La nuova frontiera dei dispositivi indossabili nella ricerca sulla malattia di Parkinson: gli sviluppi e le prospettive nello studio del sonno

La malattia di Parkinson, seconda tra le malattie degenerative più comuni, ha basato per anni la diagnosi e le valutazioni terapeutiche su scale di misura soggettive, di modesta accuratezza e limitate all’utilizzo clinico. Per questo motivo, alla luce di nuove tecnologie emergenti ed efficaci, questa tesi si propone di analizzare lo stato dell’arte dei dispositivi indossabili per la ricerca sul Parkinson e i suoi disturbi. Dopo una breve introduzione, la narrazione prende avvio, nel primo capitolo, con la descrizione della malattia seguita dai trattamenti curativi più utilizzati. Nel secondo capitolo verranno trattati i metodi di diagnosi, a partire dalle scale di valutazione qualitative per poi proseguire con una breve rassegna dei componenti e dei nuovi sensori utilizzabili per ottenere misurazioni quantitative. Questa descrizione sarà fondamentale per poter comprendere il funzionamento dei dispositivi che verranno successivamente citati. Il terzo capitolo si focalizza sulla sintomatologia del Parkinson e sulla rassegna dei dispositivi innovativi destinati alla diagnosi, al monitoraggio e alla cura, partendo dai sintomi motori più comuni ed evidenti, fino ad arrivare alle manifestazioni non motorie silenziose e subdole. Infine, la tesi si focalizzerà in particolar modo sul sonno. Dopo un’analisi della struttura del sonno, si tratteranno le metodiche più utilizzate fino ad oggi per lo studio dei disturbi notturni. Successivamente si proporranno alcuni nuovi dispositivi indossabili innovativi e li si metterà a confronto con i metodi tradizionali per analizzarne le potenzialità, gli svantaggi e i possibili sviluppi futuri. La tesi, nel suo complesso, si pone l’obiettivo di illustrare come, nella ricerca sul Parkinson, lo sviluppo di nuove tecnologie indossabili possa rappresentare un punto di svolta e di sostegno per la valutazione, la diagnosi, la cura della malattia per i clinici, i pazienti e chi se ne prende cura.

L’effetto della tossina botulinica nel trattamento della distonia cervicale in paziente con malattia di Parkinson: un case report

Background L’utilizzo della tossina botulinica in caso di problematiche legate a distonia muscolare sta assumendo sempre più validità nel processo decisionale della scelta della terapia. Attraverso il continuo miglioramento delle strategie di indagine della muscolatura responsabile del disturbo e delle tecniche di inoculazione, infatti, questa pratica si sta avviando all’essere ritenuta il gold standard in caso di distonia. Obiettivo Valutare il dolore, la mobilità, la soggettiva impressione di cambiamento e la qualità di vita in una donna affetta da distonia cervicale secondaria a malattia di Parkinson trattata attraverso inoculazione di tossina botulinica nella muscolatura del collo Materiali e Metodi È stata selezionato un soggetto di 72 anni con malattia di Parkinson in fase avanzata e distonia cervicale secondaria alla malattia stessa, che ha ricevuto indicazione al trattamento con tossina botulinica di tipo A. La donna è stata valutata tramite la somministrazione di scale di misura validate, da un minimo di 3 settimane ad un massimo di 90 giorni dall’ultima inoculazione di tossina botulinica, in modo tale da indagare il reale vantaggio per la salute della donna in termini di ‘beneficio avvertito’ in periodi diversi. Risultati Al termine della sperimentazione, la donna presenta un globale miglioramento della sua condizione, osservabile tramite l’incremento dei punteggi delle misure di outcome rispetto alla rilevazione pre-inoculazione di tossina botulinica. Conclusioni In questa sperimentazione il trattamento della distonia cervicale secondaria a malattia di Parkinson dimostra un effetto benefico che si evidenzia in particolare nella mobilità cervicale, grazie al rilassamento della muscolatura che prima ne limitava il movimento. Inoltre, si è rivelato molto utile nel miglioramento della qualità della vita. Sono tuttavia necessari ulteriori studi a dimostrazione dei reali effetti.

