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1.
Georgian Med News ; (306): 117-122, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33130658

RESUMO

60 patients of the Narcological Clinic "Neogene" were enrolled into the study. The following participation criteria were used: a diagnosis of mental and behavioral disorders associated with ephedrone use; withdrawal state. Toxic encephalopathy; age - 20-65 years; gender - male. Patients were selected and diagnosed for the study according to ICD-10 criteria. The study was conducted in compliance with bioethical principles, based on informed consent. The main study group (Group I) consisted of 45 patients and the control group (Group II) - of 15 patients. The study strictly observed anonymity and confidentiality of the participants. Thiogamma drug (alpha-lipoic acid, meglumine salt, manufacturer WÖRWAG PHARMA) with a daily dose of 600 mg was added for a duration of one month, to the standard treatment regimen of the patients of the Group I in both inpatient and outpatient settings. The patients (both inpatient and outpatient) in the Group II were treated with placebo drug along with standard treatment for the same period. Clinico-neurological disorders of the patients were evaluated before and after a one-month therapy course. Neurological examination and Unified Parkinson Disease Rating Scale - UPDSR - were used. Based on the study materials it can be reported that the users of homemade ephedron group psychostimulants ("Jeff") had neurological disorders, mainly manifested with the symptoms of Parkinson's disease; with well-expressed dystonia, postural instability, pseudobulbar and vegetative syndromes. As a result of the treatment, a decrease in the scores on the UPDSR was observed (improved condition) in patients of both groups, however, the improvement was greater expressed in the patients of Group I where Thiogamma (alpha-lipoic acid meglumine salt) drug was added to the standard treatment protocol. The above results clearly speak to the effectiveness of "Thiogamma" in the treatment of neurological disorders caused by the use of homemade psychostimulants ("Jeff").


Assuntos
Transtornos Mentais , Doença de Parkinson , Propiofenonas , Protocolos Clínicos , Humanos , Masculino , Doença de Parkinson/tratamento farmacológico
2.
Zh Nevrol Psikhiatr Im S S Korsakova ; 120(10. Vyp. 2): 80-88, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33205935

RESUMO

Disturbances in sleep and wakefulness are important symptoms of Parkinson's disease (PD) and are associated with negative effects on patients' quality of life. The analysis of literature on the relationship between RLS and PD revealed three main hypotheses explaining the relatively high incidence of RLS in PD: (1) RLS can be considered as an early (prodromal) manifestation or a predictor of PD that can outpace its main symptoms by several years (by analogy with conduct disorder during sleep with REM); (2) the high incidence of RLS in the advanced stage of PD may be associated with augmentation of previously latent RLS symptoms during prolonged dopaminergic therapy of PD; (3) a significant proportion of RLS cases in PD patients are not «classical¼ RLS, but represent, for example, manifestations of motor or non-motor fluctuations or a special form of stereotypy in the legs. Further research is needed to determine if any of these statements are true.


Assuntos
Doença de Parkinson , Síndrome das Pernas Inquietas , Humanos , Perna (Membro) , Doença de Parkinson/complicações , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/epidemiologia , Qualidade de Vida , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/etiologia , Sono
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5406-5409, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019203

RESUMO

More than one million people currently live with Parkinson's Disease (PD) in the U.S. alone. Medications, such as levodopa, can help manage PD symptoms. However, medication treatment planning is generally based on patient history and limited interaction between physicians and patients during office visits. This limits the extent of benefit that may be derived from the treatment as disease/patient characteristics are generally non-stationary. Wearable sensors that provide continuous monitoring of various symptoms, such as bradykinesia and dyskinesia, can enhance symptom management. However, using such data to overhaul the current static medication treatment planning approach and prescribe personalized medication timing and dosage that accounts for patient/care-giver/physician feedback/preferences remains an open question. We develop a model to prescribe timing and dosage of medications, given the motor fluctuation data collected using wearable sensors in real-time. We solve the resulting model using deep reinforcement learning (DRL). The prescribed policy determines the optimal treatment plan that minimizes patient's symptoms. Our results show that the model-prescribed policy outperforms the static a priori treatment plan in improving patients' symptoms, providing a proof-of-concept that DRL can augment medical decision making for treatment planning of chronic disease patients.


