Non-motor symptoms (NMSs) of Parkinson’s disease (PD) were recognized by James Parkinson himself about 200 years ago and are now considered to be an integral part of PD, significantly contributing to the deterioration of patients’ quality of life. Although awareness of NMSs is growing, and several scientific societies now have dedicated non-motor study groups, the NMS burden is still the hidden face of PD and in most cases, clinicians’ views are focused on the motor symptoms alone. The literature was reviewed using several databases and scientific journals; this review provides a comprehensive description of the most common NMSs in PD, their clinical phenotype, social impact, diagnosis, and therapeutic management. Early recognition of these features may lead to more prompt and effective treatment and may help to better understand patients’ needs.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor-evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation-evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.

Lateral trunk flexion (LTF) and its severe form, called Pisa syndrome (PS), are highly invalidating axial postural abnormalities associated with Parkinson’s disease (PD). Management strategies for LTF lack strong scientific evidence. We present a real-life, longitudinal study evaluating long-term efficacy of botulinum toxin (BoNT) injections in axial muscles to reduce LTF and PS in PD. A total of 13 PD patients with LTF > 5° received ultrasound- and electromyography-guided BoNT injections every 4 months. Seven untreated matched PD patients with LTF served as controls and their changes in posture after 18 months were compared with those of seven patients continuing BoNT over 12 months. 53.8% of patients continued the BoNT injections for at least 12 months. Various individual LTF responses were observed. Overall, BoNT-treated patients obtained a not statistically significant improvement of LTF of 17 ± 41% (p = 0.237). In comparison, the seven untreated PD patients suffered a deterioration in LTF over 12 months by 36 ± 45% (p = 0.116), showing a significantly different trajectory of posture change (p = 0.026). In conclusion, repeated BoNT injections in axial muscles showed varying effects in managing PD-associated LTF, suggesting that: (a) a relevant number of patients with LTF can benefit from BoNT; (b) long-term treatment could prevent LTF worsening; (c) an instrumented, personalized approach is important; and (d) there is a need for prospective, long-term studies.

Botulinum toxin (BoNT) is an effective and safe therapy for the symptomatic treatment of several neurological disturbances. An important line of research has provided numerous pieces of evidence about the mechanisms of action of BoNT in the central nervous system, especially in the context of dystonia and spasticity. However, only a few studies focused on the possible central effects of BoNT in Parkinson’s disease (PD). We performed a systematic review to describe and discuss the evidence from studies focused on possible central effects of BoNT in PD animal models and PD patients. To this aim, a literature search in PubMed and SCOPUS was performed in May 2023. The records were screened according to title and abstract by two independent reviewers and relevant articles were selected for full-text review. Most of the papers highlighted by our review report that the intrastriatal administration of BoNT, through local anticholinergic action and the remodulation of striatal compensatory mechanisms secondary to dopaminergic denervation, induces an improvement in motor and non-motor symptoms in the absence of neuronal loss in animal models of PD. In human subjects, the data are scarce: a single neurophysiological study in tremulous PD patients found that the change in tremor severity after peripheral BoNT administration was associated with improved sensory–motor integration and intracortical inhibition measures. Further clinical, neurophysiological, and neuroimaging studies are necessary to clarify the possible central effects of BoNT in PD.

Non-motor symptoms (NMS) of Parkinson's disease (PD) were recognized by James Parkinson himself about 200 years ago and are now considered to be an integral part of PD, significantly contributing to the worse of patients’ quality of life. Although awareness of NMS is growing, and several scientific societies have now dedicated non-motor study groups, the NMS burden is still the hidden face of PD and in most cases the clinicians’ views are focused on the motor symptoms alone. Literature research has been performed using several databases and scientific journals; this review provides a comprehensive description of the most common NMS in PD, their clinical phenotype, social impact, diagnosis, and therapeutic management. Early recognition of these features may lead to more prompt and effective treatment and may help to better understand patients’ needs.

Paired associative stimulation (PAS) is a non-invasive brain stimulation technique that modulates synaptic plasticity in the human motor cortex (M1). Since previous studies have primarily used motor evoked potentials (MEPs) as outcome measure, cortical correlates of PAS-induced plasticity remain unknown. Therefore, the aim of this observational study was to investigate cortical correlates of a standard PAS induced plasticity in the primary motor cortex by using a combined TMS-EEG approach in a cohort of eighteen healthy subjects. In addition to the expected long-lasting facilitatory modulation of MEPs amplitude, PAS intervention also induced a significant increase in transcranial magnetic stimulation evoked potentials (TEPs) P30 and P60 amplitude. No significant correlation between the magnitude of PAS-induced changes in TEP components and MEP amplitude were observed. However, the linear regression analysis revealed that the combined changes in P30 and P60 component amplitudes significantly predicted the MEP facilitation after PAS. The findings of our study offer novel insight into the neurophysiological changes associated with PAS-induced plasticity at M1 cortical level and suggest a complex relationship between TEPs and MEPs changes following PAS.