Publications by authors named "Joseph ClaSSen"

Introduction: Modifiable risk factors play an important role in preventing dementia and reducing its progression. Regular physical activity already in midlife, which relies on intact multisensory balance control, can help to decrease the risk of dementia. However, our understanding of the relationship between postural balance and cognitive functions remains limited.

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Successful motor skill acquisition requires the dynamic interaction of multiple brain regions, with the striatum playing a critical role in this network. Animal studies suggest that dopaminergic mechanisms are involved in the regulation of motor learning-associated striatal plasticity. In humans, however, the contribution of nigrostriatal dopaminergic transmission to motor learning remains elusive beyond its well-characterized role in initiation and fluent execution of movements.

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Background And Objective: There are multiple pharmacological treatment options for motor symptoms of Parkinson's disease (PD). These comprise multiple drug classes which are approved for the condition, including levodopa, dopamine agonists, COMT inhibitors, MAO-B inhibitors, NMDA-receptor antagonists, anticholinergics, and others. Some of the drugs are approved for monotherapy and combination therapy while others are only approved as adjunctive therapy to levodopa.

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Disease-modifying therapeutics in the α-synucleinopathies multiple system atrophy (MSA) and Parkinson's Disease (PD) are in early phases of clinical testing. Involving patients' preferences including therapy-associated risk willingness in initial stages of therapy development has been increasingly pursued in regulatory approval processes. In our study with 49 MSA and 38 PD patients, therapy-associated risk willingness was quantified using validated standard gamble scenarios for varying severities of potential drug or surgical side effects.

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Article Synopsis
  • Current estimates of genetic variants linked to Parkinson's disease (PD) show limitations and biases across different populations, complicating patient recruitment for clinical trials focused on genetic therapies.
  • The Rostock Parkinson's disease (ROPAD) study analyzes data from 12,580 PD patients across 16 countries, revealing that 14.8% had a genetic test positive for PD-related variants, particularly in specific genes like GBA1 and LRRK2.
  • Findings indicate higher positivity rates in patients with earlier onset (age ≤ 50) or a positive family history, emphasizing the need for more extensive genetic investigation to improve patient stratification for future clinical trials.
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  • The study aimed to create a shorter version of the Progressive Supranuclear Palsy quality of life scale (PSP-QoL) to make it easier for patients, especially those with cognitive impairments, to complete.
  • Involved a retrospective analysis of data from 245 PSP patients in Germany, resulting in a condensed 12-item scale that covers mental and physical aspects of daily living.
  • The new scale, called the PSP-ShoQoL, showed strong correlations with existing measures of quality of life and demonstrated its sensitivity to changes over time.
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Tremor, whether arising from neurological diseases, other conditions, or medication side effects, significantly impacts patients' lives. Treatment complexities necessitate clear algorithms and strategies. Levodopa remains pivotal for Parkinson's tremor, though response variability exists.

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Background: Abnormal expansion of the echogenic substantia nigra (SN+) is a common observation in Parkinson's disease (PD) and considered a potential trait marker within this context. However, SN+ was also frequently detected in children diagnosed with attention-deficit/hyperactivity disorder (ADHD), where it has been discussed as a biomarker of maturational dopaminergic dysfunction. Interestingly, ADHD was recently linked to an elevated risk of PD in epidemiological studies, particularly among individuals treated with psychostimulants.

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Introduction: Frontotemporal lobar degeneration (FTLD) encompasses behavioral variant frontotemporal dementia (bvFTD), progressive supranuclear palsy, corticobasal syndrome/degeneration, and primary progressive aphasias (PPAs). We cross-validated fluid biomarkers and neuroimaging.

Methods: Seven fluid biomarkers from cerebrospinal fluid and serum were related to atrophy in 428 participants including these FTLD subtypes, logopenic variant PPA (lvPPA), Alzheimer's disease (AD), and healthy subjects.

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Purpose: We hypothesized that severe tau burden in brain regions involved in direct or indirect pathways of the basal ganglia correlate with more severe striatal dopamine deficiency in four-repeat (4R) tauopathies. Therefore, we correlated [F]PI-2620 tau-positron-emission-tomography (PET) imaging with [I]-Ioflupane single-photon-emission-computed tomography (SPECT) for dopamine transporter (DaT) availability.

Methods: Thirty-eight patients with clinically diagnosed 4R-tauopathies (21 male; 69.

