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Abstract Background and objective Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non‐motor, cognition, and dependency) and five stages, correlated with disease severity and patients’ quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. Patients and methods Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross‐sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory‐II (BDI‐II), PQ‐10, and EUROHIS‐QOL 8‐item index (EUROHIS‐QOL8). Results Two hundred and twenty‐four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4–5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p

Introduction. Drooling in Parkinson’s disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results. The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p

Objective: The aim of the present study was to analyze the progression of non-motor symptoms (NMS) burden in Parkinson’s disease (PD) patients regarding the development of motor fluctuations (MF). Methods: PD patients without MF at baseline, who were recruited from January 2016 to November 2017 (V0) and evaluated again at a 2-year follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this analysis. MF development at V2 was defined as a score ≥ 1 in the item-39 of the UPDRS-Part IV, whereas NMS burden was defined according to the Non-motor Symptoms Scale (NMSS) total score. Results: Three hundred and thirty PD patients (62.67 ± 8.7 years old; 58.8% males) were included. From V0 to V2, 27.6% of the patients developed MF. The mean NMSS total score at baseline was higher in those patients who developed MF after the 2-year follow-up (46.34 ± 36.48 vs. 34.3 ± 29.07; p = 0.001). A greater increase in the NMSS total score from V0 to V2 was observed in patients who developed MF (+16.07 ± 37.37) compared to those who did not develop MF (+6.2 ± 25.8) (p = 0.021). Development of MF after a 2-year follow-up was associated with an increase in the NMSS total score (β = 0.128; p = 0.046) after adjustment to age, gender, years from symptoms onset, levodopa equivalent daily dose (LEDD) and the NMSS total score at baseline, and the change in LEDD from V0 to V2. Conclusions: In PD patients, the development of MF is associated with a greater increase in the NMS burden after a 2-year follow-up.

Background and objective: Diplopia is relatively common in Parkinson’s disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it. Patients and Methods: PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as “with diplopia” or “without diplopia” according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls. Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269–4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012–1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson’s Disease Rating Scale–III (OR = 1.039; 95%CI, 1.023–1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001–1.057; p = 0.049) scores were independent factors associated with diplopia (R2 = 0.25; Hosmer and Lemeshow test, p = 0.716). Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Background and objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson’s disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD). Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%. Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen’s effect size = −0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2. Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.

Background: Directional subthalamic stimulation in Parkinson's disease can increase stimulation threshold for adverse effects and widen the therapeutic window. However, selection of programming settings is time consuming, requiring a thorough monopolar clinical review. To overcome this, programming may be guided by intraoperatively recording local field potential beta oscillations (13–35 Hz). Objectives: 1) Evaluate whether the power of beta oscillations recorded intraoperatively can predict the clinically most effective directional contacts; and 2) assess long-term directional stimulation outcomes between patients programmed based on clinical monopolar review and patients programmed based on beta activity. Methods: We conducted a non-randomized, prospective study with 24 Parkinson's disease patients divided into two groups. In group A (14 patients, 2016–2018), we investigated whether beta activity in the directional contacts correlated with clinical efficacy. Stimulating parameters were selected according to clinical monopolar review and mean follow-up was 27 months. In group B (10 patients, 2018–2019), stimulating parameters were selected according to beta activity and mean follow-up was 13 months. Results: Neurophysiological results showed a strong correlation between clinical efficacy and the low-beta sub-band. Contacts with highest beta peaks increased the therapeutic window by 25%. Selecting the two contacts with highest beta peaks provided an 82% probability of selecting the best clinical contact. Clinical results showed similar improvements in group A (motor score, 72% reduction; levodopa-equivalent daily dose, 65% reduction) and B (72% and 63% reduction, respectively), maintained at long-term follow-up. Conclusions: Our results validate the long-term efficacy of directional stimulation guided by intraoperative local field potential beta oscillations.