Strategie terapeutiche nel trattamento riabilitativo del soggetto affetto da Malattia di Parkinson: Scoping Review

Background: La Malattia di Parkinson è una malattia neurodegenerativa che dà disturbi del movimento tipici: tremore a riposo, ipocinesia o bradicinesia, rigidità e instabilità posturale; inoltre, include anche disturbi non motori quali: ansia, depressione, disturbi del sonno, disfagia, disartria e deterioramento cognitivo. L’insieme dei sintomi motori e non motori influenza la quotidianità del paziente, riduce la partecipazione e la qualità di vita in tutte le fasi della malattia. La riabilitazione motoria può aiutare a mitigare gli effetti dei sintomi motori e migliorare la qualità della vita del soggetto con PD[6,7], ma non esiste un protocollo univoco per il trattamento di questa malattia. Obiettivo: l’obiettivo di questa Scoping Review è di individuare strategie terapeutiche alternative al trattamento convenzionale nel percorso riabilitativo del paziente affetto da Malattia di Parkinson. Disegno dello studio: sono stati presi in considerazione studi pubblicati tra il 2020 e il 2022 su diverse attività non tradizionali proposte a pazienti con Parkinson. Le banche dati utilizzate sono PubMed, PEDro e Cochrane Library. Sono stati posti come criteri di inclusione: soggetti esclusivamente con Malattia di Parkinson di età > 18 anni e articoli in lingua inglese. Sono stati inclusi quindi Review, RCT e articoli di giornali che soddisfacessero la checklist della PRISMA Extension per le Scoping Review. Risultati: al termine della selezione, sono stati inclusi 6 studi che facevano riferimento ad attività come il ballo, l’arrampicata sportiva, l’esercizio in acqua, lo Yoga, il Nordic Walking e la teleriabilitazione nel PD. Conclusioni: la letteratura analizzata fornisce buoni risultati legati alle attività per il trattamento di sintomi motori e non motori del soggetto con PD. Tuttavia, gli studi hanno riportato la necessità di eseguire ulteriori prove per una conferma dell’efficacia statisticamente significativa sui disturbi del PD, con gruppi di pazienti più ampi.

Tremor essencial X doença de Parkinson

O material é componente do Curso de Especialização em Saúde da Pessoa Idosa da UNA-SUS/UFMA (Unidade 02, do módulo 07). Trata-se de um diagrama que apresenta as diferenças entre tremor essencial e doença de Parkinson.

Doença de Parkinson

'Doença de Parkinson' é a segunda lição da unidade "Condições Crônicas II" do Módulo 07 do Curso de Especialização em Saúde da Pessoa Idosa da UNA-SUS/UERJ "Principais Agravos Crônicos de Saúde da Pessoa Idosa". Nesta lição discutiremos a intitulada doença como condição crônica de alta prevalência e impacto no cuidado do indivíduo idoso.

Segunda opinião formativa: o que é a Síndrome de Wolff-Parkinson-White?

Em 1930, Louis Wolff, John Parkinson e Paul Dudley White publicaram uma série de casos de pacientes com paroxismos de taquicardia cujo ECG basal mostrava um intervalo PR curto e um padrão de bloqueio de ramo. A síndrome de Wolff-Parkinson-White (WPW) acontece quando existem vias acessórias que promovem uma pré-excitação ventricular: fibras anormais, congênitas, conectam o átrio ou a junção AV ao ventrículo, fora do sistema His-Purkinje. O impulso elétrico será transmitido sem o retardo do NAV, e haverá um by-pass com ativação elétrica prematura do ventrículo. A pré-excitação ventricular determina três principais alterações no ECG: 1. Intervalo PR curto, menor do que 120 ms nos adultos ou 90 ms nas crianças; 2. QRS alargado (duração maior do que 120 ms), com um empastamento em sua porção inicial (onda delta) e porção final normal; tal padrão acontece por uma fusão entre a ativação inicial causada pela pré-excitação (com condução intraventricular lenta fibra a fibra) e a ativação final, pelo sistema especializado His-Purkinje. 3. Alterações secundárias do ST-T, geralmente opostas à polaridade da onda delta. Padrão de WPW vs. Síndrome de WPW: é importante diferenciar o padrão eletrocardiográfico de pré-excitação que acontece em indivíduos assintomáticos do diagnóstico da síndrome de WPW: a síndrome só existe quando, além do padrão descrito, há taquiarritmias sintomáticas. O padrão de WPW é raro, e a síndrome mais rara ainda, com uma prevalência em torno de 1,5/100. Embora o prognóstico seja usualmente excelente, a morte súbita pode acontecer em cerca de 0,1% dos pacientes, e geralmente está associada a fibrilação atrial com resposta ventricular muito rápida, que se degenera em taquicardia ventricular. Pacientes com padrão de pré-excitação ao ECG e aqueles com a síndrome de WPW devem ser referendados ao cardiologista. A indicação de Holter, teste ergométrico e, sobretudo do estudo eletrofisiológico (diagnóstico e para ablação das vias acessórias) será definida conforme as diretrizes e a avaliação cuidadosa do paciente em questão.

