Effects of deep brain stimulation and verbal suggestions on pain in Parkinson's disease.

BACKGROUND AND OBJECTIVES: In Parkinson's disease (PD) patients, verbal suggestions have been shown to modulate motor and clinical outcomes in treatment with subthalamic deep brain stimulation (DBS). Furthermore, DBS may alleviate pain in PD. However, it is unknown if verbal suggestions influence DBS' effects on pain. METHODS: Twenty-four people with PD and DBS had stimulation downregulated (80-60 to 20%) and upregulated (from 20-60 to 80%) in a blinded manner on randomized test days: (1) with negative and positive suggestions of pain for down- and upregulation, respectively, and (2) with no suggestions to effect (control). Effects of DBS and verbal suggestions were assessed on ongoing and evoked pain (hypertonic saline injections) via 0-10 numerical rating scales along with motor symptoms, expectations, and blinding. RESULTS: Stimulation did not influence ongoing and evoked pain but influenced motor symptoms in the expected direction. Baseline and experimental pain measures showed no patterns in degree of pain. There was a trend toward negative suggestions increasing pain and positive suggestions decreasing pain. Results show significant differences in identical stimulation with negative vs positive suggestions (60% conditions AUC 38.75 vs 23.32, t(13) = 3.10, p < 0.001). Expectations to pain had small to moderate effects on evoked pain. Patients estimated stimulation level correctly within 10 points. CONCLUSION: Stimulation does not seem to influence ongoing and evoked pain, but verbal suggestions may influence pain levels. Patients appear to be unblinded to stimulation level which is an important consideration for future studies testing DBS in an attempted blind fashion.

Prevalence and severity of freezing of gait in a Danish cohort of people with Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) is a widespread neurodegenerative disorder characterised by wide range of symptoms. Freezing of gait (FoG), a transient feeling that the patient's feet are nailed to the floor, resulting in an inability to move, is a particularly distressful symptom. The assessment of FoG can be challenging. Often, clinicians are reliant on patients' subjective experiences and patient questionnaires such as the Freezing of Gait Questionnaire (FOGQ) and its updated version, the New FOGQ (NFOGQ).Until now, the NFOGQ has not been validated and piloted for use in Danish. Therefore, few attempts have been made to assess the prevalence and severity of FoG in Danish patients with PD. METHODS: This report describes a two-step process of adapting the NFOGQ into Danish and piloting its use among a cohort of patients with PD. A satisfactory translation (Danish NFOGQ) was produced and successfully piloted. RESULTS: The translation showed robust test-retest reliability after two weeks. Patients fully understood the questionnaire. Using the Danish NFOGQ in an online prevalence survey, we found that 35.7% of respondents had experienced FoG and that the prevalence correlated with disease duration. CONCLUSION: The Danish NFOGQ appears to be appropriate for assessing FoG in Danish patients with PD in both clinical and research settings. FUNDING: None. TRIAL REGISTRATION: Not relevant.

The prognostic significance of biomarkers in cerebrospinal fluid following severe traumatic brain injury: a systematic review and meta-analysis.

After severe traumatic brain injury (sTBI) proteins, neurotrophic factors and inflammatory markers are released into the biofluids. This review and meta-analysis searched the literature for prognostic candidate cerebrospinal fluid markers and their relation to sTBI patient outcome. A systematic search of the literature was carried out across PubMed, EMBASE, PubMed Central (PMC), and Cochrane Central Library. Biomarker concentrations were related to the Glasgow Outcome Scale dichotomized into favorable and unfavorable outcomes. When a biomarker was reported in ≥ 3 studies, it was included in meta-analysis. The search returned 1527 articles. After full-text analysis, 54 articles were included, 34 from the search, and 20 from the reference lists. Of 9 biomarkers, 8 were significantly different compared to controls (IL-4, IL-6, IL-8, IL-10, TNFα, sFas, BDNF, and cortisol). Of these, 5 were significantly increased in sTBI patients with unfavorable outcome (IL-6, IL-8, IL-10, TNFα, and cortisol), compared to patients with favorable outcome. This review demonstrated a correlation between 5 biomarkers and clinical outcome in sTBI patients. The paucity of included studies, however, makes it difficult to extrapolate further on this finding.

Interventions to improve gait in Parkinson's disease: a systematic review of randomized controlled trials and network meta-analysis.

INTRODUCTION: Disabling gait symptoms, especially freezing of gait (FoG), represents a milestone in the progression of Parkinson's disease (PD). This systematic review and network meta-analysis assessed and ranked interventions according to their effectiveness in treating gait symptoms in people with PD across four different groups of gait measures. METHODS: A systematic search was carried out across PubMed, EMBASE, PubMed Central (PMC), and Cochrane Central Library from January 2000 to April 2021. All interventions, or combinations, were included. The primary outcome was changes in objective gait measures, before and after intervention. Outcome measures in the included studies were stratified into four different types of gait outcome measures; dynamic gait, fitness, balance, and freezing of gait. For the statistical analysis, five direct head-to-head comparisons of interventions, as well as indirect comparisons were performed. Corresponding forest plots ranking the interventions were generated. RESULTS: The search returned 6288 articles. From these, 148 articles could be included. Of the four different groups of measurement, three were consistent, meaning that there was agreement between direct and indirect evidence. The groups with consistent evidence were dynamic gait, fitness, and freezing of gait. For dynamic gait measures, treatments with the largest observed effect were Aquatic Therapy with dual task exercising (SMD 1.99 [- 1.00; 4.98]) and strength and balance training (SMD 1.95 [- 0.20; 4.11]). For measures of fitness, treatments with the largest observed effects were aquatic therapy (SMD 3.41 [2.11; 4.71] and high-frequency repetitive transcranial magnetic stimulation (SMD 2.51 [1.48; 3.55]). For FoG measures, none of the included interventions yielded significant results. CONCLUSION: Some interventions can ameliorate gait impairment in people with PD. No recommendations on a superior intervention can be made. None of the studied interventions proved to be efficacious in the treatment of FoG. PROSPERO (registration ID CRD42021264076).

Active case-finding of tuberculosis in general populations and at-risk groups: a systematic review and meta-analysis.

BACKGROUND: The World Health Organization (WHO) recommends active case-finding (ACF) of tuberculosis (TB) in certain high-risk groups; however, more evidence is needed to elucidate the scope of ACF beyond the current recommendations. In this study we aimed to systematically review yields (the prevalence of active TB) of studies on ACF in general populations and at-risk groups. METHODS: A literature search in PubMed, Embase and the Cochrane Central Library (CENTRAL) was performed for studies concluded after 31 December 1999 and published before 1 September 2020. Screening yields were estimated and yield/prevalence ratios (ratio between yield of study and WHO estimated prevalence of TB) were calculated to assess which groups might especially benefit from ACF. Finally, risk of bias was assessed and heterogeneity was investigated using meta-regression and sensitivity analyses. RESULTS: We included 197 studies, with a total of 12 372 530 screened and 53 158 cases found. Yields were high among drug users, close contacts, the poor and marginalised, people living with HIV, and prison inmates across incidence strata, and estimated yield/prevalence ratios in screenings of general populations tended to be >1 with an overall ratio of 1.4 and ranging between 1.0 and 1.5. Sensitivity analyses suggested that inclusion of studies at high risk of bias contributed to underestimation of yields. CONCLUSION: Despite many studies using insensitive screening methods, these results suggest that more at-risk groups should be considered for inclusion in future screening recommendations and that screening of general populations may outperform current case-finding practices, providing evidence for extending ACF beyond the current recommendations.