Antinociceptivni učinak botulinum toksina TIP-A u terapiji boli i glavobolje

Since its development for clinical use in 1980s botulinum toxin, the most potent biological toxin known to man has become a useful drug in various field of medicine. It was initially used to treat neurological disorders characterized by excessive muscle contractions. Since many patients report alleviation of pain before the muscle relaxing effect of botulinum toxin type-A has started, a direct analgesic action of Botulinum toxin has been discussed. There have been a number of recent investigations concerning the efficacy of botulinum toxin type-A applications for treatment of headache and chronic pain. Most of the known effect of botulinum toxin has been attributed to its ability to inhibit the release of acetylcholine from cholinergic nerve terminal. However, this effect alone does not explain the apparent antinociceptive effect of botulinum toxin. Other peripheral and central neurogenic effect should be considered. Current data suggest that Botulinum toxin is safe and effective in headache and pain treatment if used in specialist centres by experienced doctors.Nakon razvoja botulinum toksina za kliničku primjenu 80-tih godina, ovaj za čovjeka najpotentniji biološki otrov našao je primjenu u raznim granama medicine. Prva upotreba botulinum toksina bila je u neurološkim poremećajima karakteriziranim mišićnim spazmom i nekontroliranim kontrakcijama poput distonije. Zapaženi učinak na smanjenje boli prije pojave mišićne relaksacije ukazao je na direktni analgetski učinak botulinum toksina na patogenezu boli. Javljaju se zatim brojna klinička zapažanja o učinkovitosti botulinum toksina u liječenju glavobolje i kronične boli. Većina poznatih učinaka botulinum toksina na relaksaciju mišića pripisuje se učinku na otpuštanje acetilkolina na neuromuskularnoj sinapsi. Kako se ovim djelovanjem ne može objasniti njegov antinociceptivni učinak brojni periferni i centralni mehanizmi djelovanja botulinum toksina se istražuju. Sadašnji rezultati kliničke primjene ukazuju da je botulinum toksin siguran i djelotvoran lijek u liječenju glavobolje i nekih oblika kronične boli otpornih na standardne oblike liječenja, ukoliko se primjenjuje u specijaliziranom centru od strane iskusnih liječnika

Restless Legs Syndrome

Being of the most frequent causes of insomnia, which in the end leads to chronic fatigue, inadequate performance of daily activities, and serious disruption of quality of living, restless legs syndrome (RLS) is nowadays not only a serious medical problem but a socio-economical one as well. Prevalence of the disorder in general population is estimated at 5 to 15%. Family history is positive in over 50% of idiopathic RLS patients which points to genetic basis of the disorder. The characteristics of the secondary or acquired form of RLS are symptoms that start later in life as well as a rapid progression of the disease. On the other hand, idiopathic RLS more often starts at a younger age and the prognoses are better. Over twenty disorders and conditions are brought in connection with secondary RLS. Although the cause of primary RLS is still unknown, there is a strong connection between central metabolism of iron as well as dopamine levels and RLS manifestation. A differential diagnosis of RLS includes a wide specter of motor and sensory disorders. Diagnosis is based on clinical features and the history of disease. To correctly diagnose idiopathic RLS one must first eliminate secondary causes of RLS and then also exclude any disorders with clinical features that mimic those of RLS. It has been estimated that some 20 to 25% of patients need pharmacological therapy. Best initial therapy is the application of nonergot dopamine agonists. Anticonvulsants, benzodiazepines and opioides can be given to patients who are refractory to dopaminergic therapy, those suffering from RLS with emphasized painful sensory component and those with RLS connected with insomnia

Botulinum toxin type A in motor nervous system: unexplained observations and new challenges

In the motor system, botulinum toxin type A (BoNT/A) actions were classically attributed to its well-known peripheral anticholinergic actions in neuromuscular junctions. However, the enzymatic activity of BoNT/A, assessed by the detection of cleaved synaptosomal-associated protein 25 (SNAP-25), was recently detected in motor and sensory regions of the brainstem and spinal cord after toxin peripheral injection in rodents. In sensory regions, the function of BoNT/A activity is associated with its antinociceptive effects, while in motor regions we only know that BoNT/A activity is present. Is it possible that BoNT/A presence in central motor nuclei is without any function? In this brief review, we analyze this question. Limited data available in the literature warrant further investigations of BoNT/A actions in motor nervous system

Oxidative stress parameters in plasma of Huntington's disease patients, asymptomatic Huntington's disease gene carriers and healthy subjects : a cross-sectional study

BACKGROUND : Animal data and postmortem studies suggest a role of oxidative stress in the Huntington's disease (HD), but in vivo human studies have been scarce. ----- AIM : To assess the presence of oxidative stress in HD patients and its occurrence relative to clinical symptoms. ----- METHODS : Oxidative stress markers were determined in plasma of HD patients (n = 19), asymptomatic HD gene carriers (with > 38 CAG repeats) (n = 11) and their respective sex and agematched healthy controls (n = 47 and n = 22) in a cross-sectional study. ----- RESULTS : With adjustment for age and sex, HD patients had higher plasma lipid peroxidation (LP) levels (ratio 1.20, 95% CI 1.09 to 1.32, p < 0.001) and lower reduced glutathione (GSH) levels (ratio 0.72, CI 0.55 to 0.94, p = 0.011) than their age and sex-matched controls. Although considerably younger, HD gene carriers did not differ from HD patients regarding LP and GSH levels, and had higher plasma LP (ratio 1.16, CI 1.02 to 1.32, p = 0.016) and lower GSH than their matched controls (ratio 0.73, CI 0.5 to 1.05). They had higher LP (ratio 1.18, CI 1.02 to 1.34, p = 0.019) and lower GSH (ratio 0.75, CI 0.51 to 1.11) than the healthy subjects matched to HD patients. ----- CONCLUSIONS : Oxidative stress is more pronounced in HD patients and asymptomatic HD gene carriers than in healthy subjects. Differences in plasma LP and GSH are in line with the brain findings in animal models of HD. Data suggest that oxidative stress occurs before the onset of the HD symptoms

HUNTINGTON’S DISEASE

Huntingtonova bolest i/ili koreja (HD) autosomno je dominantna neurodegenerativna bolest koja nikada ne preskače generacije. Prvi ju je opisao George Huntington 1872. godine. Prevalencija u svijetu je 8–10 na 100 000 stanovnika, dok je u nas objavljeno 4,46 na 100 000 stanovnika. Započinje uglavnom između 30. i 50. godine života i završava smrtno za 15–20 godina. Bolest je to ponavljanja tripleta CAG, a karakterizira ju ekspanzija poliglutaminskog slijeda. Broj trinukleotidnih CAG-ponavljanja negativno korelira s dobi javljanja prvih simptoma, kao i s težinom kliničke slike. Za sada ne postoji selektivna terapija Huntingtonove koreje, a kao simptomatsko liječenje najdjelotvorniji su blokatori dopamina.Huntington’s disease and/or chorea (HD) is autosomal dominant neurodegenerative disease that never skips generations. The first description was provided by George Huntington in the year 1872. Its prevalence in the world is 8–10 per 100000 inhabitants and in Croatia 4.46 per 100 000 inhabitants. It starts between 30 and 50 years of age and ends after 15–20 years with death. It is a disease of CAG triplet repeats and is characterized by poliglutamine repeats. The number of CAG trinucleotid repeats correlates with the age of the onset of the first symptoms, as well as with the clinical picture. The selective therapy for Huntington’s chorea still does not exists and for symptomatic treatment the blockers of dopamine have turned out to be the most useful