Assuntos
Discinesias , Doença de Parkinson , Tomada de Decisão Clínica , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 6001-6004, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33019339

RESUMO

Dyskinesias are abnormal involuntary movements that patients with mid-stage and advanced Parkinson's disease (PD) may suffer from. These troublesome motor impairments are reduced by adjusting the dose or frequency of medication levodopa. However, to make a successful adjustment, the treating physician needs information about the severity rating of dyskinesia as patients experience in their natural living environment. In this work, we used movement data collected from the upper and lower extremities of PD patients along with a deep model based on Long Short-Term Memory to estimate the severity of dyskinesia. We trained and validated our model on a dataset of 14 PD subjects with dyskinesia. The subjects performed a variety of daily living activities while their dyskinesia severity was rated by a neurologist. The estimated dyskinesia severity ratings from our developed model highly correlated with the neurologist-rated dyskinesia scores (r=0.86 (p<0.001) and 1.77 MAE (6%)) indicating the potential of the developed the approach in providing the information required for effective medication adjustments for dyskinesia management.


Assuntos
Discinesias , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Antiparkinsonianos/efeitos adversos , Discinesias/diagnóstico , Humanos , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3666-3669, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018796

RESUMO

This study has investigated the efficiency of voice features in estimating the motor Unified Parkinson's Disease Rating Scale (UPDRS) score in Parkinson's disease (PD) patients. A total of 26 PD patients (mean age = 72) and 22 control subjects (mean age = 66.91) were recruited for the study. The sustained phonation /a/, /u/ and /m/ were collected in both off-state and on-state of Levodopa medication. The average motor UPDRS for PD off-state patients was 27.31, on-state was 20.42 and that of controls was 2.63. Voice features were extracted from the phonation tasks and were reduced to the most relevant 6 features for each phonation task using the Least Absolute Shrinkage and Selection Operator (LASSO) feature ranking method. The correlation between the reduced features and motor UPDRS was tested using the Spearman correlation coefficient test. AdaBoost regression learner was trained and used for automatically estimating the motor UPDRS score using the voice features. The results show that the vocal features for /m/ performed best by estimating the motor UPDRS score for PD off-state with the mean absolute error (MAE) of 3.52 and 5.90 for PD on-state. This study shows that assessment of voice can be used for day to day remote monitoring of PD patients.


Assuntos
Doença de Parkinson , Voz , Humanos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Fonação
6.
Int J Nanomedicine ; 15: 7615-7626, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116491

RESUMO

Purpose: Although single-walled nanotubes (SWNTs) with functional groups have been suggested as a potential nanomedicine to treat neuronal disorders, effective routes to administer SWNTs have not been compared thus far. The blood-brain barrier is a considerable challenge for the development of brain-targeting drugs, and therefore functionalized SWNT routes of administration have been needed for testing Parkinson's disease (PD) treatment. Here, effective administration routes of functionalized SWNTs were evaluated in PD mouse model. Methods: Three different administration routes were tested in PD mouse model. Functionalized SWNTs were injected directly into the lateral ventricle three days before (Method 1) or after (Method 2) 6-hydroxydopamine (6-OHDA) injection to compare the protective effects of SWNTs against dopaminergic neuronal death or functionalized SWNTs were injected intravenously at three and four days after 6-OHDA injection (Method 3). Asymmetric behaviors and histological assessment from all animals were performed at two weeks after 6-OHDA injection. Results: Ventricular injections of SWNTs both before or after 6-OHDA exposure protected dopaminergic neurons both in the substantia nigra and striatum and alleviated rotational asymmetry behavior in PD mice. Moreover, intravenous administration of SWNTs three and four days after 6-OHDA injection also prevented neuronal death and PD mice behavioral impairment without apparent cytotoxicity after six months post-treatment. Conclusion: Our study demonstrates that functionalized SWNTs could effectively protect dopaminergic neurons through all administration routes examined herein. Therefore, SWNTs are promising nanomedicine agents by themselves or as therapeutic carriers to treat neuronal disorders such as PD.


