Parkinson\'s disease (PD) is a progressive and disabling neurodegenerative disease that rapidly worsens and results in premature mortality if left untreated. Although levodopa is the gold standard treatment for PD globally, its accessibility and affordability are severely limited in low- and middle-income countries worldwide. In this scenario, Mucuna pruriens (MP), a leguminous plant growing wild in tropical regions, emerges as a potential alternative or adjunct to levodopa-based medications due to its cost-effectiveness and global natural availability. Recent studies have demonstrated that MP can significantly ameliorate motor symptoms, although tolerability may vary. The proposition that MP could play a pivotal role in providing affordable and symptomatic relief for PD in low- and middle-income countries is grounded in its promising therapeutic profile, yet caution is warranted until more comprehensive data on the long-term safety and efficacy of MP become available. This manuscript summarizes the knowledge gained about MP by the authors, focusing on how to cultivate, store, and provide it to patients in the safest and most effective way in clinical trials. We aim to increase clinical trials investigating its safety and efficacy in PD, before promoting individual use of MP on a global scale, particularly in countries where availability and affordability of levodopa-based medications is still limited.

BACKGROUND: The decision to choose invasive treatments for Parkinson\'s disease (PD) is complex and needs careful consideration.
OBJECTIVE: Although the recommendations of the European Academy of Neurology/Movement Disorder Society European Section guideline for invasive therapies of PD are useful, the different clinical profiles of people with PD who seek advice for possible invasive therapy need further attention.
RESULTS: Here we describe 8 clinical standard situations of people with PD unsatisfied with their current oral treatment where invasive therapies may be considered. These are PD patients presenting with the following symptoms: (1) severe motor fluctuations, (2) beginning of levodopa-responsive fluctuations, severe tremor at (3) young or (4) advanced age, (5) impulse control disorders and related behavioral disorders, (6) hallucinations and psychosis, (7) minimal cognitive impairment or mild dementia, and (8) patients in need of palliative care. For some of these conditions, evidence at lower level or simple clinical considerations exist.
CONCLUSIONS: There are no one-fits-all answers, but physician and patient should discuss each option carefully considering symptom profile, psychosocial context, availability of therapy alternatives, and many other factors. The current paper outlines our proposed approach to these circumstances.

Opicapone (OPC) is a third-generation peripheral catechol-O-methyl transferase inhibitor (COMT-i) approved as add-on therapy to levodopa/DOPA decarboxylase inhibitors (DDCI) combinations in Parkinson\'s disease (PD) patients with end-of-dose motor fluctuations. While the OPC effectiveness on motor symptoms is well known, there is still uncertainty about the timing of introduction, the management of levodopa dose, and the efficacy on non-motor symptoms (NMS).
A group of PD experts participated in a consensus activity composed of the Nominal Group Technique (NGT) and the Delphi method to better define the role of OPC. A list of statements was defined with the NGT and voted on through an online Delphi process by a panel of 85 Italian clinicians.
24 statements were selected for the Delphi voting. Most statements (n=15, 62%) reached a consensus. A wide agreement was reached about the efficacy of OPC in treating motor fluctuations, including early morning akinesia and nocturnal akinesia. The panel widely agreed about the effectiveness of OPC in early fluctuating patients. The long-lasting inhibitory effect of OPC was recognized as an advantage over other COMT-i, resulting in a single daily dose and greater ease of introduction into the levodopa therapeutic regimen.
The efficacy of OPC observed in the clinical trials for the management of PD patients with motor fluctuations is also experienced in clinical practice. The review of the current positioning of OPC from the late to early stages of the disease may represent an important step in the evolution of the PD therapeutic approach.

Parkinson\'s disease (PD) is in some cases predisposed-or-caused by genetic variants, contributing to the expression of different phenotypes. Regardless of etiology, as the disease progresses, motor fluctuations and/or levodopa-induced dyskinesias limit the benefit of pharmacotherapy. Device-aided therapies are good alternatives in advanced disease, including deep brain stimulation (DBS), levodopa-carbidopa intestinal gel, and continuous subcutaneous infusion of apomorphine. Candidate selection and timing are critical for the success of such therapies. Genetic screening in DBS cohorts has shown a higher proportion of mutation carriers than in general cohorts, suggesting that genetic factors may influence candidacy for advanced therapies. The response of monogenic PD to device therapies is not well established, and the contribution of genetic information to decision-making is still a matter of debate. The limited evidence regarding gene-dependent response to device-aided therapies is reviewed here. An accurate understanding of the adequacy and responses of different mutation carriers to device-aided therapies requires the development of specific studies with long-term monitoring.

To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians.
A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an Institute of Medicine-compliant process to ensure transparency and patient engagement. Recommendations were supported by structured rationales, integrating evidence from the systematic review, related evidence, principles of care, and inferences from evidence.
Initial treatment with levodopa provides superior motor benefit compared to treatment with dopamine agonists, whereas levodopa is more likely than dopamine agonists to cause dyskinesia. The comparison of different formulations of dopamine agonists yielded little evidence that any one formulation or method of administration is superior. Long-acting forms of levodopa and levodopa with entacapone do not appear to differ in efficacy from immediate-release levodopa for motor symptoms in early disease. There is a higher risk of impulse control disorders associated with the use of dopamine agonists than levodopa. Recommendations on initial therapy for motor symptoms are provided to assist the clinician and patient in choosing between treatment options and to guide counseling, prescribing, and monitoring of efficacy and safety.