Rotenone Exerts Similar Stimulatory Effects On H2o2 Production By Isolated Brain Mitochondria From Young-adult And Old Rats.

Chronic and systemic treatment of rodents with rotenone, a classical inhibitor of mitochondrial respiratory complex I, results in neurochemical, behavioral, and neuropathological features of Parkinson's disease. The aim of the present study was to evaluate whether brain mitochondria from old rats (24 months old) would be more susceptible to rotenone-induced inhibition of oxygen consumption and increased generation of H2O2 than mitochondria from young-adult rats (3-4 months old). Isolated brain mitochondria were incubated in the presence of different rotenone concentrations (5, 10, and 100nM), and oxygen consumption and H2O2 production were measured during respiratory states 3 (ADP-stimulated respiration) and 4 (resting respiration). Respiratory state 3 and citrate synthase activity were significantly lower in mitochondria from old rats. Mitochondria from young-adult and old rats showed similar sensitivity to rotenone-induced inhibition of oxygen consumption. Similarly, H2O2 production rates by both types of mitochondria were dose-dependently stimulated to the same extent by increasing concentrations of rotenone. We conclude that rotenone exerts similar effects on oxygen consumption and H2O2 production by isolated brain mitochondria from young-adult and old rats. Therefore, aging does not increase the mitochondrial H2O2 generation in response to complex I inhibition.

Survival and Neuronal Differentiation of Mesenchymal Stem Cells Transplanted into the Rodent Brain Are Dependent upon Microenvironment

Introduction: The successful integration of stem cells in adult brain has become a central issue in modern neuroscience. In this study we sought to test the hypothesis that survival and neurodifferentiation of mesenchymal stem cells (MSCs) may be dependent upon microenvironmental conditions according to the site of implant in the brain. Methods: MSCs were isolated from adult rats and labeled with enhanced-green fluorescent protein (eGFP) lentivirus. A cell suspension was implanted stereotactically into the brain of 50 young rats, into one neurogenic area (hippocampus), and into another nonneurogenic area (striatum). Animals were sacrificed 6 or 12 weeks after surgery, and brains were stained for mature neuronal markers. Cells coexpressing NeuN (neuronal specific nuclear protein) and GFP (green fluorescent protein) were counted stereologically at both targets. Results: The isolated cell population was able to generate neurons positive for microtubule-associated protein 2 (MAP2), neuronal-specific nuclear protein (NeuN), and neurofilament 200 (NF200) in vitro. Electrophysiology confirmed expression of voltage-gated ionic channels. Once implanted into the hippocampus, cells survived for up to 12 weeks, migrated away from the graft, and gave rise to mature neurons able to synthesize neurotransmitters. By contrast, massive cell degeneration was seen in the striatum, with no significant migration. Induction of neuronal differentiation with increased cyclic adenosine monophosphate in the culture medium before implantation favored differentiation in vivo. Conclusions: Our data demonstrated that survival and differentiation of MSCs is strongly dependent upon a permissive microenvironment. Identification of the pro-neurogenic factors present in the hippocampus could subsequently allow for the integration of stem cells into nonpermissive areas of the central nervous system.