Assuntos
Neurônios Dopaminérgicos/patologia , Nanotubos de Carbono/química , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/farmacologia , Oxidopamina/toxicidade , Administração Intravenosa , Animais , Antioxidantes/farmacologia , Comportamento Animal , Morte Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos ICR , Nanotubos de Carbono/ultraestrutura , Crescimento Neuronal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Polietilenoglicóis/química , Tirosina 3-Mono-Oxigenase/metabolismo
7.
Medicine (Baltimore) ; 99(35): e21576, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871874

RESUMO

BACKGROUND: Cellular energetics play an important role in Parkinsons disease etiology, but no treatments directly address this deficiency. Our past research showed that treatment with febuxostat and inosine increased blood hypoxanthine and ATP in healthy adults, and a preliminary trial in 3 Parkinson's disease patients suggested some symptomatic improvements with no adverse effects. METHODS: To examine the efficacy on symptoms and safety in a larger group of Parkinsons disease patients, we conducted a single-arm, open-label trial at 5 Japanese neurology clinics and enrolled thirty patients (nmales = 11; nfemales = 19); 26 patients completed the study (nmales = 10; nfemales = 16). Each patient was administered febuxostat 20 mg and inosine 500 mg twice-per-day (after breakfast and dinner) for 8 weeks. The primary endpoint was the difference of MDS-UPDRS Part III score immediately before and after 57 days of treatment. RESULTS: Serum hypoxanthine concentrations were raised significantly after treatment (Pre = 11.4 µM; Post = 38.1 µM; P < .0001). MDS-UPDRS Part III score was significantly lower after treatment (Pre = 28.1 ±â€Š9.3; Post = 24.7 ±â€Š10.8; mean ±â€ŠSD; P = .0146). Sixteen adverse events occurred in 13/29 (44.8%) patients, including 1 serious adverse event (fracture of the second lumbar vertebra) that was considered not related to the treatment. CONCLUSIONS: The results of this study suggest that co-administration of febuxostat and inosine is relatively safe and effective for improving symptoms of Parkinsons disease patients. Further controlled trials need to be performed to confirm the symptomatic improvement and to examine the disease-modifying effect in long-term trials.


Assuntos
Febuxostat/uso terapêutico , Supressores da Gota/uso terapêutico , Inosina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Trifosfato de Adenosina/sangue , Administração Oral , Idoso , Estudos de Casos e Controles , Quimioterapia Combinada , Febuxostat/administração & dosagem , Febuxostat/efeitos adversos , Feminino , Supressores da Gota/administração & dosagem , Supressores da Gota/efeitos adversos , Humanos , Hipoxantina/sangue , Inosina/administração & dosagem , Inosina/efeitos adversos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/fisiopatologia , Segurança , Resultado do Tratamento , Xantina Desidrogenase/antagonistas & inibidores
8.
Nat Commun ; 11(1): 4885, 2020 09 28.
Artigo em Inglês | MEDLINE | ID: mdl-32985503

RESUMO

Parkinson's disease (PD) affects millions of patients worldwide and is characterized by alpha-synuclein aggregation in dopamine neurons. Molecular tweezers have shown high potential as anti-aggregation agents targeting positively charged residues of proteins undergoing amyloidogenic processes. Here we report that the molecular tweezer CLR01 decreased aggregation and toxicity in induced pluripotent stem cell-derived dopaminergic cultures treated with PD brain protein extracts. In microfluidic devices CLR01 reduced alpha-synuclein aggregation in cell somas when axonal terminals were exposed to alpha-synuclein oligomers. We then tested CLR01 in vivo in a humanized alpha-synuclein overexpressing mouse model; mice treated at 12 months of age when motor defects are mild exhibited an improvement in motor defects and a decreased oligomeric alpha-synuclein burden. Finally, CLR01 reduced alpha-synuclein-associated pathology in mice injected with alpha-synuclein aggregates into the striatum or substantia nigra. Taken together, these results highlight CLR01 as a disease-modifying therapy for PD and support further clinical investigation.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Neurônios Dopaminérgicos/efeitos dos fármacos , Organofosfatos/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Substâncias Protetoras/administração & dosagem , Animais , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Humanos , Masculino , Camundongos , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Agregados Proteicos/efeitos dos fármacos , alfa-Sinucleína/química , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
10.
Mov Disord ; 35(10): 1712-1716, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32776601

