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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
61

Adaptive changes in striatal projection neurons explain the long duration response and the emergence of dyskinesias in patients with Parkinson’s disease: Neurology and Preclinical Neurological Studies - Review Article

Falkenburger, Björn, Kalliakoudas, Theodoros, Reichmann, Heinz 22 March 2024 (has links)
Neuronal activity in the brain is tightly regulated. During operation in real time, for instance, feedback and feedforward loops limit excessive excitation. In addition, cell autonomous processes ensure that neurons’ average activity is restored to a setpoint in response to chronic perturbations. These processes are summarized as homeostatic plasticity (Turrigiano in Cold Spring Harb Perspect Biol 4:a005736–a005736, 2012). In the basal ganglia, information is mainly transmitted through disinhibition, which already constraints the possible range of neuronal activity. When this tightly adjusted system is challenged by the chronic decline in dopaminergic neurotransmission in Parkinson’s disease (PD), homeostatic plasticity aims to compensate for this perturbation. We here summarize recent experimental work from animals demonstrating that striatal projection neurons adapt excitability and morphology in response to chronic dopamine depletion and substitution. We relate these cellular processes to clinical observations in patients with PD that cannot be explained by the classical model of basal ganglia function. These include the long duration response to dopaminergic medication that takes weeks to develop and days to wear off. Moreover, dyskinesias are considered signs of excessive dopaminergic neurotransmission in Parkinson’s disease, but they are typically more severe on the body side that is more strongly affected by dopamine depletion. We hypothesize that these clinical observations can be explained by homeostatic plasticity in the basal ganglia, suggesting that plastic changes in response to chronic dopamine depletion and substitution need to be incorporated into models of basal ganglia function. In addition, better understanding the molecular mechanism of homeostatic plasticity might offer new treatment options to avoid motor complications in patients with PD.
62

Development and Validation of a Fall Questionnaire for Patients with Parkinson’s Disease

Frank, Anika, Bendig, Jonas, Finkbeiner, Sophia, Hähnel, Tom, Schnalke, Nils, Feige, Tim, Reichmann, Heinz, Falkenburger, Björn H. 04 April 2024 (has links)
Abstract: Background: In Parkinson’s disease, postural instability and falls are of particular socioeconomic relevance. Although effective fall prevention and the prophylaxis of fall-related injuries depend on low-threshold symptom monitoring, validated instruments are lacking. Objectives: To develop a self-report questionnaire for the assessment of falls, near falls, fear of falling, fallrelated injuries, and causes of falls for patients with Parkinson’s disease (PwPD). - Methods: A pool of potential items was generated from a literature review and by discussion in an expert panel. The first version of the Dresden Fall Questionnaire (DREFAQ) was tested in a group of German-speaking movement disorder specialists as well as PwPD. The resulting 5-item questionnaire was assessed in a validation cohort of 36 PwPD who documented fall events and near-fall events in a calendar for 3 months and completed the DREFAQ at the end of the study. The questionnaire was subsequently used in a separate cohort of 46 PwPD to determine test–retest reliability and confirm the factor structure. - Results: The DREFAQ showed good internal consistency (Cronbach’s α = 0.84) and good test–retest reliability (intraclass correlation coefficient, 0.76; 95% confidence interval, 0.60–0.86). The total DREFAQ score showed good concurrent validity with fall events (Spearman’s ρ = 0.82) and near-fall events (Spearman’s ρ = 0.78) as determined by fall and near-fall diaries. Factor analysis revealed a 2-factor structure composed of near falls with fear of falling and severe falls with injuries. - Conclusions: The DREFAQ is a reliable and valid 5-item questionnaire for determining the incidence of falls, near falls, fear of falling, fall-related injuries, and causes of falls in PwPD.
63

Opicapone Use in Clinical Practice across Germany: A Sub-Analysis of the OPTIPARK Study in Parkinson’s Disease Patients with Motor Fluctuations

