Национален консенсус за диагностика, лечение, проследяване и профилактика на хередитарната транстиретиновата амилоидоза

Амилоидозите са широк спектър от заболявания, дължащи се на промени в белтъчната структура, в резултат на което нормално разтворим тетрамерен белтък след дестабилизация на четвъртичната структура и последващ разпад до свободни мономери образува неразтворими извънклетъчни фибрилни депозити, което води до органна дисфункция. Всички видове амилоид съдържат един основен фибрилен протеин, който определя вида на амилоида, както и по-малки компоненти. Над 20 различни фибрилни протеина, асоциирани с амилоидози са описани при хора, всяка от които има различна клинична картина. Един такъв белтък, който формира човешки амилоидни фибрили, е транстиретина (Ando Y. и сътр. 2005). TTР действа като транспортен белтък за тироксин в плазма. TTР също транспортира ретинол (витамин А) чрез свързването му с ретинол-свързващия протеин. Той циркулира като тетрамер от четири идентични субединици. TTР може да бъде открит в плазмата и ликвора. Синтезира се главно в черния дроб и хориоидния плексус на мозъка и в по-малка степен - в ретината. Генът TTР е локализиран върху дългото рамо на хромозома 18 и съдържа 4 екзона и 3 интрона. Системните амилоидози се означават с главна буква А (за амилоид), следвана от съкращението за химическата същност на фибрилния протеин. Така например, TTР амилоидоза се съкращава ATTР, а амилоидоза при отлагане на леките вериги на имуноглобулините – AЛ (Saraiva M. и сътр., 1984; Connors L. и сътр., 2003; Ando Y. и сътр. 2005). Класифицирането на откритите генетични варианти е от изключително значение за молекулярно-генетичните тестове и тяхната интерпретация. Оценката на патогенността на даден генетичен вариант трябва да се извършва на базата на научни доказателства и според унифицирана номенклатура и правила. Във връзка с това, широко използваните до момента термини мутация и полиморфизъм са заменени с класификация на генетичните варианти, според която се обособяват 5 категории: патогенен, вероятно патогенен, вариант с неясно клинично значение, вероятно непатогенен и непатогенен (Richards S. и сътр., 2015; Nykamp K. И сътр., 2017)

Clinical profile of levodopa-carbidopa-entacapone intestinal gel infusion in patients with advanced Parkinson’s disease

Introduction: Parkinson’s disease in its advanced stage is a progressive condition that can be treated with levodopa. The long-term complications of this treatment are difficult to manage. A new device-aided therapy has recently been developed to minimize these effects. Aim: The purpose of this study was to assess the efficacy and safety of the intestinal gel containing levodopa - carbidopa - entacapone, as well as to see if it had any impact on the disease’s non-motor symptoms. Additionally, we sought to identify the criteria for selecting among the various treatments that were offered. Materials and methods: This study includes the first five patients who started receiving the levodopa-carbidopa-entacapone gel for Parkinson’s disease in the Department of Neurology and Psychiatry at St Naum University Hospital for Active Treatment in Sofia, Bulgaria. To evaluate the influence of motor and non-motor symptoms of the disease, we used neurological examination and the Movement Disorder Society - Unified Parkinson’s Disease Rating Scale. The Parkinson’s Disease Quality of Life Questionnaire was used to assess the quality of life of the patients. Results: All patients showed improvement in their motor functions, quality of life, and sleep problems in comparison with those receiving oral levodopa. No patient experienced an increase in the dyskinesias. The postural stability continued to be impaired. For now, the medication has shown a protective effect against the levodopa-induced polyneuropathy. The main side effects were diarrhea and weight loss. Conclusions: Levodopa-carbidopa-entacapone therapy is a promising new modality of treatment for advanced Parkinson’s disease. The medication has been found to improve the patients’ motor functions and exert a positive effect on some non-motor symptoms. The drug has shown a good safety profile and tolerance. There is still a lack of clear criteria for choosing between the levodopa-carbidopa-entacapone and levodopa-carbidopa intestinal gels