RESUMO

BACKGROUND: The aim of this study was to know the impact of the coronavirus disease 2019 (COVID-19) pandemic on Spanish patients with Parkinson's disease (PD). METHODS: This is a descriptive, observational, cross-sectional study. An anonymous online survey with 95 questions was distributed among patients. Responses were collected from 11 May 2020 to 20 July 2020. RESULTS: Of a total of 570 questionnaires received, 568 (99.6%) were considered valid for the analysis (mean age, 63.5 ± 12.5 years; 53% females). A total of 553 patients (97.4%) were aware of the COVID-19 pandemic and 68.8% were concerned about it; 95.6% took preventive measures. A total of 484 patients (85.2%) had no contact with cases of COVID-19, and only 15 (2.6%) had confirmed COVID-19. Although up to 72.7% remained active during confinement, 65.7% perceived a worsening of their symptoms. CONCLUSIONS: Spanish patients with PD perceived the COVID-19 pandemic with concern and responsibility. More than half experienced worsening of their symptoms during confinement. © 2020 International Parkinson and Movement Disorder Society.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus , Progressão da Doença , Pandemias , Doença de Parkinson/tratamento farmacológico , Pneumonia Viral , Idoso , Infecções por Coronavirus/complicações , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/complicações , Espanha , Inquéritos e Questionários
11.
PLoS One ; 15(8): e0237472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817705

RESUMO

A higher levodopa dose is a strong risk factor for levodopa-induced dyskinesia (LID) in patients with Parkinson's disease (PD). However, levodopa dose can change during long-term medication. We explored the relationship between levodopa dose and time to onset of LID using longitudinal multicenter data. Medical records of 150 patients who were diagnosed with de novo PD and treated with levodopa until onset of LID were collected. Levodopa dose were assessed as the dose at 6 months from levodopa initiation and rate of dose increase between 6 months and onset of LID. The groups with earlier LID onset had higher levodopa and levodopa-equivalent dose at the first 6 months of treatment and rapid increase in both levodopa and levodopa-equivalent dose. Multivariable linear regression models revealed that female sex, severe motor symptom at levodopa initiation, and higher rate of increase in both levodopa and levodopa-equivalent dose were significantly associated with early onset of LID. The present results demonstrated that rapid increase in levodopa dose or levodopa-equivalent dose is associated with early onset of LID.


Assuntos
Antiparkinsonianos/uso terapêutico , Discinesia Induzida por Medicamentos/diagnóstico , Levodopa/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Idoso , Antiparkinsonianos/efeitos adversos , Relação Dose-Resposta a Droga , Discinesia Induzida por Medicamentos/etiologia , Feminino , Humanos , Levodopa/uso terapêutico , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/patologia , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
12.
PLoS One ; 15(8): e0237498, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32822437

RESUMO

The EARLYSTIM Study compared deep brain stimulation (DBS) with best medical treatment (BMT) over 2-years, showing a between-group difference of 8.0 from baseline in favor of DBS in health-related quality of life (HRQoL), measured with the PDQ-39 SI (summary index). This study obtained complementary information about the importance of the change in HRQoL as measured by the PDQ-39, using anchor-based (Patient Global Impression of Change, PGIC) and distribution-based techniques (magnitude of change, effect size, thresholds, distribution of benefit) applied to the EARLYSTIM study data. Anchor-based techniques showed a difference follow-up-baseline for patients who reported "minimal improvement" of -5.8 [-9.9, -1.6] (mean [95%CI]) in the DBS group vs -2.9 [-9.0, 3.1] in the BMT group. As the vast majority (80.8%) of DBS patients reported "much or very much improvement", this difference was explored for the latter group and amounted to -8.7 for the DBS group and -6.5 in the BMT group. Distribution-based techniques that analyzed the relative change and treatment effect size showed a moderate benefit of the DBS on the HRQoL, whereas a slight worsening was observed in the BMT group. The change in the DBS group (-7.8) was higher than the MIC (Minimally Important Change) estimated value (-5.8 by the anchor; -6.3 by triangulation of thresholds), but not in the BMT (0.2 vs. -3.0 to -5.4, respectively). Almost 90% of the patients in the DBS group declared some improvement (58.3% and 56.7% beyond the estimated MIC), which was significantly different from the BMT group whose proportions were 32.0% and 30.3%, respectively. The number needed to treat to improve ≥1 MIC by DBS vs BMT was 3.8. Change in depression, disability and pain influenced the improvement of the DBS group. DBS improved HRQoL in a high proportion of patients to a significant and moderate degree, at 2 years follow-up.