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  • - The study investigated stroke survivors' preferences regarding patient-reported outcome measures (PROMs) to assess their quality of life and unmet needs, highlighting their perspectives on the assessment process.
  • - A paper-based questionnaire was distributed to stroke patients in Germany, revealing that most participants were open to PROMs, believing they could enhance care for themselves and others, with a preference for annual interviews and written surveys lasting 15-30 minutes.
  • - Findings suggest that personalized approaches to administering PROMs, including the preferred communication methods and timing, could better implement these assessments in clinical practice and improve stroke care outcomes.
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  • Progressive supranuclear palsy (PSP) patients, typically older adults, have a distinct pattern of health comorbidities and often take multiple medications compared to those without neurodegenerative diseases.
  • The study analyzed data from over 600 patients, revealing higher rates of circulatory and nervous system diseases in PSP patients, alongside increased occurrences of conditions like diabetes and polyneuropathies.
  • The PSP group showed significantly more polypharmacy, leading to a higher risk of severe drug interactions, highlighting the need for careful management of treatment in these patients.
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CSF1 receptor-related leukoencephalopathy is a rare genetic disorder presenting with severe, adult-onset white matter dementia as one of the leading symptoms. Within the central nervous system, the affected CSF1-receptor is expressed exclusively in microglia cells. Growing evidence implicates that replacing the defective microglia with healthy donor cells through hematopoietic stem cell transplant might halt disease progression.

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Objective: Phenylketonuria (PKU) is a rare inherited metabolic disorder characterised by elevated phenylalanine (Phe) concentrations that can exert neurotoxic effects if untreated or upon treatment discontinuation. This systematic review supported by expert opinion aims to raise awareness among the neurological community on neurological complications experienced by adults with PKU (AwPKU).

Methods: The PubMed database was searched for articles on neurological signs and symptoms in AwPKU published before March 2022.

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The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists.

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Motor learning is defined as an improvement in performance through practice. The ability to learn new motor skills may be particularly challenged in patients with Parkinson's disease, in whom motor execution is impaired by the disease-defining motor symptoms such as bradykinesia. Subthalamic deep brain stimulation is an effective treatment in advanced Parkinson's disease, and its beneficial effects on Parkinsonian motor symptoms and motor execution have been widely demonstrated.

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By understanding stroke as a chronic disease, aftercare becomes increasingly important. For developing aftercare programs, the patients' perspective regarding, for example, stroke-related symptoms and interactions with the healthcare system is necessary. Records from a local stroke pilot program were used to extract relevant topics from the patients' perspective, as mentioned during a phone call two months after hospital discharge.

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Patients with Post-COVID syndrome (PCS) are frequently referred for cardiologic evaluation. We assessed cardiac function and biomarkers in relation to functional status and fatigue in patients with PCS. This prospective single-center cohort study included 227 patients with persisting symptoms after COVID-19 infection.

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Background: In the treatment of status epilepticus less is known about the influence of comorbidities on the safety profile of anticonvulsive drugs. Especially patients with diabetes mellitus may be predisposed to certain adverse events that have been related to therapy with valproic acid. In this single-center retrospective cohort study we examined if the complications of the intravenous treatment with valproic acid is different in patients with or without diabetes.

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The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021.

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Purpose: Early after [F]PI-2620 PET tracer administration, perfusion imaging has potential for regional assessment of neuronal injury in neurodegenerative diseases. This is while standard late-phase [F]PI-2620 tau-PET is able to discriminate the 4-repeat tauopathies progressive supranuclear palsy and corticobasal syndrome (4RTs) from disease controls and healthy controls. Here, we investigated whether early-phase [F]PI-2620 PET has an additive value for biomarker based evaluation of 4RTs.

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Essential tremor (ET) is a progressive movement disorder whose pathophysiology is not fully understood. Current evidence supports the view that the cerebellum is critically involved in the genesis of the tremor in ET. However, it is still unknown whether cerebellar dysfunction affects not only the control of current movements but also the prediction of future movements through dynamic adaptation toward a changed environment.

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Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization.

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Background: Alzheimer's disease and depression can start with combined cognitive and depressive symptoms [1, 2]. Accurate differential diagnosis is desired to initiate specific treatment.

Objective: We investigated whether amyloid-β PET imaging can discriminate both entities.

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Bradykinesia is a cardinal motor symptom in Parkinson's disease (PD), the pathophysiology of which is not fully understood. We analyzed the role of cross-frequency coupling of oscillatory cortical activity in motor impairment in patients with PD and healthy controls. High-density EEG signals were recorded during various motor activities and at rest.

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