Transient Obstructive Hydrocephalus in Patients with Intracerebral Hemorrhage: Report of Two Cases

Obstructive hydrocephalus is a relatively common complication of intraventricular hemorrhage resulting in high morbidity and mortality. We report two cases of transient obstructive hydrocephalus caused by obstruction of mesencephalic duct in patients that presented with altered consciousness which resolved spontaneously in a few hours. In very rare cases, obstructive hydrocephalus due to intraventricular hemorrhage may be transient and does not need neurosurgical or invasive procedures for lowering raised intracranial pressure, which otherwise are currently preferred treatment options.

Acute oxcarbazepine-induced hepatotoxicity in a patient susceptible to developing drug-induced liver injury.

Oxcarbazepine (OXC) is generally accepted as a drug without risk of severe drug-induced hepatotoxicity, but according to recently reported pharmacovigilance data this statement has been challenged. However, in the literature there have been no reports of acute OXC-induced hepatotoxicity without systemic manifestations of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome. We present a female with seizures one month after delivery who had borderline elevated liver enzymes prior to the initiation of OXC treatment. Two weeks after introducing OXC, highly elevated liver enzymes were found. After discontinuation of OXC the enzymes continued to rise for another week, and afterward gradually decreased. The causal relationship with OXC intake was determined to be highly probable. Two years later, the transitory elevation of liver enzymes was observed during the treatment of acute tonsilopharingitis with amoxicillin + clavulanic acid. The repeated elevation of liver enzymes related to use of different drugs might indicate patients susceptibility for drug induced liver injuries. We suggest that monitoring of liver function tests would be clinically rational for early detection of acute OXC-induced liver hepatotoxicity in the patients with clinical and/or laboratory features which might be interpreted as possible risk factors of the increased susceptibility to drug induced liver injuries.

[Non-pharmacological methods of stroke prevention]. / Nefarmakoloske metode prevencije mozdanog udara.

Stroke is a major health problem and the leading cause of functional disability, so that effective primary prevention remains the best, easiest and most cost-effective approach to reduce serious consequences of stroke. It is well known that prevention includes pharmacological and non-pharmacological methods. However, it seems that non-pharmacological methods of stroke prevention are generally neglected and placed in an inferior position in relation to pharmacological prevention. Therefore, the objective of this review is to present the most relevant literature data on non-pharmacological methods of stroke prevention and highlight their effectiveness with the use of quantitative parameters of evidence-based medicine. The main sources of data were the American, European and Croatian guidelines for stroke prevention, along with recent research results. Literature data have shown the relative risk of stroke to be greater than 2.0 in the group with unhealthy lifestyle; in fact, healthy lifestyle predicts more than twofold difference in the incidence of stroke. It is important to emphasize the public health value of non-pharmacological stroke prevention and to underline that it should be constant, irrespective of taking pharmacotherapy for stroke prevention or not. Healthy lifestyle is fundamental for non-pharmacological stroke prevention and includes healthy diet, regular physical activity, low-normal body mass index, smoking abstinence, and moderate drinking of alcohol. It is essential to inform patients on the importance, value and benefits of non-pharmacological stroke prevention, in particular when it remains the only therapeutic option in case of adverse side effects of pharmacotherapy prevention. Numerous studies demonstrated that even small lifestyle modifications could significantly reduce the risk of stroke. Therefore, it is necessary that physicians promote moderate and healthy lifestyle and habits in primary and secondary stroke prevention because there is clear evidence that it can significantly reduce the risk of stroke.

[Central sleep apnea (Ondine's curse syndrome) in medullary infarction]. / Centralna apneja u spavanju (sindrom Ondinine kletve) kod infarkta produzene mozdine.

