The ongoing pursuit of neuroprotective therapies in Parkinson disease

Many agents developed for neuroprotective treatment of Parkinson disease (PD) have shown great promise in the laboratory, but none have translated to positive results in patients with PD. Potential neuroprotective drugs, such as ubiquinone, creatine and PYM50028, have failed to show any clinical benefits in recent high-profile clinical trials. This 'failure to translate' is likely to be related primarily to our incomplete understanding of the pathogenic mechanisms underlying PD, and excessive reliance on data from toxin-based animal models to judge which agents should be selected for clinical trials. Restricted resources inevitably mean that difficult compromises must be made in terms of trial design, and reliable estimation of efficacy is further hampered by the absence of validated biomarkers of disease progression. Drug development in PD dementia has been mostly unsuccessful; however, emerging biochemical, genetic and pathological evidence suggests a link between tau and amyloid-β deposition and cognitive decline in PD, potentially opening up new possibilities for therapeutic intervention. This Review discusses the most important 'druggable' disease mechanisms in PD, as well as the most-promising drugs that are being evaluated for their potential efficiency in treatment of motor and cognitive impairments in PD

The first experience of using kinesiotaping in the treatment of symphysiopathy in women in the second half of pregnancy

The aim of the study - to evaluate the effectiveness of kinesiotaping in reducing the level of pain in pregnant symphysiopathyЦель исследования - оценить эффективность кинезиотейпирования в снижении уровня боли при симфизиопатии беременны

Analysis of a distinct speech disorder seen in chronic manganese toxicity following Ephedrone abuse

INTRODUCTION: In the last fifteen years a new cause of chronic manganese toxicity has been recognized. It follows recreational intravenous injections of Ephedrone, synthesized from a cold remedies contained pseudoephedrine. Potassium permanganate is used as an oxidant. It presents with severe parkinsonism-dystonia and a characteristic dysarthria. OBJECTIVES: We performed a focus perceptual study of dysarthria in Ephedrone induced parkinsonism and compared the findings with the speech disorders seen in Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP). METHODS: A digital voice recording, perceptual speech analysis (Darley, 1975) [18], serial neurological assessment and Brain Magnetic Resonance (MR) imaging were performed at the Lviv regional Clinical Hospital. The results were analysed at the Institute of Neurology in London. RESULTS: Dysarthria developed after 8.5 ± 3.2 months of daily intravenous Ephedrone abuse and was an initial symptom in a third of cases. It was characterised by a robotic-flat prosody, whispering or continuous phonation, an inability to regulate pitch and volume, frozen lip articulation, a variable degree of dystonic tightness, difficulties in speech initiation and palladia, There was no nasality and swallowing was normal. In some patients speech deteriorated even after the discontinuation of Ephedrone. MR imaging, performed soon after drug cessation showed T1 signal hyperintesity in striatum and pallidum, especially in the Globus Pallidum interna. CONCLUSION: Ephedrone induced chronic manganese toxicity can lead to a mixed hypokinetic-dystonic dysarthria with a distinct dystonic pattern. Perceptual speech analysis can be a helpful ancillary investigation in the differential diagnosis of parkinsonism, and may permit the recognition of chronic manganese toxicity

Pros and cons of a prion-like pathogenesis in Parkinson's disease

Background: Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder which affects widespread areas of the brainstem, basal ganglia and cerebral cortex. A number of proteins are known to accumulate in parkinsonian brains including ubiquitin and alpha-synuclein. Prion diseases are sporadic, genetic or infectious disorders with various clinical and histopathological features caused by prion proteins as infectious proteinaceous particles transmitting a misfolded protein configuration through brain tissue. The most important form is Creutzfeldt-Jakob disease which is associated with a self-propagating pathological precursor form of the prion protein that is physiologically widely distributed in the central nervous system. Discussion: It has recently been found that alpha-synuclein may behave similarly to the prion precursor and propagate between cells. The post-mortem proof of alpha-synuclein containing Lewy bodies in embryonic dopamine cells transplants in PD patient suggests that the misfolded protein might be transmitted from the diseased host to donor neurons reminiscent of prion behavior. The involvement of the basal ganglia and brainstem in the degenerative process are other congruencies between Parkinson's and Creutzfeldt-Jakob disease. However, a number of issues advise caution before categorizing Parkinson's disease as a prion disorder, because clinical appearance, brain imaging, cerebrospinal fluid and neuropathological findings exhibit fundamental differences between both disease entities. Most of all, infectiousness, a crucial hallmark of prion diseases, has never been observed in PD so far. Moreover, the cellular propagation of the prion protein has not been clearly defined and it is, therefore, difficult to assess the molecular similarities between the two disease entities. Summary: At the current state of knowledge, the molecular pathways of transmissible pathogenic proteins are not yet fully understood. Their exact involvement in the pathophysiology of prion disorders and neurodegenerative diseases has to be further investigated in order to elucidate a possible overlap between both disease categories that are currently regarded as distinct entities

Subregional 6-[18F]fluoro-ʟ-m-tyrosine Uptake in the Striatum in Parkinson's Disease