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson/terapia , Qualidade de Vida , Atividades Cotidianas , Estudos de Coortes , Humanos , Levodopa/uso terapêutico , Pessoa de Meia-Idade , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/psicologia , Índice de Gravidade de Doença , Resultado do Tratamento
13.
PLoS One ; 15(8): e0237328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32790707

RESUMO

α-Synuclein (αSyn) fibrils spread from one neuronal cell to another. This prion-like phenomenon is believed to contribute to the progression of the pathology in Parkinson's disease and other synucleinopathies. The binding of αSyn fibrils originating from affected cells to the plasma membrane of naïve cells is key in their prion-like propagation propensity. To interfere with this process, we designed polypeptides derived from proteins we previously showed to interact with αSyn fibrils, namely the molecular chaperone Hsc70 and the sodium/potassium pump NaK-ATPase and assessed their capacity to bind αSyn fibrils and/or interfere with their take-up by cells of neuronal origin. We demonstrate here that polypeptides that coat αSyn fibrils surfaces in such a way that they are changed affect αSyn fibrils binding to the plasma membrane components and/or their take-up by cells. Altogether our observations suggest that the rationale design of αSyn fibrils polypeptide binders that interfere with their propagation between neuronal cells holds therapeutic potential.


Assuntos
Neurônios/efeitos dos fármacos , Peptídeos/farmacologia , Agregação Patológica de Proteínas/tratamento farmacológico , alfa-Sinucleína/metabolismo , Sequência de Aminoácidos , Amiloide/antagonistas & inibidores , Amiloide/metabolismo , Animais , Linhagem Celular , Proteínas de Choque Térmico HSC70/química , Proteínas de Choque Térmico HSC70/metabolismo , Proteínas de Choque Térmico HSC70/farmacologia , Humanos , Camundongos , Modelos Moleculares , Neurônios/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Peptídeos/química , Príons/antagonistas & inibidores , Príons/metabolismo , Agregados Proteicos/efeitos dos fármacos , Agregação Patológica de Proteínas/metabolismo , ATPase Trocadora de Sódio-Potássio/química , ATPase Trocadora de Sódio-Potássio/metabolismo , ATPase Trocadora de Sódio-Potássio/farmacologia
14.
Medicine (Baltimore) ; 99(27): e20758, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629653

RESUMO

BACKGROUND: Medicines optimisation is important for the management of Parkinson's disease (PD). As many patients with PD have other long-term conditions, treatment is complex and risk of adverse events for these patients is high. OBJECTIVE: To explore the role of pharmacists and impact of pharmacy interventions for PD patients. METHODS: We comprehensively searched PubMed, Embase, the Cochrane Library and Chinese databases Sinomed, China National Knowledge Infrastructure to identify studies reporting pharmacist interventions and pharmacy services for PD patients using a predefined search strategy. The search period was from inception to March 2019. We also manually searched the reference list of included studies and ClinicalTrials.gov. We conducted meta-analyses to synthesize the evidence quantitatively. RESULTS: A total of 1607 studies were identified by applying the search criteria. After screening, 19 cross-sectional and case-controlled studies with 1458 PD patients from 9 countries were included. Pharmacist interventions for PD patients most commonly related to adverse drug reactions (ADRs) (13 studies), adherence assessment (12 studies), medication review (12 studies), identification of drug interactions (11 studies), monitoring response to medication therapy (11 studies), identification of inappropriate medication (11 studies), and patient education (10 studies). Most pharmacy services were provided in outpatient settings (13 studies). Reported impact measures included adherence (8 studies), quality of life (7 studies), and identification of drug-related problems (6 studies) such as ADRs (393 times out of 1760 times, 22.33%, 6 studies), inappropriate drug choice (349 times, 19.83%, 6 studies), inappropriate dosage (335 times, 19.03%, 6 studies), inappropriate drug use (257 times, 14.60%, 3 studies) and drug-drug interactions (146 times, 8.3%, 4 studies). Pooled results from 3 studies indicated no statistically significant impact of pharmacy services on all subscales of PD Questionnaire-39. CONCLUSION: ADRs were the most widely reported drug-related problems for PD patients; pharmacy services may have a role to play in medication adherence but were not found to impact on quality of life.