Reichmann, Heinz, Eggert, Karla, Oehlwein, Christian, Warnecke, Tobias, Lees, Andrew J., Kemmer, Michael, Soares-da-Silva, Patrício 21 May 2024 (has links)
Introduction: The OPTIPARK study confirmed the effectiveness and safety of opicapone as adjunct therapy to levodopa in patients with Parkinson’s disease (PD) and motor fluctuations under real-world conditions. The aim of this sub-analysis was to evaluate opicapone in the German patient cohort of OPTIPARK in order to provide country-specific data. Methods: OPTIPARK was an open-label, single-arm study conducted in routine clinical practice across Germany and the UK. Patients with PD and motor fluctuations received once-daily opicapone 50 mg for 3 months in addition to levodopa. The primary endpoint was Clinicians’ Global Impression of Change (CGI-C). Secondary assessments included Patients’ Global Impressions of Change (PGI-C), Unified Parkinson’s Disease Rating Scale (UPDRS) I–IV, Parkinson’s Disease Questionnaire (PDQ-8), and Non-Motor Symptoms Scale (NMSS). This sub-analysis reports outcomes from the German patients only. Results: Overall, 363 (97.6%) of the 372 patients included in the German cohort received ≥1 dose of opicapone and 291 (80.2%) completed the study. Improvements on CGI-C and PGI-C were reported by 70.8% and 76.3% of patients, respectively. UPDRS scores improved for activities of daily living during OFF time by −3.3 ± 4.5 points and motor scores during ON time by −5.3 ± 7.9 points. PDQ-8 and NMSS scores also demonstrated improvements. Treatment emergent adverse events considered at least possibly related to opicapone occurred in 37.7% of patients, with most being of mild or moderate intensity. Conclusion: Opicapone added to levodopa in patients with PD and motor fluctuations was effective and generally well tolerated in routine clinical practice across Germany.
64

Möglichkeiten und Grenzen bewegungstherapeutischer Intervention bei Parkinsonpatienten

Augustijn, Julia 12 November 2012 (has links) (PDF)
Die posturale Instabilität zählt zu den am meisten beeinträchtigenden Symptomen der Parkinson-Krankheit. Die Störung der motorischen Gleichgewichtskontrolle ist progressiv im Verlauf und weder durch medikamentöse noch durch operative Methoden zufriedenstellend einzudämmen. In der Bewegungstherapie werden häufig Gleichgewichtsübungen empfohlen, um ein Fortschreiten der körperlichen Einschränkungen zu verringern. Der aktuelle wissenschaftliche Stand lässt allerdings eine Einschätzung zur Effektivität von Gleichgewichtstraining bei Parkinsonpatienten kaum zu. Dies ist u. a. auf einen Mangel an geeigneten Testverfahren zur Beurteilung der posturalen Instabilität zurückzuführen. In der vorliegenden Untersuchung wurden die Auswirkungen eines 12-wöchigen Gleichgewichtstrainings bei Parkinsonpatienten auf die posturale Stabilität in einem umfassenden Testdesign, bestehend aus alltagsmotorischen, biomechanischen und subjektiven Testverfahren evaluiert. In nahezu allen eingesetzten Testverfahren zeigte sich ein mehr oder weniger deutlicher Trend zu einer Verbesserung der posturalen Stabilität. Durch den Einsatz einer Testbatterie konnte somit insgesamt von einem positiven Einfluss eines Gleichgewichtstrainings auf die posturale Stabilität von Parkinsonpatienten ausgegangen werden. Weiterhin werden zahlreiche positive Nebeneffekte bzgl. der allgemeinen Fitness, der psychischen und sozialen Situation durch ein zielgerichtetes Gruppentraining unter geschulter Anleitung vermutet.
65

Mitochondriale DNA Mutationen und Untersuchungen zum oxidativen Stress beim idiopathischen Parkinsonsyndrom

