37 research outputs found
Motor and non-motor symptoms in advanced Parkinson’s disease: current insights and future directions
Advanced Parkinson’s disease (PD) is characterized by significant motor and non-motor
complications, including levodopa-resistant symptoms such as freezing of gait (FoG), postural
instability, and dysphagia, alongside autonomic dysfunction. As the disease progresses, managing
these symptoms becomes increasingly complex. This thesis explores the role of advanced therapies,
including levodopa-carbidopa intestinal gel (LCIG) and deep brain stimulation (DBS), in addressing
some disabling symptoms such as postural abnormalities, freezing of gait (Fog), speech disturbance,
and some nonmotor symptoms such as dysautonomic disturbance and pain. Additionally, it
investigates the role of monoamine oxidase type B (MAO-B) inhibitors in managing both motor
and cognitive fluctuations in advanced PD. Integrating wearable sensor technologies allows
continuous monitoring of motor complications such as dyskinesias and FoG daily, offering a novel
approach to individualized treatment. This thesis stresses the demand for a multidisciplinary,
patient-centered approach to managing advanced PD, with particular attention to autonomic
dysfunctions and axial symptoms, potentially aided by using wearable sensors to obtain an objective
measurement to improve the patient’s quality of life
Levodopa/carbidopa intestinal gel via percutaneous endoscopic transgastric jejunostomy in advanced Parkinson's disease: hitting two birds with one stone?
: Here we focus on people with advanced PD undergoing percutaneous endoscopic transgastric jejunostomy (PEG-J) ("one stone") for LCIG infusion therapy for managing severe motor fluctuations ("first bird") and discuss its implications for improving accompanying symptoms of cardiovascular, urinary, and gastrointestinal autonomic failure ("second bird")
Magnetically controlled growing rods for early scoliosis treatment in coffin-siris syndrome. Case report and literature review
Coffin-Siris Syndrome (CSS) is a rare, genetic syndrome characterized by multiple anomalies, including scoliosis. However, there are only a few reports about the management of scoliosis in these patients. We present the case of an 8-year-old female with CSS presenting with a progressive, rigid thoracolumbar kyphoscoliosis. She was successfully treated with a magnetically controlled growing rod, demonstrating improved ambulatory capacity and performance of activities of daily living. In pediatric patients with Coffin-Siris syndrome, magnetic expandable rods can be considered as an option for the management of progressive early-onset scoliosis. Level of Evidence: V
Levodopa/carbidopa intestinal gel for pain related to levodopa-induced motor complications in Parkinson’s disease
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Monoamine-Oxidase type B- Inhibitors and Cognitive Functions in Parkinson's Disease: Beyond the Primary Mechanism of Action
Symptoms of cognitive impairment are rather common since the early stage of Parkinson's disease (PD), aggravate with disease progression and may lead to dementia in a significant proportion of cases. Worsening of cognitive symptoms in PD patients depends on the progression of subcortical dopaminergic damage as well as the involvement of other brain neurotransmitter systems in cortical and subcortical regions. Beyond the negative impact on disability and quality of life, the presence and severity of cognitive symptoms may limit adjustments of dopamine replacement therapy along disease course. This review focuses on the consequences of the administration of monoamine-oxidase type B-inhibitors (MAOB-I) on cognition in PD patients. Two drugs (selegiline and rasagiline) are available for treatment of motor symptoms of PD as monotherapy or in combination with L-DOPA or dopamine agonists in stable and fluctuating patients, a further drug (safinamide) is usable in fluctuating subjects solely. The results of available studies indicate differential effects according to disease stage and drug features. In early, non-fluctuating patients, selegiline and rasagiline ameliorated prefrontal executive functions, similarly to other dopaminergic drugs. Benefit on some executive functions was maintained in more advanced, fluctuating, patients, despite the tendency of worsening of prefrontal inhibitory control activity. Interestingly, high-dose safinamide improved inhibitory control in fluctuating patients. The benefit of high-dose safinamide on prefrontal inhibitory control mechanisms may stem from its dual mechanism of action, allowing reduction of excessive glutamatergic transmission, in turn secondary to increased cortical dopaminergic input
Type-B monoamine oxidase inhibitors in neurological diseases: clinical applications based on preclinical findings
Type-B monoamine oxidase inhibitors, encompassing selegiline, rasagiline, and safinamide, are available to treat Parkinson's disease. These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease. There is also evidence supporting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease, such as mood deflection, cognitive impairment, sleep disturbances, and fatigue. Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors, particularly glial cell line-derived neurotrophic factor, which support dopaminergic neurons. Besides, safinamide may interfere with neurodegenerative mechanisms, counteracting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity. Due to the dual mechanism of action, the new generation of type-B monoamine oxidase inhibitors, including safinamide, is gaining interest in other neurological pathologies, and many supporting preclinical studies are now available. The potential fields of application concern epilepsy, Duchenne muscular dystrophy, multiple sclerosis, and above all, ischemic brain injury. The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline, rasagiline, and safinamide in Parkinson's disease and beyond, focusing on possible future therapeutic applications
The Story behind the Mask: A Narrative Review on Hypomimia in Parkinson’s Disease
