RESUMO
Aberrant brain oscillations are a hallmark of Parkinson's disease (PD) pathophysiology and may be related to both motor and nonmotor symptoms. Mild cognitive impairment (MCI) affects many people with PD even at the time of diagnosis and conversion risks to PD dementia (PDD) are very high. Unfortunately, pharmacotherapies are not addressing cognitive symptoms in PD. Profiling PD cognitive phenotypes (e.g., MCI, PDD, etc.) may therefore help inform future treatments. Neurophysiological methods, such as magnetoencephalography (MEG), offer the advantage of observing oscillatory patterns, whose regional and temporal profiles may elucidate how cognitive changes relate to neural mechanisms. We conducted a resting-state MEG cross-sectional study of 89 persons with PD stratified into three phenotypic groups: normal cognition, MCI, and PDD, to identify brain regions and frequencies most associated with each cognitive profile. In addition, a neuropsychological battery was administered to assess each domain of cognition. Our data showed higher power in lower frequency bands (delta and theta) observed along with more severe cognitive impairment and associated with memory, language, attention, and global cognition. Of the total 119 brain parcels assessed during source analysis, widespread group differences were found in the beta band, with significant changes mostly occurring between the normal cognition and MCI groups. Moreover, bilateral frontal and left-hemispheric regions were particularly affected in the other frequencies as cognitive decline becomes more pronounced. Our results suggest that MCI and PDD may be qualitatively distinct cognitive phenotypes, and most dramatic changes seem to have happened when the PD brain shows mild cognitive decline.NEW & NOTEWORTHY Can we better stage cognitive decline in patients with Parkinson's disease (PD)? Here, we provide evidence that mild cognitive impairment, rather than being simply a milder form of dementia, may be a qualitatively distinct phase in its development. We suggest that the most dramatic neurophysiological changes may occur during the time the PD brain transitions from normal cognition to MCI, then compensatory changes further occur as the brain "switches" to a dementia state.
Assuntos
Ondas Encefálicas/fisiologia , Disfunção Cognitiva/fisiopatologia , Conectoma , Progressão da Doença , Magnetoencefalografia , Doença de Parkinson/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicaçõesRESUMO
BACKGROUND: Postoperative nausea and vomiting (PONV) is common after tonsillectomy in children. There is evidence that perioperative acupuncture at the pericardium 6 (P6) point is effective for preventing PONV in adults. Our goal was to determine if intraoperative acupuncture at the P6 point, in addition to usual antiemetics, is more effective than antiemetics alone in preventing PONV in children. METHODS: In a randomized double-blind trial, 161 children age 3 through 9 years undergoing tonsillectomy with or without adenoidectomy were randomized to either bilateral acupuncture at P6 plus antiemetics (n = 86) or antiemetics only (n = 75). All participants received ondansetron 0.15 mg/kg and dexamethasone 0.25 mg/kg, up to 10 mg. The presence of nausea, retching, emesis and administration of additional antiemetics were recorded during phases I and II of PACU recovery. Follow-up calls occurred on postoperative day 1 (POD 1). RESULT: During phase I and II recovery, the incidence of PONV was significantly less with acupuncture than without (7.0% vs 34.7%, RR: 0.2, 95% CI: 0.09-0.46; P < 0.001). The difference in PONV was driven by less nausea in the acupuncture group (5.0% vs 24.0%), with no difference in vomiting between the two groups. In the first 24 hours, PONV occurred in 36.1% with acupuncture and 49.3% without; these values did not differ significantly (P = 0.09). CONCLUSIONS: Children receiving acupuncture plus antiemetic therapy had less risk of developing nausea during phase I and II recovery, but there was no difference in PONV on POD 1. Acupuncture may reduce nausea in the PACU, even when combined with antiemetics.
