlying reasons include long onset-to-door time, low utilization of acute vessel imaging and a limited neuro-intervention capacity needing improvement.

Current status of epilepsy health care for adult patients from central and eastern European Union countries--a survey of members of the Central Europe Epilepsy Experts Working Group.

PURPOSE: The aim of this survey was to review and compare the current approaches to epilepsy management in central and eastern EU (CEEU) countries. METHOD: The questionnaire was sent to ten invited experts from Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. It focused on the treatment of adults. RESULTS: The number of neurologists and epilepsy reference centers is highly variable in CEEU countries. None of the analyzed states has a formal specialization in epileptology. No universal state-approved criteria for reference centers exist in Czech Republic, Estonia, Hungary, Latvia, and Slovenia. Generally, the protocols for epilepsy treatment in CEEU countries, including drug-resistant epilepsy, are in accordance with international guidelines; however, most countries have their own national standards of care and some have local clinical guidelines. Also, the reimbursement systems for antiepileptic drugs in CEEU countries are highly variable. Seven countries have epilepsy surgery centers. The costs of epilepsy surgeries are fully reimbursed, procedures performed abroad may also be covered. The length of time spent on waiting lists for surgery following the completion of preoperative investigations varies from two weeks to three years. The fraction of patients who qualified and were operated on within 12 months ranges from 20% to 100%. CONCLUSION: The lack of unified procedures pertaining to the evaluation and therapy of epilepsy is reflected by marked differences in access to treatment modalities for patients from CEEU countries.

[New antiepileptic drugs, and therapeutic considerations]. / Uj antikonvulzív szerek es terápiás szempontok.

Epilepsy is not a singular disease, but a variety of disorders. It affects up to 0.5% of the population. Over the past decade, researchers have made great advances in the field of epilepsy. These have been accompanied by the licensing of a great number of antiepileptic drugs. However, despite these efforts, up to 15-20% of patients have refractory epilepsy. The novel antiepileptic drugs must suit several requirements: higher efficacy, especially in resistant cases, better tolerability, and improved pharmacokinetic properties. Recently, three new drugs have been introduced to the market. Retigabine is a carbamic derivate, and its anticonvulsive properties are largely due to its ability to prolong the opening of neuronal voltage-gated potassium Kv7.2 and Kv7.3 channels. Lacosamide is a functionalized amino acid, and selectively enhances voltage-gated sodium channel slow inactivation. Eslicarbazepine acetate is a new member of the dibenzazepine family, and blocks the fast inactivated voltage-gated sodium channel. All three of them differ from the foregoing agents in several important ways, including new mechanism of action (retigabine, lacosamide), or pharmacokinetics (eslicarbazepine acetate). These novel anticonvulsants appear to be a safe and effective addition to the armamentarium for the treatment of patients with refractory epilepsy. However, it will take the consideration of new concepts in shaping the new therapeutic algorithm.

[Botulinum toxin therapy for focal dystonia]. / A fokális dystoniák kezelése botulinum toxinnal.

UNLABELLED: Dystonia is a syndrome characterized by sustained muscle contraction. It is frequently causing twisting and repetitive movements, or leading to development abnormal postures. The management of the disease is usually consists of medication, surgical interventions, botulinum toxin injection, or other complementary methods. The authors have been using the botulinum toxin treatment since 1991. AIM: The goal of the study was to investigate the efficacy and safety of the botulinum toxin injection, in patients with focal dystonia and hemifacial spasm. METHODS: A total of 94 patients diagnosed with cervical dystonia (n=33), blepharospasm (n=32), or hemifacial spasm (n=29) were treated. The mean age of the patients was 62.4 years, and the mean duration of the therapy was 6.8 years. The medication took place with local injection of botulinum toxin type A. The efficacy of the treatment was assessed with Patient Global Impression scale. The authors also evaluated the side effects and complications of the therapy, as well as the causes of the treatment discontinuation. RESULTS: The botulinum toxin treatment was effective in 92% of the patients. It is a great importance that the therapy resulted significantly improvement in 56% of the patients. There was no significant difference neither among the types of the dystonia (cervical dystonia 87%, blepharospasm 93%, and hemifacial spasm 96%), nor among the medications (Botox 92%, Dysport 92%) in point of efficacy. Temporary weakness occurred only at 6 patients. There was neither serious side effect, nor complication related to the treatment. CONCLUSIONS: The authors can conclude that the botulinum toxin injection is effective and safe therapy, in the patients with cervical dystonia, blepharospasm, and hemifacial spasm.