Ondine's curse syndrome primarily refers to cases with congenital central alveolar hypoventilation, but the term can also be used for acquired cases and implies central sleep apnea that occurs as a manifestation or complication of focal lesion in the area of the dorsolateral segment of medulla oblongata. It occurs rarely, but can lead to fatal outcome. Based on our own case report, the aim of this article is to review its clinical symptoms, and appropriate diagnostic and therapeutic procedures. We present a patient who had symptoms of vascular lesion of the dorsolateral segment of the medulla, which was verified by magnetic resonance imaging. On day 12 of his hospital stay, in the early morning, rapid development of coma was observed, which was an expression of serious respiratory failure with dominant hypercapnia. In the beginning, urgent intubation and mechanical ventilation were necessary, while in the later course of the disease breathing was assisted by noninvasive methods of Bilevel Positive Airway Pressure (BiPAP) and Continuous Positive Airway Pressure (CPAP). Throughout the night, polygraph recording confirmed the diagnosis of the central sleep apnea syndrome. The course of the disease was favorable, with a very slow but constant improvement of respiratory function. According to literature data, the disease course is not always favorable. There are published cases where it was concluded that ventilatory support was no longer needed but after a long period of normal breathing hypoventilation and death occurred suddenly during sleep. The treatment of central hypoventilation consists of ventilatory support, but there were also attempts of medicamentous treatment with the common aim of raising alertness and reactibility of the automatic breathing center. It is important to emphasize that patients with the risk of central sleep apnea should not be supplied with oxygen without arterial blood gas monitoring because of the possibility of delaying the right diagnosis. The use of oxygen in patients who already have hypercapnia due to hypoventilation could further intensify hyporeactivity of the breathing center and lead to respiratory arrest.

Social and medical care of preschool children with epilepsy in Croatia: population-based survey.

BACKGROUND: Early detection of mental retardation and other epilepsy-associated impairments is essential for successful medical and social care of children with epilepsy; the corresponding information for children in Croatia has not yet been known. AIMS OF THE STUDY: To obtain the basic information of epilepsy-associated disability in preschool children, and fundamentals of their medical and social care. METHODS: Data about mental retardation and other associated impairments (motor, speech, seeing, hearing), antiepileptic drug therapy and diurnal residence were collected by means of questionnaires completed by physicians working in primary health care (PHPs). Only children (0-7 years) with active epilepsy confirmed previously by neuropaediatricians were included. RESULTS: A total of 37 PHPs provided the required data for 116 children. One or more impairments were found in 56% children; most frequent were motor impairments (47%), speech impairments (42%) and mental retardation (40%). The regular kindergarten attendance rate of children without impairment (33%) was not different from the children without epilepsy, but high proportion (76%) of children with impairment stayed with their families during weekdays. In this subgroup monotherapy was more rarely used (64% vs. 90% in children without impairment (p<0.01)). Valproate was predominantly used (56%) in children with and without impairment; lamotrigine was more frequently used in the former subgroup (p<0.01). CONCLUSIONS: Existence of associated impairments has significant impact on medical and social care in preschool children with epilepsy. These children need an early diagnosis and consecutive multidisciplinary care of their intellectual and body impairments, as well as problems in social development.

Age-related pattern of the antiepileptic drug utilization in active epilepsy: a population-based survey.

The aim of this study was to investigate the relationship between antiepileptic drug (AED) utilization and patient age in a population of patients treated by primary health care physicians. Data were collected by using questionnaires completed by family physicians and paediatricians working in primary health care. Only patients with active epilepsy confirmed previously by neurologists or neuropaediatricans were included. One hundred and twenty-three physicians provided the requested data for 966 patients (range 1-92 years). Most frequently prescribed AEDs were barbiturates (BARB) (37%) and carbamazepine (CBZ) (37%). Valproic acid derivates (VPA) were prescribed in 28%, but the rate was higher (51%) in children. By calculating the correlation between age and the prescription of single AEDs across the whole sample, linear correlations were found for BARB (r = 0.94; p < 0.01), VPA (r = -0.93; p < 0.01) and for topiramate (TPM) (r = -0.90; p < 0.01). Since our results showed significant correlations between age and the use of the majority of AEDs, we concluded that the age may be considered a methodological bias in the presentation of data. Therefore we calculated AED utilization as the age-adjusted prevalence rates (per/1000 inhabitants). For the most commonly prescribed AEDs they were: BARB 1.8 (95% CI 1.6-2.0), CBZ 1.9 (95% CI 1.7-2.1), VPA 1.3 (95% CI 1.1-1.5), lamotrigine (LTG) 0.7 (CI 95% 0.6-0.8), TPM 0.6 (CI 95% 0.5-0.7). In conclusion, the age of patients has a significant impact on the prescription patterns not only between children and adults, but at every age. Therefore we suggest that reporting of AED utilization pattern should also include age-standardized prevalence rates of individual AED utilization.