Assuntos
Terapia por Acupuntura , Antieméticos/uso terapêutico , Náusea e Vômito Pós-Operatórios/prevenção & controle , Pontos de Acupuntura , Adenoidectomia , Criança , Pré-Escolar , Terapia Combinada , Dexametasona/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Incidência , Masculino , Ondansetron/uso terapêutico , Náusea e Vômito Pós-Operatórios/epidemiologia , Tonsilectomia , Resultado do TratamentoRESUMO
CONTEXT: Parkinson's disease and related disorders (PDRD) are fatal neurodegenerative disorders characterized by a fluctuating course that can complicate prognostication. The "surprise question" (SQ: "Would you be surprised if your patient died in the next year?") has been used to identify patients with limited prognosis but has not been assessed in PDRD. OBJECTIVES: To determine the validity of the SQ in predicting 12-month mortality in PDRD. METHODS: Data was analyzed from 301 patients and 34 community-based neurologists who were participating in a clinical trial of outpatient palliative care for patients with PDRD. Clinicians answered the SQ for each patient at baseline. Descriptive statistics at baseline, chi-square tests of independence, 2 × 2 and 2 × 3 cross tables were used. Survival analysis compared SQ responses using Kaplan-Meier curves. Risk estimate analyses identified patient characteristics associated with clinicians' responses. RESULTS: Mortality was 10.3% (N = 31) at 1 year. The sensitivity and specificity of the SQ was 80.7% and 58.9%, respectively with AUC = 0.70, positive predictive value of 18.4% and negative predictive value of 96.4%. Older age, atypical parkinsonism, and dementia were associated with responding "no" to the SQ. CONCLUSION: The SQ is sensitive to 12-month mortality in PDRD, with a high negative predictive value. The SQ may be useful for identifying patients less likely to die within a year and may be useful for identifying patients with palliative care needs outside of end-of-life care. This latter use may assist in mobilizing early and timely referral to specialist palliative care.
Assuntos
Doença de Parkinson , Assistência Terminal , Humanos , Doença de Parkinson/diagnóstico , Doença de Parkinson/terapia , Estudos Prospectivos , Cuidados Paliativos , Medição de Risco , PrognósticoRESUMO
Importance: Parkinson disease and related disorders (PDRD) are the fastest growing neurodegenerative illness in terms of prevalence and mortality. As evidence builds to support palliative care (PC) for PDRD, studies are needed to guide implementation. Objective: To determine whether PC training for neurologists and remote access to a PC team improves outcomes in patients with PDRD in community settings. Design, Setting, and Participants: This pragmatic, stepped-wedge comparative effectiveness trial enrolled and observed participants from 19 community neurology practices supported by PC teams at 2 academic centers from March 8, 2017, to December 31, 2020. Participants were eligible if they had PDRD and moderate to high PC needs. A total of 612 persons with PDRD were referred; 253 were excluded. Patients were excluded if they had another diagnosis meriting PC, were receiving PC, or were unable or unwilling to follow study procedures. Patients received usual care or the intervention based on when their community neurologist was randomized to start the intervention. Data were analyzed from January 2021 to September 2023. Intervention: The intervention included (1) PC education for community neurologists and (2) team-based PC support via telehealth. Main Outcomes and Measures: The primary outcomes were differences at 6 months in patient quality of life (QOL; measured by the Quality of Life in Alzheimer Disease Scale [QOL-AD]) and caregiver burden (Zarit Burden Interview) between the intervention and usual care. Results: A total of 359 patients with PDRD (233 men [64.9%]; mean [SD] age, 74.0 [8.8] years) and 300 caregivers were enrolled. At 6 months, compared with usual care, participants receiving the intervention had better QOL (QOL-AD score, 0.09 [95% CI, -0.63 to 0.82] vs -0.88 [95% CI, -1.62 to -0.13]; treatment effect estimate, 0.97; 95% CI, 0.07-1.86; P = .03). No significant difference was observed in caregiver burden (Zarit Burden Interview score, 1.19 [95% CI, 0.16 to 2.23] vs 0.55 [95%, -0.44 to 1.54]; treatment effect estimate, 0.64; 95% CI, -0.62 to 1.90; P = .32). Advance directive completion was higher under the intervention (19 of 38 [50%] vs 6 of 31 [19%] among those without directives at the beginning of the study; P = .008). There were no differences in other outcomes. Conclusions and Relevance: PC education for community neurologists and provision of team-based PC via telehealth is feasible and may improve QOL and advance care planning. Overall treatment effects were small and suggest opportunities to improve both the intervention and implementation. Trial Registration: ClinicalTrials.gov Identifier: NCT03076671.
