European Academy of Neurology/Movement Disorder Society - European Section guideline on the treatment of Parkinson's disease: I. Invasive therapies

BACKGROUND AND PURPOSE: This update of the treatment guidelines was commissioned by the European Academy of Neurology and the European section of the Movement Disorder Society. Although these treatments are initiated usually in specialized centers, the general neurologist and general practitioners taking care of PD patients should know the therapies and their place in the treatment pathway. METHODS: Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to assess the spectrum of approved interventions including deep brain stimulation (DBS) or brain lesioning with different techniques (radiofrequency thermocoagulation, radiosurgery, magnetic resonance imaging-guided focused ultrasound surgery [MRgFUS] of the following targets: subthalamic nucleus [STN], ventrolateral thalamus, and pallidum internum [GPi]). Continuous delivery of medication subcutaneously (apomorphine pump) or through percutaneous ileostomy (intrajejunal levodopa/carbidopa pump [LCIG]) was also included. Changes in motor features, health-related quality of life (QoL), adverse effects, and further outcome parameters were evaluated. Recommendations were based on high-class evidence and graded in three gradations. If only lower class evidence was available but the topic was felt to be of high importance, clinical consensus of the guideline task force was gathered. RESULTS: Two research questions have been answered with eight recommendations and five clinical consensus statements. Invasive therapies are reserved for specific patient groups and clinical situations mostly in the advanced stage of Parkinson's disease (PD). Interventions may be considered only for special patient profiles, which are mentioned in the text. Therapy effects are reported as change compared with current medical treatment. STN-DBS is the best-studied intervention for advanced PD with fluctuations not satisfactorily controlled with oral medications; it improves motor symptoms and QoL, and treatment should be offered to eligible patients. GPi-DBS can also be offered. For early PD with early fluctuations, STN-DBS is likely to improve motor symptoms, and QoL and can be offered. DBS should not be offered to people with early PD without fluctuations. LCIG and an apomorphine pump can be considered for advanced PD with fluctuations not sufficiently managed with oral treatments. Unilateral MRgFUS of the STN can be considered for distinctly unilateral PD within registries. Clinical consensus was reached for the following statements: Radiosurgery with gamma radiation cannot be recommended, unilateral radiofrequency thermocoagulation of the pallidum for advanced PD with treatment-resistant fluctuations and unilateral radiofrequency thermocoagulation of the thalamus for resistant tremor can be recommended if other options are not available, unilateral MRgFUS of the thalamus for medication-resistant tremor of PD can be considered only within registries, and unilateral MRgFUS of the pallidum is not recommended. CONCLUSIONS: Evidence for invasive therapies in PD is heterogeneous. Only some of these therapies have a strong scientific basis. They differ in their profile of effects and have been tested only for specific patient groups

Konstantin N. Tretiakoff in Brazil a historical perspective and discussion of his contribution to brazilian neuroscience Konstantin N. Tretiakoff no Brasil: uma perspectiva histórica e discussão de sua contribuição à neurociência brasileira

The Hospício de Juquery, near the city of São Paulo (Brazil) was founded in 1896 and after few years it was decided that the institution should have the best possible facilities to study neuropathology. In 1921, a young psychiatrist, Antonio Carlos Pacheco e Silva was sent to the Hôpital de la Salpêtrière (Paris) to study neuropathology. There, Pacheco e Silva (later Prof.Pacheco e Silva) befriended Konstantin N. Tretiakoff accepted an invitation to become the first Chairman of the newly created neuropathology department of the Hospício de Juquery. During his stay in this institution, from 1922 to 1924 or early 1925, he worked very hardly and produced many publications. Here we present and comment some of the papers he published in a Journal (Memórias do Hospício de Juquery - "Memoirs de l'Hôspice de Juquery"), which had been recently created and present some information of this poorly known period of his life.<br>O Hospício de Juquery, perto da cidade de São Paulo (Brasil) foi fundado em 1896 e depois de poucos anos o Prof. Franco da Rocha, seu fundador, e os demais responsáveis pela instituição, com a ajuda do Governo do Estado de São Paulo, decidiram que deveriam criar as melhores instalações para o estudo da neuropatologia. Em 1921, o jovem psiquiatra Antonio Carlos Pacheco e Silva foi enviado para o Hôpital de la Salpêtrière (Paris) para estudar neuropatologia. Nessa instituição, Prof. Pacheco e Silva tornou-se amigo de um jovem neuropatologista, neurologista e psiquiatra russo Konstantin N. Tretiakoff que aceitou o desafio de chefiar o recém criado Departamento de Neuropatologia do Hospício de Juquery. Durante sua estada entre nós, de 1922 a 1924 ou início de 1925, ele trabalhou muito aplicadamente e produziu muitas publicações. Aqui nós apresentamos e comentamos alguns destes trabalhos que ele e seus associados publicaram em um novo Jornal (Memórias do Hospício de Juquery - "Memoirs de l'Hospice de Juquery") que circulou entre 1924 e 1927. Ademais, apresentamos algumas informações sobre esta parte menos conhecida de sua biografia

