Non-Motor Symptoms in Patients with Primary Dystonia

Isolated dystonia, previously referred to as primary, is the third most common movement disorder, characterized by involuntary muscle contractions causing abnormal movements and postures with or without the presence of tremor. No matter monogenic or sporadic, the form of dystonia is a growing evidence, suggesting the presence of non-motor components to the disorder. Dystonia patients suffer from reduced quality of life, which might be related not only to the dystonic movements itself but to different non-motor symptoms and signs, as well. Based on literature review, this chapter aims to focus on the association of different types of isolated/primary dystonia (forms of focal, segmental, and generalized dystonia) with some non-motor disorders, including sleep and psychiatric disorders, cognition, as though as pain and sensory symptoms, their pathophysiological and biochemical mechanisms, relations with the symptomatic treating strategies for the abnormal movements, and specific treatment for the non-motor signs

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)

Efficacy and safety of adjunctive padsevonil in adults with drug-resistant focal epilepsy: Results from two double-blind, randomized, placebo-controlled trials

Antiepileptic drug; Antiseizure medication; TolerabilityFármaco antiepiléptico; Medicamento anticonvulsivo; TolerabilidadMedicament antiepilèptic; Medicament anticonvulsiu; TolerabilitatObjective To characterize efficacy, safety/tolerability, and pharmacokinetics of padsevonil (PSL) administered concomitantly with ≤3 antiseizure medications (ASMs) for observable focal seizures in adults with drug-resistant epilepsy in two multicenter, randomized, double-blind, placebo-controlled, parallel-group trials. Methods The phase 2b dose-finding trial (EP0091/NCT03373383) randomized patients 1:1:1:1:1 to PSL 50/100/200/400 mg or placebo twice daily (b.i.d.). The phase 3 efficacy trial (EP0092/NCT03739840) randomized patients 1:1:1:1 to PSL 100/200/400 mg or placebo b.i.d. Patients with observable (focal aware with motor symptoms, focal impaired awareness, focal to bilateral tonic–clonic) focal seizures for ≥3 years, experiencing them ≥4 times per 28 days including during the 4-week baseline period despite treatment with ≥4 lifetime ASMs including current ASMs, were enrolled. Results In EP0091 and EP0092, 410 and 231 patients, respectively, were randomized and received at least one dose of trial medication. In patients in EP0091 on PSL 50/100/200/400 mg b.i.d. (n = 80/82/81/81, respectively) versus placebo (n = 81), outcomes included percentage reductions over placebo in observable focal seizure frequency during the 12-week maintenance period: 17.2%, 19.1% (p = 0.128), 19.2% (p = 0.128), 12.4% (p = 0.248); 75% responder rates (p-values for odds ratios): 13.8%, 12.2% (p = 0.192), 11.1% (p = 0.192), 16.0% (p = 0.124) versus 6.2%; 50% responder rates: 33.8% (p = 0.045), 31.7% (p = 0.079), 25.9% (p = 0.338), 32.1% (p = 0.087), versus 21.0%; TEAEs were reported by 82.7% (67/81), 78.3% (65/83), 74.4% (61/82), 90.1% (73/81) versus 78.3% (65/83). In patients in EP0092 on PSL 100/200/400 mg b.i.d. (n = 60/56/56, respectively) versus placebo (n = 54), outcomes included percentage reductions over placebo: −5.6% (p = 0.687), 6.5% (p = 0.687), 6.3% (p = 0.687); 75% responder rates: 15.3% (p = 0.989), 12.5% (p = 0.989), 14.3% (p = 0.989) versus 13.0%; 50% responder rates: 35.6% (p = 0.425), 33.9% (p = 0.625), and 42.9% (p = 0.125) versus 27.8%; TEAEs were reported by 80.0% (48/60), 78.9% (45/57), 83.1% (49/59) versus 67.3% (37/55). Significance In both trials, the primary outcomes did not reach statistical significance in any PSL dose group compared with placebo. PSL was generally well tolerated, and no new safety signals were identified

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

Болки в шията

Цервикалният гръбнак е изключително подвижен и често се травматизира. В шията са разположени множество чувствителни към болка структури. Етиологията на болките най-често е свързана с мускулно-скелетната система и апофизеалните стави. Болките възникват остро и преминават спонтанно и рядко хронифицират. Острата идиопатична (неспецифична) болка в шията е еквивалент на идиопатичната болка в кръста и е с неясна етиология, но с мускулен произход. Освен болка и спазъм на шийните мускули не се установяват отпадни неврологични симптоми. Синдрома на увреда от камшичен удар се характеризира с увредата, настъпваща при камшичното движение на главата при инцидент с моторно превозно средство. Протича с болки в шията, отразена болка в главата или горните крайници. Носенето на шийна яка няма доказан ефект. Регионалните миофасциални синдроми обхващат големите мускули на шията и раменният пояс. Характеризират се с тригерни точки в шийните мускули, мускулен спазъм, болка и ограничени движения в шията и рамото. Дегенеративните промени в шийната област по-рядко водят до болки и компресия на нервни коренчета поради по-широкия спинален канал. Дисковата херния в шийната област, за разлика от лумбалната, не е преобладаваща причина за коренчева увреда. Цервикалната спондилоза, хипертрофията на апофизеалните стави и остеофитозата са една от най-честите причини за болки в шията. Болката е придружена от мускулен спазъм, стегнатост и ограничена подвижност на гръбнака, без отпадни неврологични симптоми. Синдромът на цервикалните апофизеални стави протича с болка в горната част на врата, ирадиираща окципитално, париетално и към ипсилатералната фронтална област. Анкилозиращият спондилит, ревматоидният артрит и polymyalgia rheumatica са честа причина за болки в шийната област. Атлантоаксиалната нестабилност протича с патологично екстензивен обем на движение, поради увреждане на трансверзалния лигамент на атласа и двете фасетъчни стави. Болките от атлантоокципиталните стави настъпват вследствие на дегенеративен артрит или травматична увреда, свързана с рязко ускоряване или намаляване на ускоряването при движение. Синдромът „шия-език” протича с внезапна едностранна остра или пробождаща и силна болка в окципиталната или в горната шийна област, придружена от изтръпване, дизестезия, абнормни усещания и и/или положение на ипсилатералната част на езика. Цервикогенното главоболие представлява болка, отразена от горната задна част на шията към главата. В заключение болките в шийната област имат различна етиопатогенеза от тези в лумбосакралната област