Assuntos
Antiparkinsonianos/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Assistência Farmacêutica , Antiparkinsonianos/administração & dosagem , Humanos , Farmacêuticos
16.
Cochrane Database Syst Rev ; 7: CD012990, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32700772

RESUMO

BACKGROUND: Parkinson's disease (PD) is a progressive disorder characterised by both motor and non-motor problems. Glucagon-like peptide-1 (GLP-1) receptor agonists, licensed for treatment of type 2 diabetes, work by stimulating GLP-1 receptors in the pancreas, which triggers the release of insulin. GLP-1 receptors have been found in the brain. Insulin signalling in the brain plays a key role in neuronal metabolism and repair and in synaptic efficacy, but insulin signalling is desensitised in the brain of people with PD. Researchers are exploring the neuroprotective effects of GLP-1 receptor agonists in neurodegenerative disorders such as PD. OBJECTIVES: To evaluate the effectiveness and safety of GLP-1 receptor agonists for Parkinson's disease. SEARCH METHODS: We searched the Cochrane Movement Disorders Group trials register; the Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; and Ovid MEDLINE and Embase. We also searched clinical trials registries, and we handsearched conference abstracts. The most recent search was run on 25 June 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults with PD that compared GLP-1 receptor agonists with conventional PD treatment, placebo, or no treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias. We rated the quality of evidence using GRADE. We resolved discrepancies between the two data extractors by consultation with a third review author. MAIN RESULTS: Through our searches, we retrieved 99 unique records, of which two met our inclusion criteria. One double-blind study of exenatide versus placebo randomised 62 participants, who self-administered exenatide or placebo for 48 weeks and were followed up at 60 weeks after a 12-week washout. One single-blind study of exenatide versus no additional treatment randomised 45 participants; participants in the intervention group self-administered exenatide for 12 months, and all participants were followed up at 14 months and 24 months following absence of exenatide for 2 months and 12 months, respectively. These trials had low risk of bias, except risk of performance bias was high for Aviles-Olmos 2013. Exenatide versus placebo Primary outcomes We found low-certainty evidence suggesting that exenatide improves motor impairment as assessed by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in the off-medication state (mean difference (MD) -3.10, 95% confidence interval (CI) -6.11 to -0.09). The difference in scores was slightly greater when scores were adjusted for baseline severity of the condition (as reported by study authors) (MD -3.5, 95% CI -6.7 to -0.3), exceeding the minimum clinically important difference (MCID). We found low-certainty evidence suggesting that exenatide has little or no effect on health-related quality of life (HRQoL) as assessed by the Parkinson's Disease Questionnaire (PDQ)-39 Summary Index (SI) (MD -1.80, 95% CI -6.95 to 3.35), the EuroQol scale measuring health status in five dimensions (EQ5D) (MD 0.07, 95% CI -0.03 to 0.16), or the EQ5D visual analogue scale (VAS) (MD 5.00, 95% CI -3.42 to 13.42). Eight serious adverse events (SAEs) were recorded, but all were considered unrelated to the intervention. Low-certainty evidence suggests that exenatide has little or no effect on weight loss (risk ratio (RR) 1.25, 95% CI 0.89 to 1.76). Exenatide versus no treatment Primary outcomes at 14 months We found very low-certainty evidence suggesting that exenatide improves motor impairment as assessed by MDS-UPDRS Part III off medication (MD -4.50, 95% CI -8.64 to -0.36), exceeding the MCID. We are uncertain whether exenatide improves HRQoL as assessed by the PDQ-39 SI (MD 3.50, 95% CI -2.75 to 9.75; very low-quality evidence). We found very low-certainty evidence suggesting that exenatide has little or no effect on the number of SAEs (RR 1.60, 95% 0.40 to 6.32). We found very low-certainty evidence suggesting that exenatide may lead to weight loss (MD -2.40 kg, 95% CI -4.56 to -0.24). Primary outcomes at 24 months We found evidence as reported by study authors to suggest that exenatide improves motor impairment as measured by MDS-UPDRS Part III off medication (MD 5.6 points, 95% CI 2.2 to 9.0). Exenatide may not improve HRQoL as assessed by the PDQ-39 SI (P = 0.682) and may not result in weight loss (MD 0.1 kg, 95% CI 3.0 to 2.8). AUTHORS' CONCLUSIONS: Low- or very low-certainty evidence suggests that exenatide may improve motor impairment for people with PD. The difference in motor impairment observed between groups may persist for some time following cessation of exenatide. This raises the possibility that exenatide may have a disease-modifying effect. SAEs were unlikely to be related to treatment. The effectiveness of exenatide for improving HRQoL, non-motor outcomes, ADLs, and psychological outcomes is unclear. Ongoing studies are assessing other GLP-1 receptor agonists.