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson’s Disease at the Prodromal Stage

Parkinson’s disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD

Searching for Biomarkers in the Blood of Patients at Risk of Developing Parkinson&rsquo;s Disease at the Prodromal Stage

Parkinson&rsquo;s disease (PD) is diagnosed many years after its onset, under a significant degradation of the nigrostriatal dopaminergic system, responsible for the regulation of motor function. This explains the low effectiveness of the treatment of patients. Therefore, one of the highest priorities in neurology is the development of the early (preclinical) diagnosis of PD. The aim of this study was to search for changes in the blood of patients at risk of developing PD, which are considered potential diagnostic biomarkers. Out of 1835 patients, 26 patients were included in the risk group and 20 patients in the control group. The primary criteria for inclusion in a risk group were the impairment of sleep behavior disorder and sense of smell, and the secondary criteria were neurological and mental disorders. In patients at risk and in controls, the composition of plasma and the expression of genes of interest in lymphocytes were assessed by 27 indicators. The main changes that we found in plasma include a decrease in the concentrations of l-3,4-dihydroxyphenylalanine (L-DOPA) and urates, as well as the expressions of some types of microRNA, and an increase in the total oxidative status. In turn, in the lymphocytes of patients at risk, an increase in the expression of the DA D3 receptor gene and the lymphocyte activation gene 3 (LAG3), as well as a decrease in the expression of the Protein deglycase DJ-1 gene (PARK7), were observed. The blood changes we found in patients at risk are considered candidates for diagnostic biomarkers at the prodromal stage of PD

Confusion of evidence‐based reviews and guidelines

© 2023 European Academy of NeurologyHariz and colleagues [1] argue that the new EAN/MDS GL contradicts the repeated endorsements of pallidotomy by the MDS. The MDS has previously published “evidence based medicine (EBM) reviews,” which appraise each treatment on the basis of welldefined criteria but are not GLs. Clinical GLs, such as the new EAN/MDS GL, also take into consideration other variables, including context, summarizing the current medical knowledge, weighing the benefits and harms of treatments, and giving specific recommendations based on this information. The specific GRADE GL methodology allows for the evaluation of available scientific evidence with a sophisticated evaluation process that includes grading the strength of the evidence and the certainty of that evidence, out of which the recommendations are developed. These steps are well documented in our appendices 1 and 2 for methodology and appendices 3 and 4 for outcomes. Thus, the case of radiofrequency pallidotomy and deep brain stimulation (DBS) of the pallidum, which is discussed by Hariz et al, illustrates the difference between EBM reviews and GLs. The EBM review ranks pallidotomy at the same level as globus pallidus internus (GPi)-DBS: both treatments are considered “efficacious,” “clinically useful,” and coming with a “clinically acceptable risk with specialized monitoring,” but it does not express whether the treatments are equal in their application in patients overall. In our GL using the GRADE methodology, in contrast, GPi-DBS is recommended, whereas pallidotomy is recommended only with restrictions.info:eu-repo/semantics/publishedVersio