Sonnenschein, Anka 12 October 2006 (has links) (PDF)
Bis heute ist die Ätiopathogenese der Parkinson Krankheit noch nicht geklärt. Verschiedene Abweichungen im Stoffwechsel von Betroffenen konnten zwar detektiert werden (z.B. Komplex I-Mangel, erhöhte Eisen- und 8-OHdG Werte im Gehirn), aber bis heute gibt es keine eindeutigen Hinweise, wodurch es zur Entstehung der Krankheit kommt. Da es am wahrscheinlichsten ist, dass die Krankheit multifaktoriell bedingt ist, könnten auch Mutationen der mitochondrialen DNA eine wichtige Rolle spielen. Entscheidende Hinweise darauf lieferten Experimente mit Cybrid–Zellen. Bisherige Screeninguntersuchungen des mitochondrialen Genoms konnten allerdings noch keine eindeutigen krankheitsspezifischen Mutationen nachweisen. Die Theorie, dass oxidativer Stress in Verbindung mit der Parkinsonschen Krankheit stehen könnte, fand Unterstützung, als signifikant erhöhte Produkte der Lipidperoxidation (Malondialdehyd, Lipidhydroperoide) in der Substantia nigra (Dexter et al., 1989 b, 1994) und ein abnormaler Eisenstoffwechsel in den Basalganglien des Gehirns (Dexter et al., 1987; Dexter et al., 1989a; Cadet, 2001; Hirsch et al., 1991) einiger Patienten nachgewiesen worden. Erhöhte Eisenwerte in Neuromelaninaggregationen, sowie verringerte Ferritinspiegel unterstützen diese Untersuchungen (Cadet, 2001; Dexter et al., 1987, 1989b; Riederer et al., 1989; Sofic et al., 1988). Besonders anfällig für reaktive Sauerstoffverbindungen im Gehirn ist die Substantia nigra. Zum einen kommt es während des Dopaminstoffwechsels zur Freisetzung von Wasserstoffperoxid, des weiteren enthält sie Neuromelanin, welches selektiv Metalle (z.B. Eisen) bindet. Reduziertes Eisen kann mit Wasserstoffperoxid via Fentonreaktion reagieren und das äußerst schädliche Hydroxylradikal bilden (Klein & Ackerman, 2003). Die Menge der in den Mitochondrien frei werdenden Radikale ist von einer Reihe von verschiedenen Faktoren abhängig. Umwelteinflüsse und Ernährungsfaktoren spielen dabei eine ebenso wichtige Rolle, wie der mitochondriale Stoffwechsel selbst (Adachi et al., 1993; Simic, 1991; Menegon et al., 1997). Als ein Biomarker für den oxidativen Stress hat sich in den letzten Jahren 8-Hydroxy-2’-deoxyguanosin (8-OHdG) etabliert, welches als Folge von Angriffen des Hydroxyl-Radikals auf die Doppelbindungen der DNA-Basen am häufigsten gebildet wird (Simic, 1991; Dizdaroglu et al., 1991, Kasai, 1997). 8-OHdG ist in der Lage sich mit Adenin zu paaren (ca. 1% der Fälle), was wiederum bei der nächsten Replikation zu einer Transversion von Guanin zu Thymin führt (Richter, 1992; Croteau & Bohr, 1997).
66

The Saccharomyces cerevisiae HtrA orthologue, Ynm3, is a chaperone-protease that aids survival under heat stress / Das Saccharomyces cerevisiae HtrA Ortholog, Ynm3, ist eine Chaperon-Protease, die für das Überleben unter Hitzestress verantwortlich ist

Padmanabhan, Nirmala 03 November 2008 (has links)
No description available.
67

Should Skin Biopsies Be Performed in Patients Suspected of Having Parkinson’s Disease?

Siepmann, Timo, Penzlin, Ana Isabel, Illigens, Ben Min-Woo, Reichmann, Heinz 06 June 2018 (has links) (PDF)
In patients with Parkinson’s disease (PD), the molecularly misfolded form of α-synuclein was recently identified in cutaneous autonomic nerve fibers which displayed increased accumulation even in early disease stages. However, the underlying mechanisms of synucleinopathic nerve damage and its implication for brain pathology in later life remain to be elucidated. To date, specific diagnostic tools to evaluate small fiber pathology and to discriminate neurodegenerative proteinopathies are rare. Recently, research has indicated that deposition of α-synuclein in cutaneous nerve fibers quantified via immunohistochemistry in superficial skin biopsies might be a valid marker of PD which could facilitate early diagnosis and monitoring of disease progression. However, lack of standardization of techniques to quantify neural α-synuclein deposition limits their utility in clinical practice. Additional challenges include the identification of potential distinct morphological patterns of intraneural α-synuclein deposition among synucleinopathies to facilitate diagnostic discrimination and determining the degree to which structural damage relates to dysfunction of nerve fibers targeted by α-synuclein. Answering these questions might improve our understanding of the pathophysiological role of small fiber neuropathy in Parkinson’s disease, help identify new treatment targets, and facilitate assessment of response to neuroprotective treatment.
68

Should Skin Biopsies Be Performed in Patients Suspected of Having Parkinson’s Disease?