BACKGROUND: Motor fluctuations are one of the most common complications of Parkinson\'s disease and their treatment is still a complex matter. Therefore, from the Neurology Movement Disorders Group we present our clinical experience in the treatment of these complications, with the intention of it being useful in decision-making in daily clinical practice.
METHODS: Nineteen questions were developed based on a literature review and an open survey answered by members of this group. These issues were discussed in two phases, using the Delphi methodology. Considering the results of the survey, levodopa dose adjustment and dopamine agonists are the option with the best efficacy/tolerability ratio in the treatment of motor fluctuations. Rotigotine is useful in the motor fluctuations associated with gastroparesis, and intermittent subcutaneous apomorphine has positive effects in patients with unpredictable off periods. The most relevant adverse effect associated with dopamine agonists is impulse control disorder. Catechol-O-methyltransferase inhibitors are useful in the initial stages of motor fluctuations, especially in wearing off. Monoamine oxidase inhibitors are generally drugs that are well-tolerated and useful in motor fluctuations. If these measures are not effective, second-line treatments should be indicated on a case-by-case basis.
CONCLUSIONS: The clinical profile of patients with Parkinson\'s disease is paramount in deciding the most appropriate therapy for the treatment of motor fluctuations.
BACKGROUND: Experiencia clínica en el tratamiento de las fluctuaciones motoras en la enfermedad de Parkinson. Consenso Delphi de un grupo de expertos en trastornos del movimiento.
Introducción. Las fluctuaciones motoras son una de las complicaciones más frecuentes en la enfermedad de Parkinson y su tratamiento sigue siendo complejo. Por ello, desde el Grupo de Trastornos del Movimiento de la Asociación Madrileña de Neurología presentamos nuestra experiencia clínica en el tratamiento de estas complicaciones, con la intención de que sea de utilidad en la toma de decisiones en la práctica clínica diaria. Desarrollo. Se elaboraron 19 preguntas a partir de una revisión bibliográfica y una encuesta abierta respondida por los miembros de dicho grupo. Dichas cuestiones se debatieron en dos fases, utilizando la metodología Delphi. Considerando los resultados de la encuesta, el ajuste de la dosis de levodopa y los agonistas dopaminérgicos son la opción con mejor relación eficacia/tolerabilidad en el tratamiento de las fluctuaciones motoras. La rotigotina es útil en las fluctuaciones motoras asociadas a gastroparesia, y la apomorfina subcutánea intermitente, en pacientes con off impredecible. El efecto adverso más relevante asociado a los agonistas dopaminérgicos es el trastorno del control de impulsos. Los inhibidores de la catecol-O-metiltransferasa son útiles en las fluctuaciones motoras de inicio, especialmente en el wearing off. Los inhibidores de la monoaminooxidasa son fármacos, en general, bien tolerados y útiles en las fluctuaciones motoras. En caso de que estas medidas no resulten eficaces, se deben indicar terapias de segunda línea de manera individualizada. Conclusión. El perfil clínico del paciente con enfermedad de Parkinson es primordial para decidir la terapia más adecuada en el tratamiento de las fluctuaciones motoras.

Adherence to the 2011 Japanese guidelines for treatment of Parkinson\'s disease (PD) in real-life practice is unknown.
In this retrospective longitudinal observational study, we examined patterns and trends in anti-PD drug prescriptions in 20,936 patients (≥30 years of age with newly diagnosed PD [International Classification of Diseases-Tenth code G20 or PD Hoehn and Yahr scale 1-5] and one or more prescriptions) using nationwide registry data between 2008 and 2016. Data are presented as descriptive statistics.
Half (49.6%) of the patients received levodopa (L-dopa) monotherapy, followed by non-ergot dopamine agonists (DA) prescribed as monotherapy (8.3%) or with L-dopa (8.1%). Consistent with the guidelines, 75% of patients were prescribed within 13 days of initial diagnosis; L-dopa monotherapy was the most prescribed drug in patients ≥70 years of age, whereas non-ergot DA monotherapy was more likely to be prescribed than L-dopa in patients between 30 and 50 years of age. Inconsistent with the guidelines, L-dopa monotherapy was the most prescribed drug in patients between 51 and 69 years of age. Over the course of 4 years of treatment, the prescription rate of L-dopa monotherapy and non-ergot DA monotherapy decreased by 63.7% and 44.1%, respectively, whereas that of L-dopa and non-ergot DA combination therapy increased by 103.7%. Combination therapy with L-dopa, non-ergot DA, and monoamine oxidase-B inhibitors was gradually increased at a later stage.
These results highlight that the state of PD treatment in Japan adheres to most of the recommendations in the 2011 national guidelines, but also precedes the 2018 guidelines.

Percutaneous endoscopic gastrostomy with jejunal extension (PEG/J) was first described in 1998 and has become the standard technique for fixing the tube in place for levodopa carbidopa intestinal gel (LCIG) infusion. The Romanian Society of Digestive Endoscopy (RSDE) decided to create a consensus paper to meet the needs in medical training and practice. After reviewing the available published data and existing recommendations, a consensus process was carried out involving the leaders of opinion in this field. The resulting text and recommendations were approved, after reaching expert consensus, and reflects the views of the RSDE for the best practice of PEG/J tube placement. The pull through method (\"pull technique\") is the prevailing PEG-tube placement procedure in Romania. The procedure can be performed with intravenous sedation combined with local anesthesia. Although minor complications are common, serious complications are infrequent, and the tube insertion procedures have a good safety record. Redo procedures are sometimes necessary and clinicians should be aware of these situations.

Over the last few decades, several delayed-start trials have suggested that early introduction of dopamine replacement therapy can improve the prognosis of Parkinson\'s disease (PD). Moreover, several observations support that L-dopa is non toxic to normal and diseased substantia nigra in humans. Thus, the clinical practice guideline 2018 for PD recommends L-dopa as an initial treatment for PD, in principle. More recently, several potential disease-modifying therapies have been reported to be effective. Furthermore, several recent studies suggest that exercise can be beneficial in delaying disease progression.

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