Assuntos
Doença de Parkinson , Telemedicina , Masculino , Humanos , Idoso , Qualidade de Vida , Doença de Parkinson/terapia , Neurologistas , Cuidados Paliativos/métodos , Telemedicina/métodosRESUMO
Introduction: Cognitive impairment is a highly prevalent non-motor feature of Parkinson's disease (PD). A better understanding of the underlying pathophysiology may help in identifying therapeutic targets to prevent or treat dementia. This study sought to identify metabolic alterations in the prefrontal cortex (PFC), a key region for cognitive functioning that has been implicated in cognitive dysfunction in PD. Methods: Proton Magnetic Resonance Spectroscopy was used to investigate metabolic changes in the PFC of a cohort of cognitively normal individuals without PD (CTL), as well as PD participants with either normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD). Ratios to Creatine (Cre) resonance were obtained for glutamate (Glu), glutamine and glutamate combined (Glx), N-acetylaspartate (NAA), myoinositol (mI), and total choline (Cho), and correlated with cognitive scores across multiple domains (executive function, learning and memory, language, attention, visuospatial function, and global cognition) administered to the PD participants only. Results: When individuals retain cognitive capabilities, the presence of Parkinson's disease does not create metabolic disturbances in the PFC. However, when cognitive symptoms are present, PFC Glu/Cre ratios decrease with significant differences between the PD-NC and PPD groups. In addition, Glu/Cre ratios and memory scores were marginally associated, but not after Bonferroni correction. Conclusion: These preliminary findings indicate that fluctuations in prefrontal glutamate may constitute a biomarker for the progression of cognitive impairments in PD. We caution for larger MRS investigations of carefully defined PD groups.
RESUMO
BACKGROUND: Myringotomy tube placement is a pediatric procedure frequently performed under inhalational anesthesia without intravenous line placement. Emergence delirium is common following sevoflurane anesthesia, and can lead to patient harm and escalation of nursing care. Our goal was to determine if intraoperative acupuncture, compared to standard of care, reduces emergence delirium in children undergoing myringotomy tube placement. METHODS: Single center, randomized, controlled trial at a university hospital, including children ages 1-6 years with ASA physical status 1-3 scheduled for myringotomy tube placement. Participants were stratified based on midazolam premedication and randomized to intraoperative acupuncture (AC, N.=49) or standard anesthesia care (SC, N.=50). Acupuncture needles were placed in bilateral Heart 7 (HT7) and ear Shen Men points after anesthesia induction. A blinded observer in the PACU assessed emergence delirium using the Pediatric Anesthesia Emergence Delirium (PAED) scale. Endpoints were highest PAED score in the recovery room and post-discharge agitation and sleep quality. RESULTS: Patient baseline characteristics were similar between treatment groups. With midazolam premedication, the highest PAED score was 11.6 in patients receiving AC and 12.0 for SC. Without midazolam premedication, the highest PAED was 11.8 in patients receiving AC and 10.7 for SC. The overall PAED score difference between AC and SC groups was 0.33 (95% CI -1.5, 2.2, P=0.723). CONCLUSIONS: Intraoperative acupuncture at HT7 and ear Shen Men did not reduce PAED scores after myringotomy tube placement. Based on these data, it is therefore unlikely that a larger study of the same design would demonstrate a significant effect of intraoperative acupuncture on emergence delirium after brief sevoflurane anesthesia. However, other acupuncture points or techniques could be considered.