Assuntos
Exenatida/uso terapêutico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Doença de Parkinson/tratamento farmacológico , Viés , Método Duplo-Cego , Exenatida/administração & dosagem , Exenatida/efeitos adversos , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Placebos/administração & dosagem , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Autoadministração , Método Simples-Cego
17.
Life Sci ; 257: 118019, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32629002

RESUMO

Parkinson's disease (PD) is a disease of the human nervous system with an onset, in the sixth and seventh decades of the human life. Chiefly perceived as progressive degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc) with the ensued loss of dopamine in the striatum and the presence of Lewy bodies, consisting of α-synuclein agglomeration. In which the neuronal bridge between substantia nigra and striatum plays an advent role in the motor system. Dilapidation of these neurons results in dopamine depletion which in-turn makes hay to PD. Eventually, the etiology and pathogenesis of PD were still on a hike of dilemma. Traditional Chinese medicine (TCM), including Chinese herbal remedies, acupuncture, and manipulative therapies, is commonly used as an adjunctive therapy in different diseases, particularly neurological diseases, in Asian countries. Additionally, TCM might improve the prognoses and the quality of life of patients with PD because it induces less adverse drug reactions. The present review describes research on the various neuroprotective components and herbal extracts from herbal medicines in the context of addressing the effects of PD.


Assuntos
Medicina Tradicional Chinesa/métodos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/terapia , Animais , Encéfalo/metabolismo , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Parte Compacta da Substância Negra/metabolismo , Substância Negra/efeitos dos fármacos , Tirosina 3-Mono-Oxigenase/metabolismo , alfa-Sinucleína/metabolismo
18.
Expert Opin Pharmacother ; 21(14): 1659-1665, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32640853

RESUMO

INTRODUCTION: Heterogeneity of symptoms and individual variability of progression characterizes Parkinson's disease. Unmet therapeutic needs include a cure, disease modification, and improvement of available marketed dopamine-substituting compounds. Personalized treatment, tailored to the patients' needs and symptoms, aims to ameliorate impaired motor behavior and non-motor features. Injection or infusion of apomorphine is a therapeutic option for more advanced patients with severe levodopa associated motor complications. AREAS COVERED: This narrative review summarizes the subcutaneous administration, efficacy, and side effects of the non-ergot derivative dopamine agonist apomorphine following a non-systematic literature research. EXPERT OPINION: Subcutaneous apomorphine hydrochloride application rapidly terminates intervals with severe motor impairment with bolus injections. Oscillation of motor behavior well responds to continuous apomorphine infusions. Long-term application of the commercially available apomorphine hydrochloride solution sooner or later affects skin and oral mucosa. Onset of skin nodules associated with subcutaneous tissue inflammation probably results from the antioxidant preservative sodium metabisulfite in the apomorphine solution. Addition of another better tolerated and safer antioxidant instead of sodium metabisulphite or use of an already available concentrated apomorphine-free base formulation will enhance its future use, its tolerability, safety, and acceptance of subcutaneous and sublingual application.


