Trends of stroke hospitalisation and fatality rates in young vs. elderly people in Poland during 2010-2019 decade.

INTRODUCTION: Since the turn of the century, epidemiological studies have shown an increase in stroke hospitalisation rates among young adults in contrast to a decline in rates seen among the older population. The aim of the present study was to investigate the trends of stroke hospitalisation rates and case fatality ratios (CFR) over the decade starting in 2010 in different age groups of the Polish population. MATERIAL AND METHODS: The patients were identified on the basis of the Polish National Health Fund that gathers all the data of the Hospital Discharge Registry as well as the National Cause of Death Registry of patients with stroke who were hospitalised between 2010 and 2019 and who were diagnosed according to the International Classification of Diseases - Tenth Revision (ICD-10) with haemorrhagic stroke (HS; codes I61* and I62*) and ischaemic stroke (IS; codes I63*). RESULTS: From a total nationwide cohort of 799,132 stroke patients (86.2% with IS and 13.8% with HS) treated between 2010 and 2019, a group of 22,329 patients (2.79%) aged 18-44 years was selected, among whom 69.6% had IS and 30.4% had HS. We documented a statistically significant increase in the IS hospitalisation rate in young adults alongside a decrease of this rate in those aged > 64. Among young adults with IS, the highest increase (p = 0.001) was observed for those aged 35-44 in 2019 (up to 39.2), and was significant each year starting from 2017 (2017-2019: p < 0.01). In the case of HS, the annual number of patients did not change significantly. In 2019 (compared to 2010), a decrease in 30-day, 90-day and 1-year CFR was noted in all age groups of patients with IS and HS. Stroke aetiology of IS was diagnosed in 60% of patients. More than 40% of patients with IS were discharged with the diagnosis of stroke of unspecified cause. CONCLUSIONS: In the case of IS, opposite trends of hospitalisation rates in younger and older age groups were documented, with the highest increase of IS in patients aged 35-44. A decline in CFR was observed for both IS and HS in all age groups.

A viewpoint on rational and irrational fixed-drug combinations.

INTRODUCTION: Considering that there are around 30% of patients with epilepsy resistant to monotherapy, the use of synergistic combinations of antiepileptic drugs is of particular importance. This review shows most beneficial as well as irrational combined treatments both from an experimental and clinical point of view. Areas covered: Preferably, experimental data derived from studies evaluating synergy, additivity, or antagonism by relevant methods, in terms of anticonvulsant or neurotoxic effects and pharmacokinetic data have been considered. Although there have been no randomized clinical trials on this issue, the clinical data have been analyzed from studies on considerable numbers of patients. Case-report studies have been not considered. Expert commentary: The experimental data provide a strong support that co-administration of lamotrigine with carbamazepine is negative, considering the anticonvulsant and neurotoxic effects. Clinical reports do not entirely support this conclusion. Other experimentally documented negative combinations comprise lamotrigine+ oxcarbazepine and oxcarbazepine+ phenytoin. From the experimental and clinical point of view, a combination of lamotrigine+ valproate may deserve recommendation. Other most positive experimental and clinical combinations include carbamazepine+valproate, phenytoin+phenobarbital, carbamazepine+gabapentin, carbamazepine+topiramate, levetiracetam+valproate, levetiracetam+carbamazepine. Certainly, experimental data have some limitations (non-epileptic animals, acute administration of antiepileptic drugs) so all experimental recommendations need a careful clinical evaluation.

[Headaches in autoimmune diseases].

Vasculitides in autoimmune diseases are an important cause of secondary headaches. The article discusses the incidence of headache in primary and secondary vasculitides of the central nervous system. The symptoms of primary CNS vasculitis are presented. The occurrence of headache in large-vessel vasculitides, such as Takayasu arteritis and giant cell arteritis; medium-vessel vasculitides, such as polyarteritis nodosa and Kawasaki disease; and small-vessel vasculitides, such as microscopic polyangiitis, granulomatosis with polyangiitis, and eosinophilic granulomatosis with polyangiitis, are characterized. The occurrence of headache in vasculitides of different blood vessels, such as Behcet's disease and Cogan's syndrome, is presented as well. Systemic autoimmune diseases discussed in the paper are systemic lupus erythematosus, antiphospholipid antibody syndrome, rheumatoid arthritis, Sjogren's syndrome, and sarcoidosis. Vasculopathies which can mimic CNS vasculitides were discussed as well. Examples include reversible cerebral vasoconstriction, Susac's symdrome, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

[Headaches and multiple sclerosis]. / Bóle glowy a stwardnienie rozsiane.