Siepmann, Timo, Penzlin, Ana Isabel, Illigens, Ben Min-Woo, Reichmann, Heinz 06 June 2018 (has links)
In patients with Parkinson’s disease (PD), the molecularly misfolded form of α-synuclein was recently identified in cutaneous autonomic nerve fibers which displayed increased accumulation even in early disease stages. However, the underlying mechanisms of synucleinopathic nerve damage and its implication for brain pathology in later life remain to be elucidated. To date, specific diagnostic tools to evaluate small fiber pathology and to discriminate neurodegenerative proteinopathies are rare. Recently, research has indicated that deposition of α-synuclein in cutaneous nerve fibers quantified via immunohistochemistry in superficial skin biopsies might be a valid marker of PD which could facilitate early diagnosis and monitoring of disease progression. However, lack of standardization of techniques to quantify neural α-synuclein deposition limits their utility in clinical practice. Additional challenges include the identification of potential distinct morphological patterns of intraneural α-synuclein deposition among synucleinopathies to facilitate diagnostic discrimination and determining the degree to which structural damage relates to dysfunction of nerve fibers targeted by α-synuclein. Answering these questions might improve our understanding of the pathophysiological role of small fiber neuropathy in Parkinson’s disease, help identify new treatment targets, and facilitate assessment of response to neuroprotective treatment.
69

Cutaneous Autonomic Pilomotor Testing to Unveil the Role of Neuropathy Progression in Early Parkinson’s Disease (CAPTURE PD): Protocol for a Multicenter Study

Siepmann, Timo, Pintér, Alexandra, Buchmann, Sylvia J., Stibal, Leonie, Arndt, Martin, Kubasch, Anne Sophie, Kubasch, Marie Luise, Penzlin, Ana Isabel, Frenz, Elka, Zago, Wagner, Horváth, Tamás, Szatmári Jr., Szabolcs, Bereczki, Dániel, Takáts, Annamária, Ziemssen, Tjalf, Lipp, Axel, Freeman, Roy, Reichmann, Heinz, Barlinn, Kristian, Illigens, Ben Min-Woo 10 November 2017 (has links)
Background: In Parkinson’s disease (PD), alpha-synuclein accumulation in cutaneous autonomic pilomotor and sudomotor nerve fibers has been linked to autonomic nervous system disturbances even in the early stages of the disease. This study aims to assess the association between alpha-synuclein-mediated structural autonomic nerve fiber damage and function in PD, elucidate the role of neuropathy progression during the early disease stages, and test reproducibility and external validity of pilomotor function assessment using quantitative pilomotor axon-reflex test and sudomotor function via quantitative direct and indirect test of sudomotor function. Methods/design: A prospective controlled study will be conducted at four study sites in Europe and the USA. Fifty-two male and female patients with idiopathic PD (Hoehn and Yahr 1–2) and 52 age- and sex-matched healthy controls will be recruited. Axon-reflex-mediated pilomotor erection will be induced by iontophoresis of phenylephrine on the dorsal forearm. Silicone impressions of the response will be obtained, scanned, and quantified for pilomotor muscle impressions by number, impression size, and area of axon-reflex spread. Axon-reflex-mediated sweating following acetylcholine iontophoresis will be quantified for number and size of droplets and axon-reflex spread. Sympathetic skin responses, autonomic and motor symptoms will be evaluated. Tests will be performed at baseline, after 2 weeks, 1, 2, and 3 years. Skin biopsies will be obtained at baseline and after 3 years and will be analyzed for nerve fiber density and alpha-synuclein accumulation. Discussion: We anticipate that progression of autonomic nerve dysfunction assessed via pilomotor and sudomotor axon-reflex tests is related to progression of autonomic symptom severity and alpha-synuclein deposition. Potential applications of the techniques include interventional studies evaluating disease-modifying approaches and clinical assessment of autonomic dysfunction in patients with PD.
70

Serum neurofilament indicates that DBS surgery can cause neuronal damage whereas stimulation itself does not

Frank, Anika, Bendig, Jonas, Schniewind, Iñaki, Polanski, Witold H., Sobottka, Stephan B., Reichmann, Heinz, Akgün, Katja, Ziemssen, Tjalf, Klingelhoefer, Lisa, Falkenburger, Björn H. 04 April 2024 (has links)
Deep brain stimulation (DBS) is a potent symptomatic therapy for Parkinson’s disease, but it is debated whether it causes or prevents neurodegeneration. We used serum neurofilament light chain (NFL) as a reporter for neuronal damage and found no difference between 92 patients with chronic STN-DBS and 57 patients on best medical treatment. Serum NFL transiently increased after DBS surgery whereas the initiation of STN stimulation did not affect NFL levels, suggesting that DBS surgery can be associated with neuronal damage whereas stimulation itself is not.

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