Assuntos
Antiparkinsonianos/administração & dosagem , Apomorfina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Doença de Parkinson/tratamento farmacológico , Antiparkinsonianos/efeitos adversos , Antiparkinsonianos/uso terapêutico , Apomorfina/efeitos adversos , Apomorfina/uso terapêutico , Progressão da Doença , Agonistas de Dopamina/efeitos adversos , Agonistas de Dopamina/uso terapêutico , Humanos , Reação no Local da Injeção , Injeções Subcutâneas , Levodopa/administração & dosagem , Levodopa/efeitos adversos , Levodopa/uso terapêutico , Tela Subcutânea/efeitos dos fármacos , Tela Subcutânea/imunologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-32635358

RESUMO

Background: Clinical and epidemiological studies suggest that two of the most common geriatric diseases, type 2 diabetes and Parkinson's disease (PD), are linked. These studies notably suggest that treatment of insulin resistance in type 2 diabetes may beneficially modify the pathophysiology of PD and help to maintain motor and nonmotor function. In this meta-analysis, we evaluate the efficacy of new antidiabetic agents in the treatment of PD. Methods: We systematically searched PubMed, Medline, ProQuest, ScienceDirect, ClinicalKey, and Cochrane Library from the date of their inception until 15 March 2020. Multiple efficacy parameters were compared between treatment groups. The results are expressed as mean differences with 95% confidence intervals (CIs) in a random-effects model. Results: A meta-analysis of the data extracted from three randomized control trials revealed that treatment with exenatide yielded significant improvements in scores on the Unified Parkinson's Disease Rating Scale Part I (UPDRS-I) (-0.438, 95% CI, -0.828 to -0.048, p = 0.028), UPDRS Part IV (UPDRS-IV) (-0.421, 95% CI, -0.811 to -0.032, p = 0.034) and the Mattis Dementia Rating Scale (MDRS) (-0.595, 95% CI, -1.038 to -0.151, p = 0.009). At the 12-month follow-up, the UPDRS Part III (UPDRS-III) scores in the off-medication phase revealed significant improvements in patients using exenatide (-0.729; 95% CI, -1.233 to -0.225, p = 0.005). Treatment with pioglitazone did not yield significant improvements in UPDRS, MDRS, or Parkinson's Disease Questionnaire scores. Conclusion: This meta-analysis suggests that exenatide use is associated with the alleviation of cognitive, motor and nonmotor symptoms. However, long-term studies with a large sample size of patients with PD of varying severity are required.


Assuntos
Hipoglicemiantes/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Idoso , Diabetes Mellitus Tipo 2 , Exenatida , Humanos , Masculino , Resultado do Tratamento
20.
Neurology ; 95(11): e1461-e1470, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32651292

RESUMO

OBJECTIVE: We tested the hypothesis that there are 2 distinct phenotypes of Parkinson tremor, based on interindividual differences in the response of resting tremor to dopaminergic medication. We also investigated whether this pattern is specific to tremor by comparing interindividual differences in the dopamine response of tremor to that of bradykinesia. METHODS: In this exploratory study, we performed a levodopa challenge in 76 tremulous patients with Parkinson tremor. Clinical scores (Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale part III) were collected "off" and "on" a standardized dopaminergic challenge (200/50 mg dispersible levodopa-benserazide). In both sessions, resting tremor intensity was quantified using accelerometry, both during rest and during cognitive coactivation. Bradykinesia was quantified using a speeded keyboard test. We calculated the distribution of dopamine-responsiveness for resting tremor and bradykinesia. In 41 patients, a double-blinded, placebo-controlled dopaminergic challenge was repeated after approximately 6 months. RESULTS: The dopamine response of resting tremor, but not bradykinesia, significantly departed from a normal distribution. A cluster analysis on 3 clinical and electrophysiologic markers of tremor dopamine-responsiveness revealed 3 clusters: dopamine-responsive, intermediate, and dopamine-resistant tremor. A repeated levodopa challenge after 6 months confirmed this classification. Patients with dopamine-responsive tremor had greater disease severity and tended to have a higher prevalence of dyskinesia. CONCLUSION: Parkinson resting tremor can be divided into 3 partially overlapping phenotypes, based on the dopamine response. These tremor phenotypes may be associated with different underlying pathophysiologic mechanisms, requiring a different therapeutic approach.


Assuntos
Antiparkinsonianos/uso terapêutico , Dopaminérgicos/uso terapêutico , Resistência a Medicamentos/efeitos dos fármacos , Levodopa/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Tremor/tratamento farmacológico , Acelerometria , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Resistência a Medicamentos/fisiologia , Feminino , Seguimentos , Humanos , Hipocinesia/diagnóstico por imagem , Hipocinesia/tratamento farmacológico , Hipocinesia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/fisiopatologia , Resultado do Tratamento , Tremor/diagnóstico por imagem , Tremor/fisiopatologia
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