The article discusses the possible association between multiple sclerosis (MS) and headache. MS has a broad range of neurological symptoms, but headache is not included among them. Research on the link between MS and headache focuses on primary headaches such as migraine, tension-type headache and cluster headache. Studies on the possible association between MS and migraine have had conflicting results and have found a wide range of prevalence rates for migraine in MS patients. The possible mechanisms proposed linking migraine and MS can be unidirectional, bidirectional or involving a common cause. The prevalence of TTH in MS patients is similar to that observed in the general population. Immunotherapy may play a role in inducing headache.

[Drug resistance in epilepsy]. / Lekoopornosc w padaczce.

BACKGROUND: Although there are numerous definitions of drug resistance in epilepsy it is generally accepted that drug resistance occurs when seizures persist in the presence of an optimal antiepileptic treatment. In spite of many newer antiepileptic drugs introduced into treatment, the relative number of drug-resistant patients remains approximately the same and reaches 30%. Consequently, there are a great deal of experimental and clinical studies aimed at finding mechanisms responsible for this phenomenon. Characterization of these mechanisms could result in new, more efficient treatment strategies. THE AIM OF STUDY: To review experimental and clinical data on possible mechanisms of drug resistance in epilepsy. RESULTS: An increased expression of protein drug transporters (for example, P-gp or MRP) within the blood-brain barrier or in the epileptic focus itself seems an important mechanism of drug resistance. This leads to the enhanced removal of antiepileptic drugs from the brain and subsequently, their reduced concentrations in the target tissue. Also, mutations of genes encoding GABAA receptors or ion channels may be reasons for the diminished protection of antiepileptic drugs. Some role may be ascribed to the genetic polymorphism of liver microsomal enzymes. Last but not least, use of other drugs unrelated to epilepsy (i.e. theophylline) or ingestion of stimulatory substances (f.e. caffeine) are likely to reduce the protective potential of antiepileptic drugs. CONCLUSION: In animal models of epilepsy, inhibitors of drug transporters (verapamil, probenecid) efficiently inhibit drug resistance--may be, this potential method of treatment will be positively verified in clinical trials. Initial clinical data on this issue are encouraging. Probably, the drug resistance due to methylxanthines could be stopped quite easy by replacement of this drug group with other drugs sharing other mechanisms of action and exerting similar clinical effects. The most challenging for an efficient treatment seems drug resistance due to genetic reasons.

New generation of valproic acid.

Valproic acid (VPA) is one of four first-line antiepileptic drugs (AEDs) currently established in the long-term treatment of epilepsy. Despite VPA's wide spectrum of action, in some cases its use is limited due to specific pharmacokinetics and dangerous adverse effects. These include hepatotoxicity and teratogenecity. Such limitations account for intensive research that has been carried out in order to develop new analogues or derivatives of VPA. In our review, we focus on three out of a number of substances that have been lately under investigation: NPS 1776, valrocemide and DP-VPA. These potential AEDs present both good anticonvulsive and safety profiles and seem to be more potent than the original VPA. Clinical trials, which are now ongoing, will answer the question whether or not they could become second generation of VPA.

Influence of LY 300164 alone or in combination with carbamazepine or diphenylhydantoin on the body temperature in mice.

This study was aimed at evaluating the body temperature of mice following the injection of LY 300164, an AMPA/kainate receptor antagonist, alone or in combination with carbamazepine or diphenylhydantoin. LY 300164, injected alone at the dose of 2 mg/kg, produced a potent hypothermic effect between 15 and 30 min, or 60 and 90 min, after the drug administration. The combined treatment of LY 300164 (2 mg/kg) with diphenylhydantoin (3.6 mg/kg) resulted in a significant decrease of body temperature at the time period between 0 and 30 min, whilst LY 300164 (2 mg/kg) co-administered with carbamazepine (5 mg/kg) did not affect the animal temperature. Moreover, either diphenylhydantoin (11.8 mg/kg) or carbamazepine (15.8 mg/kg) injected alone exerted the hypothermic effects elicited at times ranging between 0 and 15 min, or 60 and 90 min, after the respective drug dose administration. In conclusion, hypothermia induced by LY 300164 along with its neuroprotective effects, may be useful in various brain conditions related with neuronal loss in which hypothermia offers some profitable effects, prolonging a survival rate of neurons in the central nervous system.