AIM OF STUDY: To determine whether a high dose of levodopa-carbidopa intestinal gel (LCIG), expressed as levodopa equivalent daily dose (LE daily dose), is a risk factor for acute polyneuropathy in patients treated with LCIG. CLINICAL RATIONALE FOR STUDY: Treatment with LCIG is an effective device-assisted therapy in the advanced stages of Parkinson's Disease (PD). Polyneuropathy is a well-known complication of PD treatment. Patients treated with oral levodopa usually suffer from sub-clinical or mild chronic sensory polyneuropathy. However, severe acute polyneuropathy occurs in patients treated with LCIG, which is causally related to the treatment and leads to its immediate discontinuation. The etiology is not yet clear, but some patients with acute polyneuropathy have been given high doses of LCIG. MATERIAL AND METHODS: A retrospective multicentre study of patients treated with LCIG was performed. Patients with acute polyneuropathy were subjected to a detailed analysis including statistical processing. RESULTS: Of 183 patients treated with LCIG in seven centres, six patients (five females, median age 63 years) developed acute polyneuropathy with LCIG discontinuation. The median (interquartile range) initial and final LE daily dose in patients with and without acute polyneuropathy was 3,015 (2,695-3,184) and 1,898 (1,484-2,167) mg, respectively. The final LE daily dose of 2,605 mg cut-off had 83% sensitivity and 93% specificity for the prediction of acute polyneuropathy. CONCLUSIONS AND CLINICAL IMPLICATIONS: The risk of acute polyneuropathy in LCIG-treated patients was associated with a daily LE dose of greater than 2,605 mg or with more than a 62% increase in the daily LE dose during LCIG treatment.
- MeSH
- antiparkinsonika * škodlivé účinky aplikace a dávkování MeSH
- fixní kombinace léků * MeSH
- gely * MeSH
- karbidopa * aplikace a dávkování škodlivé účinky MeSH
- levodopa * aplikace a dávkování škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- Parkinsonova nemoc * farmakoterapie MeSH
- polyneuropatie * chemicky indukované farmakoterapie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Stereotypie jsou opakující se, rytmické, zdánlivě neúčelné pohybové vzorce. Primární stereotypie jsou typicky popisovány u zdravých dětí s normálním vývojem, stereotypie se spouštěčem v dospělosti jsou výrazně vzácnější. Prevalence primárních stereotypií se udává mezi 3 až 8 %. Sekundární stereotypie se objevují buď v důsledku senzorické deprivace, sociální izolace, nebo jako součást širší symptomatiky u mnoha, především neurovývojových, onemocnění, u psychiatrických onemocnění nebo jako součást polékových syndromů. V genezi stereotypií se zvažují jak neurobiologické mechanismy včetně genetické dispozice, tak vlivy zevního prostředí a sociálních interakcí. Základním terapeutickým postupem je edukace a behaviorální terapie, u farmakologických postupů bohužel scházejí randomizované, dvojitě zaslepené studie.
Stereotypies are repetitive, rhythmic, seemingly purposeless movement patterns. Primary stereotypies are typically described in healthy children with normal development, stereotypies with a trigger in adulthood are significantly rarer. The prevalence of primary stereotypies is reported between 3 and 8 %. Secondary stereotypies appear either as a result of sensory deprivation, social isolation or as part of broader syndroms in many, especially neurodevelopmental diseases, in psychiatric diseases or drug-induced syndromes. In the genesis of stereotypies, both neurobiological mechanisms, including genetic disposition, and the effects of the external environment and social interactions are considered. The basic therapeutic procedure are education and behavioral therapy, unfortunately there are no randomized, double-blind studies for pharmacological procedures.