Electrospray MS-based characterization of beta-carbolines - mutagenic constituents of thermally processed meat

The beta-carbolines 1-methyl-9H-pyrido [3,4-b]indole and 9H-pyrido[3,4b]indole have been implicated as having causative roles in a number of human diseases, such as Parkinson`s disease and cancer. As they can be formed during the heating of protein-rich food, a number of analytical methodologies have been proposed for their detection and quantification in foodstuff For this purpose, LC-MS and LC-MS/MS have emerged as the most specific analytical methods, and the quantification is based on the occurrence of unusual ions, such as [M+H-(H(center dot))](+) and [M + H-2H](+). In this study, we have investigated the formation of these ions by accurate-mass electrospray MS/MS and demonstrated that these ions are formed from gas-phase ion-molecule reactions between water vapor present in the collision cell and the protonated molecule of 1-methyl-9H-pyrido [3,4-b]indole and 9H-pyrido[3,4b]indole. Although this reaction has been previously described for heterocyclic amine ions, it has been overlooked in the most of recent LC-MS and LC-MS/MS studies, and no complete data of the fragmentation are reported. Our results demonstrate that additional attention should be given with respect to eliminating water vapor residues in the mass spectrometer when analysis of beta-carbolines is performed, as this residue may affect the reliability in the results of quantification.

Molecular dynamics, flexible docking, virtual screening, ADMET predictions, and molecular interaction field studies to design novel potential MAO-B inhibitors

Monoamine oxidase is a flavoenzyme bound to the mitochondrial outer membranes of the cells, which is responsible for the oxidative deamination of neurotransmitter and dietary amines. It has two distinct isozymic forms, designated MAO-A and MAO-B, each displaying different substrate and inhibitor specificities. They are the well-known targets for antidepressant, Parkinson`s disease, and neuroprotective drugs. Elucidation of the x-ray crystallographic structure of MAO-B has opened the way for the molecular modeling studies. In this work we have used molecular modeling, density functional theory with correlation, virtual screening, flexible docking, molecular dynamics, ADMET predictions, and molecular interaction field studies in order to design new molecules with potential higher selectivity and enzymatic inhibitory activity over MAO-B.

Redefining functional models of basal ganglia organisation: Role for the posteroventral pallidum in linguistic processing?

Traditionally the basal ganglia have been implicated in motor behavior, as they are involved in both the execution of automatic actions and the modification of ongoing actions in novel contexts. Corresponding to cognition, the role of the basal ganglia has not been defined as explicitly. Relative to linguistic processes, contemporary theories of subcortical participation in language have endorsed a role for the globus pallidus internus (GPi) in the control of lexical-semantic operations. However, attempts to empirically validate these postulates have been largely limited to neuropsychological investigations of verbal fluency abilities subsequent to pallidotomy. We evaluated the impact of bilateral posteroventral pallidotomy (BPVP) on language function across a range of general and high-level linguistic abilities, and validated/extended working theories of pallidal participation in language. Comprehensive linguistic profiles were compiled up to 1 month before and 3 months after BPVP in 6 subjects with Parkinson's disease (PD). Commensurate linguistic profiles were also gathered over a 3-month period for a nonsurgical control cohort of 16 subjects with PD and a group of 16 non-neurologically impaired controls (NC). Nonparametric between-groups comparisons were conducted and reliable change indices calculated, relative to baseline/3-month follow-up difference scores. Group-wise statistical comparisons between the three groups failed to reveal significant postoperative changes in language performance. Case-by-case data analysis relative to clinically consequential change indices revealed reliable alterations in performance across several language variables as a consequence of BPVP. These findings lend support to models of subcortical participation in language, which promote a role for the GPi in lexical-semantic manipulation mechanisms. Concomitant improvements and decrements in postoperative performance were interpreted within the context of additive and subtractive postlesional effects. Relative to parkinsonian cohorts, clinically reliable versus statistically significant changes on a case by case basis may provide the most accurate method of characterizing the way in which pathophysiologically divergent basal ganglia linguistic circuits respond to BPVP.