Effects of 3-aminopyridine-induced seizures on platelet eicosanoid synthesis.

We investigated the influence of recurrent epileptic seizures on the arachidonic acid (AA) cascade in platelets and brain microvessels, using [(14)C]AA as a tracer substrate and chromatographic determination. The recurrent epileptic seizures of male Wistar rats were induced every second day with 3-aminopyridine (3-AP, 25 mg/kg ip) for two weeks. In the chronic 3-AP model, the earlier epileptic insults resulted in a decreased incidence of limbic seizures and higher survival rate at later administration of 3-AP. After 3-AP treatment, the formation of lipoxygenase products was unchanged, but the total amount of cyclooxygenase (COX) metabolites was decreased both in platelets and brain microvessels. The reduction in COX-mediated eicosanoid synthesis after recurrent seizures was due to the decreased synthesis of vasodilator and vasoconstrictor COX metabolites. In platelets, the 3-AP-treatment reduced the synthesis of vasodilator prostacyclin (PGI(2)), prostaglandin E(2) (PGE(2)) and 12-L-hydroxy-5,8,10-heptadecatrienoic acid (12-HHT), while the synthesis of prostaglandin D(2) (PGD(2)) remained unchanged. In isolated brain capillaries, the PGD(2), PGE(2) and 12-HHT synthesis was decreased after recurrent seizures. As for the vasoconstrictor COX metabolites, both platelets and brain microvessels synthesized significantly lesser amount of prostaglandin F(2alpha) (PGF(2alpha)) and thromboxane A(2) (TxA(2)) upon 3-AP administration. Our results indicate that platelets and isolated brain capillaries synthesize significantly lesser amount of COX metabolites after chronic 3-AP treatment. The decreased conversion of AA into different COX products may play a role in the neuroprotective/preconditional adaptation of the brain against subsequent seizures.

[The role of the antiepileptic drugs at the development of the sexual dysfunctions in male epileptic patients]. / Az antiepileptikumok szerepe a szexuális zavarok kialakulásában epilepsziás férfiaknál.

It is well known that alterations in sexual functions occur more frequently in men with epilepsy than in general population. The results of the epidemiological studies are considerably diverge from one another (3-61%), so the exact value of the incidence is not known. The most common form of sexual dysfunctions is the hyposexuality, determined as a overall reduction in sexual interest, awareness, and activity. Sexual dysfunction, as a disorder is often multifactorial, but the role of medical factors can be the most important in the development. The endocrinological disturbances occurring in epilepsy are mainly caused by the pharmacokinetic interactions among the antiepileptic medication. The enzyme inductor drugs decrease the level of free testosterone, dihydrotestosterone, follicle stimulating hormone, and luteinizing hormone, and increase the sex-hormone-binding globulin and estradiol levels. In valproate treated men significantly lower follicle stimulating hormone and luteinizing hormone concentrations, and free/total carnitine ratio, and higher dehydroepiandrosterone concentration can be detected. The enzyme inductor antiepileptic drugs can decrease the biologically active testosterone level by stimulating the aromatase and the hepatic cytochrome P450 enzymes, which can result in the development of sexual dysfunctions. Hormonal changes resulting in the alteration of the androgen synthesis and gonadotropin levels may contribute to the sexual dysfunction observed in valproate treated epileptic patients. If the role of the antiepileptic medication can be proven in the development of the sexual dysfunctions, changing in the antiepileptic drug therapy is recommended. According to evidences, the usage of oxcarbazepine and lamotrigine is not associated with changes in hormonal levels, and does not lead to alterations in sexual functions. In case of sexual dysfunctions switching from carbamazepine to oxcarbazepine, levetiracetam, or gabapentin is recommended in patients with partial epilepsy, and from valproate to lamotrigine or levetiracetam in patients with idiopathic generalized epilepsy. Enforcement of the primary prevention in the treatment of men with epilepsy is an important task of the future.

The functional significance of gap junction channels in the epileptogenicity and seizure susceptibility of juvenile rats.