Facial movements are crucial for social and emotional interaction and well-being. Reduced facial expressions (i.e., hypomimia) is a common feature in patients with Parkinson’s disease (PD) and previous studies linked this manifestation to both motor symptoms of the disease and altered emotion recognition and processing. Nevertheless, research on facial motor impairment in PD has been rather scarce and only a limited number of clinical evaluation tools are available, often suffering from poor validation processes and high inter- and intra-rater variability. In recent years, the availability of technology-enhanced quantification methods of facial movements, such as automated video analysis and machine learning application, led to increasing interest in studying hypomimia in PD. In this narrative review, we summarize the current knowledge on pathophysiological hypotheses at the basis of hypomimia in PD, with particular focus on the association between reduced facial expressions and emotional processing and analyze the current evaluation tools and management strategies for this symptom, as well as future research perspectives
Age at Onset Influences Progression of Motor and Non-Motor Symptoms during the Early Stage of Parkinson’s Disease: A Monocentric Retrospective Study
The interactions between the age at onset with other pathogenic mechanisms and the interplays between the disease progression and the aging processes in Parkinson’s disease (PD) remain undefined, particularly during the first years of illness. Here, we retrospectively investigated the clinical presentation and evolution of the motor and non-motor symptoms and treatment-related complications during the first 5 years of illness in subjects categorized according to age at onset. A total of 131 subjects were divided into “Early-Onset-PD” (EOPD; onset ≤49 years), “Middle-Onset-PD” (MOPD; onset 50–69 years) and “Late-Onset-PD” (LOPD; onset ≥70 years). The T0 visit was set at the time of the clinical diagnosis; the T1 visit was 5 years (±5 months) later. At T0, there were no significant differences in the motor features among the groups. At T1, the LOPD patients displayed a significantly higher frequency of gait disturbances and a higher frequency of postural instability. Moreover, at T1, the LOPD subjects reported a significantly higher frequency of non-motor symptoms; in particular, cardiovascular, cognitive and neuropsychiatric domains. The presented results showed a significantly different progression of motor and non-motor symptoms in the early course of PD according to the age at onset. These findings contribute to the definition of the role of age at onset on disease progression and may be useful for the pharmacological and non-pharmacological management of PD
Effects of levodopa/carbidopa intestinal gel infusion on autonomic symptoms in advanced Parkinson’s disease: a systematic review
Purpose Autonomic failure has a major impact on the quality of life of individuals with Parkinson’s disease (PD), especially in advanced stages of the disease. Levodopa/carbidopa intestinal gel (LCIG) infusion is a well-established treatment for advanced PD with severe motor fluctuations and provides substantial benefit in managing some non-motor symptoms (NMS), such as sleep, fatigue, and neuropsychiatric issues. The effect of LCIG on autonomic symptoms is by contrast not well known. Here we performed a systematic review on the influence of LCIG therapy on autonomic dysfunction in PD individuals. Methods Following the PRISMA guidelines, we systematically searched for studies that included autonomic outcome measures in LCIG-treated PD individuals, limiting the search to articles written in English and published between January 2005 and June 2023. We evaluated improvement, stability, or worsening of gastrointestinal, urinary, and cardiovascular symptoms at six different timepoints according to clinimetric scale changes compared to baseline. Data on autonomic adverse events (AEs) possibly related to LCIG treatment were also collected. Results Of the 1476 studies identified in the initial search, 16 ultimately met the inclusion criteria and underwent quality assessment and data extraction, with data from 1361 PD patients (18.3 months mean follow-up). Thirteen studies reported improvement or stability of gastrointestinal, urinary, and cardiovascular symptoms over the interventional period. One study found a worsening of cardiovascular symptoms and two of urological symptoms. Regarding safety, seven studies reported gastrointestinal (8.4%), urinary (0.5%), and cardiovascular (1.1%) autonomic LCIG-related AEs. Conclusions LCIG infusion may help to reduce the burden of autonomic symptoms in advanced PD. Prospective studies specifically addressing the effect of LCIG on autonomic function in advanced PD are warranted
Feasibility, Safety, and Effectiveness of Telerehabilitation in Mild-to-Moderate Parkinson's Disease
INTRODUCTION: Parkinson's disease (PD) patients frequently engage in rehabilitation to ameliorate symptoms. During the Coronavirus disease 2019 (COVID-19) pandemic, access to rehabilitation programs has been markedly limited, consequently, telerehabilitation gained popularity. In this prospective, open-label, and pilot study, we aimed to investigate feasibility, safety, and efficacy of telerehabilitation in mild-to-moderate PD patients. MATERIALS AND METHODS: Twenty-three PD patients, with Hoehn and Yahr stage 30-min of self-conducted exercises per week. Patients received video tutorials of exercises and were asked to keep a diary of sessions. At baseline (T0), at the end of the intervention (T1), and 1 month after the end of treatment (T2), patients were remotely assessed with MDS-UPDRS part I-III, PDQ-39, Functional Independence Measure (FIM), and Frontal Assessment Battery scales, respectively. Acceptable compliance to the program was defined as >60% matching of frequency and duration of sessions, whereas optimal compliance was set at >80% matching. RESULTS: The dropout rate was 0%. Over 85% of patients reached acceptable adherence cut-off and around 70% reached optimal one. No adverse events were reported during sessions. The repeated measure analysis of variance (rANOVA) showed a significant effect of factor “time” for MDS-UPDRS-III (p < 0.0001) with a mean reduction of 4.217 points between T0 and T1 and return to baseline at T2. No significant effect was found for other outcome measures. CONCLUSION: Our findings demonstrate that telerehabilitation is safe, feasible, and effective on motor symptoms in mild-to-moderate PD patients