Morphosyntactic and syntactic priming: an investigation of underlying processing mechanisms and the effects of Parkinson’s disease

There is now considerable evidence to suggest that non-demented people with Parkinson's disease (PD) experience difficulties using the morphosyntactic aspects of language. It remains unclear, however, at precisely which point in the processing of morphosyntax, these difficulties emerge. The major objective of the present study was to examine the impact of PD on the processes involved in accessing morphosyntactic information in the lexicon. Nineteen people with PD and 19 matched control subjects participated in the study which employed on-line word recognition tasks to examine morphosyntactic priming for local grammatical dependencies that occur both within (e.g. is going) and across (e.g. she gives) phrasal boundaries (Experiments 1 and 2, respectively). The control group evidenced robust morphosyntactic priming effects that were consistent with the involvement of both pre- (Experiment 1) and post-lexical (Experiment 2) processing routines. Whilst the participants with PD also recorded priming for dependencies within phrasal boundaries (Experiment 1), priming effects were observed over an abnormally brief time course. Further, in contrast to the controls, the PD group failed to record morphosyntactic priming for constructions that crossed phrasal boundaries (Experiment 2). The results demonstrate that attentionally mediated mechanisms operating at both the pre- and post-lexical stages of processing are able to contribute to morphosyntactic priming effects. In addition, the findings support the notion that, whilst people with PD are able to access morphosyntactic information in a normal manner, the time frame in which this information remains available for processing is altered. Deficits may also be experienced at the post-lexical integrational stage of processing.

Test–retest repeatability of self-reported environmental exposures in Parkinson’s disease cases and healthy controls

There is substantial disagreement among published epidemiological studies regarding environmental risk factors for Parkinson’s disease (PD). Differences in the quality of measurement of environmental exposures may contribute to this variation. The current study examined the test–retest repeatability of self-report data on risk factors for PD obtained from a series of 32 PD cases recruited from neurology clinics and 29 healthy sex-, age-and residential suburb-matched controls. Exposure data were collected in face-to-face interviews using a structured questionnaire derived from previous epidemiological studies. High repeatability was demonstrated for ‘lifestyle’ exposures, such as smoking and coffee/tea consumption (kappas 0.70–1.00). Environmental exposures that involved some action by the person, such as pesticide application and use of solvents and metals, also showed high repeatability (kappas>0.78). Lower repeatability was seen for rural residency and bore water consumption (kappa 0.39–0.74). In general, we found that case and control participants provided similar rates of incongruent and missing responses for categorical and continuous occupational, domestic, lifestyle and medical exposures.

Prevalence of Parkinson’s disease in metropolitan and rural Queensland: A general practice survey

The prevalence of idiopathic Parkinson’s disease (IPD) in Australia is unclear. We estimated the prevalence of IPD, and other forms of parkinsonism, through the study of typical caseloads in general practice. A random sample of general practitioners (GPs) throughout Queensland (401 responses from 528 validated practice addresses) was asked to estimate the numbers of patients with IPD and parkinsonism seen in the preceding year. The estimated prevalence of diagnosed IPD in Queensland was 146 per 100 000 (95% CI = 136–155). A further 51 per 100 000 in the population were suspected by doctors to have IPD without formal diagnosis, whereas another 51 per 100 000 people may have non-idiopathic parkinsonism. Idiopathic Parkinson’s disease was more common in rural than metropolitan areas. Although most GPs were confident in making diagnoses of IPD, the majority had little or no confidence in their ability to treat the disease, especially in its later stages. Support from neurologists was perceived by GPs to be very good in cities, but poor in remote areas.

Sequence heterogeneity in Parkinsonian speech

Parkinson's disease (PD) is a neurodegenerative movement disorder primarily due to basal ganglia dysfunction. While much research has been conducted on Parkinsonian deficits in the traditional arena of musculoskeletal limb movement, research in other functional motor tasks is lacking. The present study examined articulation in PD with increasingly complex sequences of articulatory movement. Of interest was whether dysfunction would affect articulation in the same manner as in limb-movement impairment. In particular, since very Similar (homogeneous) articulatory sequences (the tongue twister effect) are more difficult for healthy individuals to achieve than dissimilar (heterogeneous) gestures, while the reverse may apply for skeletal movements in PD, we asked which factor would dominate when PD patients articulated various grades of artificial tongue twisters: the influence of disease or a possible difference between the two motor systems. Execution was especially impaired when articulation involved a sequence of motor program heterogeneous in terms of place of articulation. The results are suggestive of a hypokinesic tendency in complex sequential articulatory movement as in limb movement. It appears that PD patients do show abnormalities in articulatory movement which are similar to those of the musculoskeletal system. The present study suggests that an underlying disease effect modulates movement impairment across different functional motor systems. (C) 1998 Academic Press.