Objective To explore the experiences of patients suffering from new daily persistent headache (NDPH) regarding the diagnostic process, treatment and medical care.Design A qualitative phenomenological study was conducted.Setting A specialised headache unit at two university hospitals in Spain between February 2017 and December 2018.Participants Patients diagnosed with NDPH according to the International Classification of Headache disorders (third beta edition).Methods Purposeful sampling was performed. Data were collected using unstructured and semistructured interviews, researchers’ field notes and patients’ drawings. An inductive thematic analysis was used to identify significant emerging themes from interviews, field notes and descriptions of patients’ drawings. Also, Guillemin’s proposal was used to analyse the contents of drawings.Results Nineteen patients with a mean age of 45.3 were recruited. Four main themes emerged: (1) Seeking a diagnosis, patients visit many doctors without receiving a clear answer and their diagnosis is delayed; (2) Self-medication—minimising pill intake, medication is ineffective, and therefore, some patients discontinue treatment, or are flexible with how they take medication; (3) Trying other non-pharmacological options, many patients turn to other therapies and complementary and/or alternative therapies as a second option, however these are ineffective and (4) Medical care, with two subthemes, referrals and lacking continuity of care, and building the doctor–patient relationship. Patients describe how the referral breaks the continuity of care, and how they identify the traits of a doctor who is approachable and which behaviours the doctor should avoid when caring for patients.Conclusions An in-depth knowledge of the beliefs and expectations of patients with NDPH will allow the professional to establish a relationship of trust, which will improve the patients’ knowledge of which therapies are the most appropriate, and to establish expectations based on the relationship with the doctor, and not only on patients’ beliefs.

ObjectiveTo investigate the association of pre-existing migraine in patients hospitalised and who recovered from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with the presence of post-coronavirus disease (COVID) symptoms.BackgroundNo study has investigated the role of migraine as a risk factor for development of post-COVID symptoms.MethodsA case-control study including individuals hospitalised during the first wave of the pandemic (from February 20 to May 31, 2020) was conducted. Patients with confirmed previous diagnosis of migraine were considered cases. Two age- and sex-matched individuals without a history of headache per case were also recruited as controls. Hospitalisation/clinical data were collected from hospital medical records. Patients were scheduled for a telephone interview. A list of post-COVID symptoms was systematically evaluated, but participants were invited to freely report any symptom. The Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index were used to assess anxiety/depressive symptoms and sleep quality. Multivariable conditional logistic regression models were constructed.ResultsOverall, 57 patients with confirmed diagnosis of migraine and 144 non-migraine controls who had recovered from COVID-19 were assessed at 7.3 months (SD 0.6) after hospital discharge. The number of post-COVID symptoms in the migraine group was significantly greater (OR 1.70, 95% CI 1.29–2.25, P < 0.001) than in the non-migraine group. Fatigue was significantly more prevalent (OR 2.89, 95% CI 1.32–6.32, P = 0.008) in the migraine group. However, no between-groups difference in the prevalence of headache as a post-COVID symptom was detected.ConclusionPatients with a history of migraine who recovered from COVID-19 exhibited more long-term fatigue as post-COVID sequelae than those without migraine. Some of the pathophysiological changes associated with migraine could predispose to the occurrence of post-COVID symptoms.

We compared the prevalence of musculoskeletal post-COVID pain between previously hospitalized COVID-19 survivors infected with the historical, Alpha or Delta SARS-CoV-2 variant. Data about musculoskeletal post-COVID pain were systematically collected through a telephone interview involving 201 patients who had survived the historical variant, 211 who had survived the Alpha variant and 202 who had survived the Delta variant six months after hospital discharge. Participants were recruited from non-vaccinated individuals hospitalized due to SARS-CoV-2 infection in one hospital of Madrid (Spain) during three different waves of the pandemic (historical, Alpha or Delta variant). Hospitalization and clinical data were collected from hospital medical records. In addition, anxiety/depressive levels and sleep quality were also assessed. The prevalence of musculoskeletal post-COVID pain was higher (p = 0.003) in patients infected with the historical variant (47.7%) than in those infected with the Alpha (38.3%) or Delta (41%) variants. A significantly (p = 0.002) higher proportion of individuals infected with the historical variant reported generalized pain (20.5%) when compared with those infected with the other variants. The prevalence of new-onset post-COVID musculoskeletal pain reached 80.1%, 75.2% and 79.5% of patients infected with the historical, Alpha or Delta variants, respectively. No specific risk factors for developing post-COVID pain were identified depending on the SARS-CoV-2 variant. In conclusion, this study found that musculoskeletal post-COVID pain is highly prevalent in COVID-19 survivors six months after hospital discharge, with the highest prevalence and most generalized pain symptoms in individuals infected with the historical variant. Approximately 50% developed “de novo” post-COVID musculoskeletal pain symptoms.