[Guidelines for management of epilepsy--commentary on Scottish ("SIGN") guidelines]. / Smjernice za lijecenje epilepsije--osvrt na skotske smjernice "SIGN".

The choice of AED (antiepileptic drug), worldwide and in Croatia, is been still based on the physician's subjective decision, personal experience, knowledge and marketing pressure made by big pharmaceutical industries. Therefore, according to some opinions, there is a need of treatment guidelines for epilepsy that would provide relevant information based on scientific evidence on the efficacy, tolerability and safety of AEDs. The guidelines, published by a competent source, should be designed as to allow for easy access to the information on the best practice in specific cases. An extensive background literature review was made to identify such a type of guidelines for the management of epilepsy. The literature review revealed a number of references with the recommendations for treating epilepsy in different groups of patients and from various, specific aspects of epilepsy treatment. However, only one comprehensive set of guidelines for the diagnosis and treatment of epilepsy treatment was found, i.e. the evidence-based guidelines published by the Scottish Intercollegiate Guidelines Network (SIGN). The development of this set of guidelines is quite extensively described in order to illustrate how rigorous and long-lasting the process was, including a great number of health professionals at the national level. Such a type of well designed guidelines facilitates access to highest educational standards for all professionals involved in the primary and secondary care of people with epilepsy. However, it is clear that guidelines can fully replace the standards of clinical practice based on critical evaluation and integration of all clinical data of each individual patient. No guidelines can replace the physician's obligation to keep informed of the novel achievements in the epileptology either.

[Pathophysiologic basis of the treatment of neurogenic pain]. / Patofizioloske osnove lijecenja neurogene boli.

According to the International Association for the Study of Pain (IASP) neuropathic pain is "pain initiated or caused by a primary lesion or dysfunction or transitory perturbation in the peripheral or central nervous system". Neuropathic pain is usually classified according to the etiology, location of the lesion, and pain characteristics--individual symptoms and signs, but also according to the possible mechanisms involved. Identifying the underlying pain mechanisms during the diagnosis becomes essential for treatment strategies. The clinical picture of neuropathic pain is similar in many cases, and clinical features include: ongoing spontaneous or evoked pain in an area with sensory loss, positive sensory symptoms such as allodynia and hyperalgesia, wind-up pain following repetitive stimulation, referred pain and abnormal sympathetic activity. The understanding of the mechanisms underlying neuropathic pain has increased over the last decade. The primary pathophysiologic mechanisms that produce pain are: nociceptor sensitization, nerve trunk inflammation, sympathetic nervous system involvement, ectopic neuronal discharges, pathologic synaptic reorganization--neuroplasticity and central sensitization. In most clinical features, there is a complex interaction that involves peripheral and central nervous system rather than a single mechanism. Because numerous mechanisms are implicated, the traditional approach to pain control using single drug therapy may not be most effective, and therapeutic combinations are a better choice. Neuropathic pain is poorly responsive to conventional analgesics. In spite of a variety of drug classes used to treat neuropathic pain including antidepressants, anticonvulsants, antiarrhythmics, opioids, local anesthetic blockers, neuropathic pain remains difficult to treat. The possibility to select specific drugs and treatments for the individual patient lies in elucidating the relationships between clinical neuropathic states and underlying pathophysiologic changes. Progress in defining the mechanisms involved in neuropathic pain, based on further clinical studies and fundamental investigations, will improve therapeutic management of neuropathic pain.

Increase of classical antiepileptic drug utilization in Croatia during the process of introducing the new generation of drugs.

During the last decade the process of introducing the new generation of antiepileptic drugs (AEDs) has substantially changed the ways of treating epilepsy. Although a great deal of information about the role of new drugs has been accumulated, much less attention was paid to the impact of the new generation of AEDs on the utilization of classical AEDs. In order to detect the relation between the new and classical AEDs, the data about drug consumption in Croatia in the period 2000-2002 were analyzed. The main results indicated that the growth utilization rate (15%) was more the result of increasing consumption of the classical antiepileptic substances (in almost 2/3). It has been discussed that one of the possible interpretations for this phenomenon could lie in the fact that the continuing process of introducing the new AEDs was accompanied by a great number of educational activities. These activities have led to greater awareness of the facilities in treating epilepsy and consequently to a more active therapeutic approach, which encompassed both generations of drugs, even more the older one.