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- neurodegenerativní nemoci * diagnóza farmakoterapie klasifikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Primární progresivní afázie (PPA) jsou neurodegenerativní onemocnění, která se vyznačují izolovanou alterací řeči s postupnou progresí do demence. Je jen málo údajů o individuální progresi pacientů s PPA a větší publikované studie jsou retrospektivní. Navrhovaný projekt je koncipován jako longitudinální multicentrická kohortová studie. Předpokládáme vyšetření 50-60 pacientů s PPA. Srovnávacím souborem bude 20-30 pacientů s frontotemporální demencí, 20-30 pacientů s Alzheimerovu nemocí, a 20-30 pacientů s vaskulární afázií. V současné době již disponujeme daty od 50 pacientů s mírnou kognitivní poruchou, 50 pacientů s Parkinsonovou nemocí a 50 zdravých dobrovolníků. Pacienti budou vyšetřováni neuropsychologickými testy, MRI, budou stanovovány biomarkery neurodegenerací a ve vybraných případech i neuropatologické vyšetření. Výstupem bude zlepšení časné diagnózy PPA, vytvoření baterie neuropsychologických testů pro včasnou diagnózu, lingvistická analýz subtypů PPA a zpřesnění prognostického očekávání u pacientů s PPA.; Primary progressive aphasias (PPA) are neurodegenerative disorders with an initial isolated language impairment progressing into dementia. Data about individual progression of PPA patients are sparse, as most large studies are retrospective. The project is designed as a prospective longitudinal multicenter cohort study. We emphasize to include 50-60 PPA patients, as comparative cohorts 20-30 patients with frontotemporal dementia, 20-30 Alzheimer’s disease patients and 20-30 patients with vascular aphasia. We already dispose of data from 50 mild cognitive impairment subjects, 50 Parkinson disease subjects and 50 healthy controls. All patients will be examined using neuropsychological tests, MRI, biomarkers of neurodegeneration; and in selected patients, neuropathological examination will be done. Expected outcomes include improvement of early diagnosis of PPA, composition of an appropriate neuropsychological battery for early assessment of PPA subtypes and their linguistic analysis and better prognostic estimates in PPA.
- Klíčová slova
- magnetická rezonance, magnetic resonance imaging, demence, dementia, neurodegeneration, Alzheimer's disease, Alzheimerova nemoc, progresivní afázie, neurodegenerace, frontotemporální demence, afázie, primary progressive aphasia, frontotemporal dementia, aphasia,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Neurodegenerace jsou důsledkem postupného zániku specifických skupin neuronů. Patofyziologickou podstatou je ukládání určitého specifického – pro dané onemocnění charakteristického proteinu (např. beta-amyloidu, tau proteinu nebo alfa-synukleinu) v mozkové tkáni v kombinaci s obecnými mechanismy apoptózy a autofagie (řízené smrti buňky). Správné rozpoznání neurodegenerací během života pacientů je i v současné době velmi obtížné. Kombinace dvou i více neurodegenerativních onemocnění jsou častější, než se dříve soudilo, i když zatím nejsou dostupná přesnější epidemiologická data. Překrývání neudegenerací může být příčinou rychlejšího průběhu i někdy velmi atypických klinických obrazů u řady pacientů. Je proto nutné zdůraznit nutnost provádění detailního neuropatologického vyšetření mozku pacientů a následnou retrospektivní klinicko-patologickou korelací analyzovat vliv a případně též podíl jednotlivých komorbidit na průběh onemocnění. Výsledná analýza totiž může mít u budoucích pacientů potenciální terapeutické konsekvence a být přínosná pro zpřesnění prognostických aspektů onemocnění.; Neurodegenerative diseases are serious fatal disorders caused by progressive loss of specific neuronal populations.Correct recognition of neurodegenerative dementias during the patients’ life is still very difficult.Combinations of two or more neurodegenerative diseases are far more common than previously admitted, even though more precise epidemiological data is still missing.Overlap of neurodegenerative diseases may be involved into a more rapid progression or very atypical presentation in many patients.Moreover,newly described neuropathological entities related to the aging-Aging-related tau astrogliopathy(ARTAG) or Primary age-related tauopathy(PART)-are more frequent than previously expected and till this time a precise definition of the clinical picture of these impairments is missing.The principal objective is to estimate the proportion of comorbid neurodegenerative dementias in a single centre and in a neuropathological reference laboratory based on retrospective and prospective clinic-pathological correlations in order to improve the clinical diagnosis of different diseases.
- Klíčová slova
- biomarkery, biomarkers, demence, dementia, neurodegeneration, neurodegenerace, neuropatologie, neuropathology, překrývání, overlap,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.