Prevalence of claw disorders in dairy farms with tie stalls

In intensive rearing conditions, dairy cows are exposed to many factors that can cause health disorders and significant economic loses. Today, claw diseases are the main problem in high-milk cow's herd, along with metabolic diseases, mastitis and reproduction disorders. Claw diseases can have direct effects on reproductive parameters. The aim of our research was to determine the frequency of certain diseases of the locomotor apparatus of dairy cows on farms with tie stall system. In the period of two years, a total of 37,893 cows were examined, wherein the following has been found: Laminitis in 34,217 cows (90.30%), Dermatitis interdigitalis in 25,876 cows (68.29%), Dermatitis digitalis in 11,817 cows (31.18%), Rusterholz ulcer in 8,272 cows (21.83%), Fibroma in 3063 cows (8.08%), and Panaritium in 618 cows (1.63%). The results show that laminitis dominate in the herds. Considering the etiology of diseases determined at the farms it is primarily to focus on preventing the formation of metabolic disorders and adequate nutrition of the animals, and then on the improvement of housing conditions and the regular implementation of measures to prevent the spread of infectious claw diseases

EAN Guideline on Palliative Care of People with Severe, Progressive Multiple Sclerosis

Background and Purpose: Patients with severe, progressive multiple sclerosis (MS) have complex physical and psychosocial needs, typically over several years. Few treatment options are available to prevent or delay further clinical worsening in this population. The objective was to develop an evidence-based clinical practice guideline for the palliative care of patients with severe, progressive MS. Methods: This guideline was developed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Formulation of the clinical questions was performed in the Patients–Intervention– Comparator–Outcome format, involving patients, carers and healthcare professionals (HPs). No uniform definition of severe MS exists: in this guideline, constant bilateral support required to walk 20m without resting (Expanded Disability Status Scale score >6.0) or higher disability is referred to. When evidence was lacking for this population, recommendations were formulated using indirect evidence or good practice statements were devised. Results: Ten clinical questions were formulated. They encompassed general and specialist palliative care, advance care planning, discussing with HPs the patient’s wish to hasten death, symptom management, multidisciplinary rehabilitation, interventions for caregivers and interventions for HPs. A total of 34 recommendations (33 weak, 1 strong) and seven good practice statements were devised. Conclusions: The provision of home-based palliative care (either general or specialist) is recommended with weak strength for patients with severe, progressive MS. Further research on the integration of palliative care and MS care is needed. Areas that currently lack evidence of efficacy in this population include advance care planning, the management of symptoms such as fatigue and mood problems, and interventions for caregivers and HPs

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the “patient journey”) with perplexing obstacles. High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary. The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded. It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses

Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis

Background and purpose: Patient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS. Methods: A mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers. Results: Of 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre-specified topics (from 89% for ‘advance care planning’ to 98% for ‘multidisciplinary rehabilitation’), and <5% replied ‘I prefer not to answer’ to any topic. There were 569 free comments: 182 (32%) on the pre-specified topics, 227 (40%) on additional topics (16 guideline-pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient-important outcomes and of taxing issues. Conclusions: Multiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient-important outcomes

Mezencefalni oblik meningoencefalitis a u bolesnice s HL A-B51 beh cetovom bolešću: prikaz slučaja

This case report is a detailed description of the clinical, laboratory, imaging and therapeutic characteristics of the sixth patient with neuro-Behcet’s disease reported by Bulgarian authors. The diagnosis was made in accordance with the international diagnostic criteria for Behcet’s disease and was verified by skin biopsy. Therapeutic response was followed up by clinical and magnetic resonance imaging data for 6 months. Discussed are differences in the classical Behcet’s disease presentation and other neuro-Behcet’s disease cases found in Bulgaria. The current case supports the wide clinical heterogeneity of the disorder and the variety of therapeutic options.U ovom prikazu slučaja daje se iscrpan opis kliničkih, laboratorijskih, slikovno prikaznih i terapijskih značajka šestog bolesnika s neuro-Behcetovom bolešću o kojem izvješćuju bugarski autori. Dijagnoza je postavljena na osnovi međunarodnih dijagnostičkih kriterija za Behcetovu bolest i potvrđena biopsijom kože. Odgovor na terapiju pratio se kliničkim podacima i nalazima magnetske rezonancije kroz 6 mjeseci. Raspravlja se o razlikama u manifestiranju klasične Behcetove bolesti i drugim slučajevima neuro-Behcetove bolesti u Bugarskoj. Prikazani slučaj govori u prilog velike heterogenosti ove bolesti te o potrebi vrlo raznovrsnih terapijskih pristupa