Aim: Post-exertional malaise (PEM) has been a challenging construct to measure, particularly with self-report instruments, which have the benefits of being less expensive and less invasive than cardiopulmonary exercise tests. Existing PEM questionnaires have often been used for diagnostic purposes and less frequently as outcome measures. Few self-report PEM measures address comprehensive PEM domains, including types of triggers, duration of symptoms, delayed symptom onset, number of symptoms, frequency and severity of symptoms, as well as whether pacing or other strategies reduce or eliminate PEM. Without characterizing these features, salient aspects of PEM would be overlooked. However, efforts to assess all these domains can be time-consuming and potentially burdensome. Methods: The current study offers investigators a brief but comprehensive instrument of critical PEM domains, called the DePaul Symptom Questionnaire (DSQ)-PEM-2, to assess PEM. Validation data were derived from a large sample of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Results: The DSQ-PEM-2 was developed using an existing dataset of individuals with ME, CFS, or both ME and CFS, allowing comprehensive coverage of key PEM domains. Conclusions: The DSQ-PEM-2 can be used either for diagnostic purposes or as an outcome measure. The instrument’s time frames for symptom manifestation can be adapted to suit a variety of research or clinical contexts. Future validation studies need to include a healthy control group.

Degeneration and dysfunction of neurons in the brain are hallmarks of neurodegenerative diseases. Over the past decades, significant efforts have been devoted to the development and validation of biomarkers for neurodegenerative diseases. The range and diversity of biomarkers for central nervous system (CNS) diseases has continued to expand, encompassing biofluid-based sources such as blood or cerebrospinal fluid (CSF), nucleic acids, tissues, and imaging. While imaging and tissue biopsy-based markers are continually being identified and their applications expanding, they do have limitations compared with RNA and protein biomarkers. This review comprehensively summarizes various biomarkers, including microRNA (miRNA), long noncoding RNA (lncRNA), circulating miRNA (cimiRNA), and proteins, in the context of CNS disorders. In addition, the review emphasizes the existing limitations and challenges associated with the use of biomarkers in both clinical practice and research on neurodegenerative diseases. In conclusion, this review provides an insightful overview of the identified biomarkers for neurodegenerative diseases, underscoring the crucial role of biomarker research in combating these debilitating conditions. The article also highlights future challenges related to the implementation of novel biomarkers in clinical practice and trials, thereby contributing to the ongoing efforts to advance the understanding and management of neurodegenerative diseases.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting 1% of the population above sixty years. It is caused by an interaction between genetic and environmental risk factors. Loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) is pathologically characterizing the disease and responsible for the cardinal motor symptoms, most notably, bradykinesia, rest tremors, rigidity, and loss of postural reflexes. Non-motor signs such as olfactory deficits, cognitive impairment, sleep behavior disorders, and gastrointestinal disturbances are reflecting disturbances in the non-dopaminergic system. They precede dopaminergic neuronal degenerations by 5–10 years and are considered the main contributors to patients’ disability, particularly after the successful implementation of levodopa (L-dopa) treatment of motor symptoms. The present general review aimed to briefly update non-motor signs and their underlying pathophysiology in PD.