AIM OF THE STUDY: Comparative cross-sectional study of retinal parameters in Huntington's disease and their evaluation as marker of disease progression. CLINICAL RATIONALE FOR THE STUDY: Huntington's disease (HD) is a neurodegenerative disorder with dominant motor and neuropsychiatric symptoms. Involvement of sensory functions in HD has been investigated, however studies of retinal pathology are incongruent. Effect sizes of previous findings were not published. OCT data of the subjects in previous studies have not been published. Additional examination of structural and functional parameters of retina in larger sample of patients with HD is warranted. MATERIALS AND METHODS: This is a prospective cross-sectional study that included: peripapillary retinal nerve fiber layer thickness (RNFL) and total macular volume (TMV) measured by spectral domain optical coherence tomography (OCT) of retina, Pelli-Robson Contrast Sensitivity test, Farnsworth 15 Hue Color discrimination test, ophthalmology examination and Unified Huntington's disease Rating Scale (UHDRS). Ninety-four eyes of 41 HD patients examined in total 47 visits and 82 eyes of 41 healthy controls (HC) examined in total 41 visits were included. Analyses were performed by repeated measures linear mixed effects model with age and gender as covariates. False discovery rate was corrected by Benjamini-Hochberg procedure. RESULTS: HD group included 21 males and 20 females (age 50.6±12.0 years [mean ± standard deviation], disease duration 7.1±3.6 years, CAG triplet repeats 44.1±2.4). UHDRS Total Motor Score (TMS) was 30.0±12.3 and Total Functional Capacity 8.2±3.2. Control group (HC) included 19 males and 22 females with age 48.2±10.3 years. There was no statistically significant difference between HD and HC in age. The effect of the disease was not significant in temporal segment RNFL thickness. It was significant in the mean RNFL thickness and TMV, however not passing false discovery rate adjustment and with small effect size. In the HD group, the effect of disease duration and TMS was not significant. The Contrast Sensitivity test in HD was within normal limits and the 15-hue-test in HD did not reveal any specific pathology. CONCLUSIONS: The results of our study support possible diffuse retinal changes in global RNFL layer and in macula in Huntington's disease, however, these changes are small and not suitable as a biomarker for disease progression. We found no other structural or functional changes in retina of Huntington's disease patients using RNFL layer and macular volume spectral domain OCT and Contrast Sensitivity Test and 15-hue-test. CLINICAL IMPLICATIONS: Current retinal parameters are not appropriate for monitoring HD disease progression.
- MeSH
- biologické markery MeSH
- dospělí MeSH
- Huntingtonova nemoc * patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervová vlákna patologie MeSH
- optická koherentní tomografie * metody MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- průřezové studie MeSH
- retina patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Huntington's disease (HD) is a rare neurodegenerative disorder with protean clinical manifestations. Its management is challenging, consisting mainly of off-label treatments. OBJECTIVES: The International Parkinson and Movement Disorder Society commissioned a task force to review and evaluate the evidence of available therapies for HD gene expansion carriers. METHODS: We followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Eligible randomized controlled trials were identified via an electronic search of the CENTRAL, MEDLINE, and EMBASE databases. All eligible trials that evaluated one or more of 33 predetermined clinical questions were included. Risk of bias was evaluated using the Cochrane Risk of Bias tool. A framework was adapted to allow for efficacy and safety conclusions to be drawn from the balance between the GRADE level of evidence and the importance of the benefit/harm of the intervention. RESULTS: Twenty-two eligible studies involving 17 interventions were included, providing data to address 8 clinical questions. These data supported a likely effect of deutetrabenazine on motor impairment, chorea, and dystonia and of tetrabenazine on chorea. The data did not support a disease-modifying effect for premanifest and manifest HD. There was no eligible evidence to support the use of specific treatments for depression, psychosis, irritability, apathy, or suicidality. Similarly, no evidence was eligible to support the use of physiotherapy, occupational therapy, exercise, dietary, or surgical treatments. CONCLUSIONS: Data for therapeutic interventions in HD are limited and support only the use of VMAT2 inhibitors for specific motor symptoms. © 2021 International Parkinson and Movement Disorder Society.
Huntington ́s disease (HD) is a progressive neurodegenerative disease with onset in adulthood that leads to a complete disability and death in approximately 20 years after onset of symptoms. HD is caused by an expansion of a CAG triplet in the gene for huntingtin. Although the disease causes most damage to striatal neurons, other parts of the nervous system and many peripheral tissues are also markedly affected. Besides huntingtin malfunction, mitochondrial impairment has been previously described as an important player in HD. This study focuses on mitochondrial structure and function in cultivated skin fibroblasts from 10 HD patients to demonstrate mitochondrial impairment in extra-neuronal tissue. Mitochondrial structure, mitochondrial fission, and cristae organization were significantly disrupted and signs of elevated apoptosis were found. In accordance with structural changes, we also found indicators of functional alteration of mitochondria. Mitochondrial disturbances presented in fibroblasts from HD patients confirm that the energy metabolism damage in HD is not localized only to the central nervous system, but also may play role in the pathogenesis of HD in peripheral tissues. Skin fibroblasts can thus serve as a suitable cellular model to make insight into HD pathobiochemical processes and for the identification of possible targets for new therapies.