PURPOSE: The functional significance of gap-junction (GJ) channels in seizure susceptibility and induction and maintenance of seizures in the developing rat brain was investigated on the 4-aminopyridine (4-AP) in vivo epilepsy model. METHODS: In electrophysiological experiments, GJs were manipulated with a blocker or opener before induction or at the active epileptic foci between postnatal days 9 and 28 (P9-28). Semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) amplification was used to measure the levels of connexin (Cx) 26, 32, 36, and 43 mRNAs at the untreated cortex or epileptic foci. RESULTS: The basic electrocorticogram (ECoG) and Cx messenger RNA (mRNA) expression patterns exhibited characteristic maturation; the 4-AP-induced epileptiform activity correlated well with these changes. Cx mRNA expressions were significantly upregulated around P16 (except for Cx26). The Cx26, 36, and 43 gene inducibility was highest around P16 and then declined significantly. In the youngest animals, the GJ opener induced rhythmic synchronous cortical activity. On maturation, the seizures became focalized and periodic; the discharges accelerated their amplitude and frequency increase. A transient decrease (P13-14) and then increase (P15-16) in seizure susceptibility were followed by a tendency to periodicity and focalization. CONCLUSIONS: The study suggests that GJ communication is involved in rhythm genesis and synchronization of cortical activity and may enhance the epileptogenicity of the developing brain.

Quinine, a blocker of neuronal cx36 channels, suppresses seizure activity in rat neocortex in vivo.

PURPOSE: The selective contribution of neuronal gap junction (GJ) communication via connexin 36 (Cx36) channels to epileptogenesis and to the maintenance and propagation of seizures was investigated in both the primary focus and the mirror focus by using pharmacologic approaches with the 4-aminopyridine in vivo epilepsy model. METHODS: ECoG recording was performed on anesthetized adult rats, in which either quinine, a selective blocker of Cx36, or the broad-spectrum GJ blockers carbenoxolone and octanol were applied locally, before the induction or at already active epileptic foci. RESULTS: The blockade of Cx36 channels by quinine before the induction of epileptiform activity slightly reduced the epileptogenesis. When quinine was applied after 25-30 repetitions of seizures, a new discharge pattern appeared with frequencies >15 Hz at the initiation of seizures. In spite of the increased number of seizures, the summated ictal activity decreased, because of the significant reduction in the duration of the seizures. The amplitudes of the seizure discharges of all the patterns decreased, with the exception of those with frequencies of 11-12 Hz. The blockade of Cx36 channels and the global blockade of the GJ channels resulted in qualitatively different modifications in ictogenesis. CONCLUSIONS: The blockade of Cx36 channels at the already active epileptic focus has an anticonvulsive effect and modifies the manifestation of the 1- to 18-Hz seizure discharges. Our findings indicate that the GJ communication via Cx36 channels is differently involved in the synchronization of the activities of the networks generating seizure discharges with different frequencies. Additionally, we conclude that both neuronal and glial GJ communication contribute to the manifestation and propagation of seizures in the adult rat neocortex.

[Pharmacotherapy of epilepsy]. / Az epilepszia gyógyszeres kezelése.

Antiepileptic drug treatment is essential and provides excellent therapeutic effects in more than the two-third of the epileptic patients. The antiepileptic drugs influence the chronic hyperexcitability of the brain developed during the epileptogenesis. As an effect, it decreases the excitability and/or increases the inhibition of the pathological cells, which prevents the precipitation of the epileptic seizure (anticonvulsive effect). The anticonvulsive effect comes into operation by the influence of the transport of one ore more ion-channels. The anticonvulsive effect is only symptomatic and it doesn't cure the disorder. The drug selection is based on the knowledge of the therapeutic markers and the effectiveness of the drug to be used. This can occur on the basis of the action of the drug or in syndrome-specific way. The pharmacokinetic properties of the drugs determine how they can be used in the practice. The drug interactions can take place in several levels. Among them, the change of the metabolism is the most important. Acute dose-dependent side effects, organ-specific chronic interactions and idiosyncratic reactions must be taken into consideration during the use of antiepileptic drugs. The patient's individual aspects must be considerably taken into account during the treatment. There are other medical areas that can benefit from the antiepileptic drugs. Among them, the most important diseases are: restless legs syndrome, neuropathic pain, trigeminal neuralgia, essential tremor, bulimia and bipolar disorders. There are other pharmacological (adrenocorticotropic hormone, immunoglobulins, neurosteroids) and dietary methods, which may be effective at certain epileptic syndromes. The principles of the pharmacotherapy have been changing continuously during the past decades and since. New drugs have been introduced into the marketing and new expectations are coming into the limelight concerning the treatment. As a consequence this will bring on the modification of antiepileptic drug therapeutic habits.