<p>Abstract</p> <p>Background</p> <p>In idiopathic Parkinson's disease (PD) the clinical features are heterogeneous and include different predominant symptoms. The aim of the present study was to determine the relationship between subregional aromatic l-amino acid decarboxylase (AADC) activity in the striatum and the cardinal motor symptoms of PD using high-resolution positron emission tomography (PET) with an AADC tracer, 6-[¹⁸F]fluoro-ʟ-<it>m</it>-tyrosine (FMT).</p> <p>Methods</p> <p>We assessed 101 patients with PD and 19 healthy volunteers. PD was diagnosed based on the UK Brain Bank criteria by two experts on movement disorders. Motor symptoms were measured with the Unified Parkinson's Disease Rating Scale (UPDRS). FMT uptake in the subregions of the striatum was analyzed using semi-automated software for region-of-interest demarcation on co-registered magnetic resonance images.</p> <p>Results</p> <p>In all PD patients, FMT uptake was decreased in the posterior putamen regardless of predominant motor symptoms and disease duration. Smaller uptake values were found in the putamen contralateral to the side with more affected limbs. The severity of bradykinesia, rigidity, and axial symptoms was correlated with the decrease of FMT uptake in the putamen, particularly in the anterior part. No significant correlation was observed between tremors and FMT uptake.</p> <p>Conclusions</p> <p>Decrease of FMT uptake in the posterior putamen appears to be most sensitive in mild PD and uptake in the anterior putamen may reflect the severity of main motor symptoms, except for tremor.</p

Modern accents in the diagnostics of inflammatory diseases of the pelvic organs

The clinical course of inflammatory diseases of the pelvic organs (PID) is very diverse, certain difficulties in the diagnosis of acute inflammation can be caused with a sufficient combination of probable symptoms. Most of the patients are subacute or chronic course of the disease. Not timely diagnosis and incorrectly prescribed treatment favorably affects the movement of the inflammatory process in the upper genital tract.&#x0D; The diagnosis of PID in emergency rooms and clinics is often based on clinical criteria, with or without additional laboratory and visual tests. Clinical data have a sensitivity of 87% and a specificity of 50% versus 83% sensitivity and 26% specificity of endometrial culture.&#x0D; The presence of leukocytosis in peripheral blood, elevated ESR and/or the level of C-reactive protein are also markers of inflammation and may be an indicator of the severity of the disease, but they do not serve as specific signs of PID.&#x0D; The frequency of occurrence of inflammatory diseases of the reproductive system and common complications can lead to a pronounced imbalance in the reproductive potential of not only women, but also the population. The presence of a predominance of the chronic course of the disease, specialists of different profiles should have a sense of suspicion of the probable presence of an infectious agent in the pelvic organs in women of reproductive age in the presence of various non-specific complaints from the lower abdomen and the absence of other obvious reasons.&#x0D; Untimely treatment of PID is closely associated with the deterioration of the patients condition and long-term complications.&#x0D; To achieve successful attempts to prevent complications of PID, it is practically not possible, despite numerous studies.&#x0D; The widely used routine laboratory examination methods have diagnostic value only in patients with pronounced symptom complexes, while in the chronic course their significance is small.</jats:p

THE SOCIOLOGICAL ANALYSIS OF PHENOMENON OF NON-DEVELOPING PREGNANCY

The article considers problem of non-developing pregnancy as an important social occurrence progressively deteriorating level of birth rate despite achievements of modern medicine. The evaluation was implemented concerning medical social portrait of women with non-developing pregnancy. The reliable relationship is established between developed pathology of pregnancy and presence of somatic diseases, number of abortions and miscarriages and also housing conditions, public professional activity, unfavorable conditions of labor, presence of occupational hazards.</jats:p

Hand-biting and hand-waving paroxysms in epilepsy

A 20-year-old ambidextrous female student with a 15-year history of refractory seizures was admitted to the epilepsy department for a second opinion on her diagnosis and treatment. She developed frequent motor paroxysms at the age of 4-5 years, which appeared resistant to antiepileptic therapy and which have continued to the present day. Over the last 8 years she also had five generalised tonic-clonic seizures. There is a family history of epilepsy on the maternal side. The first type of episode is characterised by left-hand flickering, associated with head turning and loss of awareness. During the second type of attack the patient demonstrates vigorous hand biting which starts without warning. The patient appears disorientated subsequently. EEG telemetry was performed and confirmed the diagnosis of both epilepsy and non-epileptic attacks. Literature reports of the relevant cases are discussed

Symphysiopathy during pregnancy, assessment of risk factors

Objective: to assess the significance of clinical and anamnestic characteristics of women as risk factors for the development of symphysiopathy during pregnancy. Materials and methods: a retrospective analysis of 26 birth histories of patients with a diagnosis of symphysiopathy/symphysitis delivered in the GUZ «Clinical Maternity Hospital No. 2» in Volgograd at 38–39 weeks of pregnancy from 2016 to 2020. All patients diagnosed symphysiopathy was made at the management of pregnancy in the antenatal clinic on the basis of complaints, the data of physical examination and by ultrasound. The data of all pregnant women were ordered, encoded and entered into tables in the program MS Excel. Statistical analysis was performed with the SPSS program for windows 16.0. Results: clinically, symphysiopathy was manifested by pain in the area of the pubic in 100% of cases. According to the medical cards, only two cases (7.7%) were treated with physical therapy. The conducted statistical analysis showed that such risk factors for the development of symphysiopathy as age, parity and body mass index (BMI) do not have statistical significance as possible factors affecting the course of symphysiopathy. A statistical analysis of the possible effect of weight gain on the width of the diastasis was carried out, according to which the compared groups have a statistical difference in the width of the diastasis (p=0.007). Conclusion: the study shows that there is no significance of such clinical and anamnestic factors as age, parity, BMI for the manifestation of symphysiopathy during pregnancy. In this study, the only statistically significant criterion affecting the course of symphysiopathy is increased overall weight gain during pregnancy.</jats:p