Staging Parkinson's Disease Combining Motor and Nonmotor Symptoms Correlates with Disability and Quality of Life.

INTRODUCTION: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage. MATERIALS AND METHODS: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale. RESULTS: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB (p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively (p < 0.005; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001). CONCLUSION: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden.

Depression is Associated with Impulse-compulsive Behaviors in Parkinson's disease.

BACKGROUND: Depression and impulse control disorders (ICDs) are both common in Parkinson's disease (PD) patients and their coexistence is frequent. Our aim was to determine the relationship between depression and impulsive-compulsive behaviors (ICBs) in a large cohort of PD patients. METHODS: PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were included in the study. The QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale) was used for screening ICDs (cutoff points: gambling ≥6, buying ≥8, sex≥8, eating≥7) and compulsive behaviors (CBs) (cutoff points: hobbyism-punding ≥7). Mood was assessed with the BDI-II (Beck Depression Inventory - II) and major, minor, and subthreshold depression were defined. RESULTS: Depression was more frequent in PD patients with ICBs than in those without: 66.3% (69/104) vs 47.5% (242/509); p<0.0001. Major depression was more frequent in this group as well: 22.1% [23/104] vs 14.5% [74/509]; p=0.041. Considering types of ICBs individually, depression was more frequent in patients with pathological gambling (88.9% [8/9] vs 50.2% [303/603]; p=0.021), compulsive eating behavior (65.9% [27/41] vs 49.7% [284/572]; p=0.032), and hobbyism-punding (69% [29/42] vs 49.4% [282/571]; p=0.010) than in those without, respectively. The presence of ICBs was also associated with depression (OR=1.831; 95%CI 1.048-3.201; p=0.034) after adjusting for age, sex, civil status, disease duration, equivalent daily levodopa dose, antidepressant treatment, Hoehn&Yahr stage, non-motor symptoms burden, autonomy for activities of daily living, and global perception of QoL. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Depression is associated with ICBs in PD. Specifically, with pathological gambling, compulsive eating behavior, and hobbyism-punding.

Mood in Parkinson's disease: From early- to late-stage disease.

BACKGROUND: Although depression is known to be frequent in Parkinson's disease (PD), it is unclear how mood can change and/or impact on patient's quality of life (QoL) over time. Our aim was to analyze the frequency of depression, mood related factors and the contribution of mood to a patient's QoL perception in regard to disease duration. METHODS: PD patients recruited from the COPPADIS cohort from January 2016 to November 2017 were included in this cross-sectional study. Three groups were defined: <5 years (Group A); from 5 to <10 years (Group B); ≥10 years (Group C). Analysis with well-planned linear regression models was conducted to determine how different factors contribute to mood (Beck Depression Inventory-II [BDI-II] as dependent variable), to health-related QoL (39-item Parkinson's Disease Questionnaire [PDQ-39SI] as dependent variable) and to global QoL (European Health Interview Survey - Quality of Life Eight-Item Index [EUROHIS-QOL8] as dependent variable). RESULTS: Six hundred and sixty-three PD patients (62.6 ± 8.9 years old, 59.6% males) were included: Group A, 50.1% (n = 332); Group B, 33.3% (n = 221) and Group C, 16.6% (n = 110). There were no differences between the three groups in terms of the frequency of depressive symptoms nor the frequency of depression type (major vs. minor vs. subthreshold) (p = 0.729). However, the unique percent variance of PDQ-39SI and EUROHIS-QOL8 explained by BDI-II total score was 2 (23.7%) and threefold (26.9%), respectively, in Group C compared to the other two groups. EUROHIS-QOL8 total score provided the highest unique contribution to mood (16.8%). CONCLUSIONS: Although depression-type frequency does not appear to change over time in PD; the contribution of mood on QoL perception is greater in patients with longer disease duration.

High ultrasensitive serum C-reactive protein may be related to freezing of gait in Parkinson's disease patients.

C-reactive protein (CRP) is a biomarker of systemic inflammation that has been linked to accelerated decline in walking speed in older adults. The aim of the present study was to compare the CRP levels of PD patients with vs patients without freezing of gait (FOG). Patients and controls participating in the COPPADIS-2015 study that performed blood extraction for determining molecular serum biomarkers were included. Patients with FOG were identified as those with a score of 1 or greater on item-3 of the Freezing of Gait Questionnaire (FOG-Q). Immunoassay was used for determining ultrasensitive CRP (US-CRP) level (mg/dL). In the PD group (n = 225; 61.8 ± 9.5 years old, 61.8% males), 32% of the patients presented FOG but none in the control group (n = 65; 60.3 ± 6.1 years old, 56.9% males) (p < 0.0001). Differences in US-CRP level were significant in patients with FOG vs patients without FOG and vs controls (0.31 ± 0.52 vs 0.16 ± 0.21 vs 0.21 ± 0.22; p = 0.04). Significant differences were also observed between patients with vs without FOG (p = 0.001) but not between patients and controls (p = 0.163). US-CRP level was related to FOG (OR = 4.369; 95% CI 1.105-17.275; p = 0.036) along with H&Y (OR = 2.974; 95% CI 1.113-7.943; p = 0.030) and non-motor symptoms burden (NMSS total score; OR = 1.017; 95% CI 1.005-1.029; p = 0.006) after adjusting for age, gender, disease duration, equivalent daily levodopa dose, number of non-antiparkinsonian drugs per day, motor fluctuations, cognition, motor phenotype, and chronic use of anti-inflammatory drugs. The present study suggests that serum US-CRP level is related to FOG in PD patients. Inflammation could be linked to FOG development.

COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015): an ongoing global Parkinson's disease project about disease progression with more than 1000 subjects included. Results from the baseline evaluation.

BACKGROUND AND PURPOSE: In Parkinson's disease (PD), the course of the disorder is highly variable between patients. Well-designed, prospective studies for identifying PD progression biomarkers are necessary. Our aim was to show the results of baseline evaluations of an ongoing global PD project, COPPADIS-2015 (Cohort of Patients with PArkinson's DIsease in Spain, 2015). METHODS: This was an observational, descriptive, nationwide study (Spain). The recruitment period ended in October 2017. Baseline evaluation included more than 15 validated scales and complementary studies in a subgroup of participants. RESULTS: In total, 1174 subjects from 35 centres were considered valid for baseline analysis: 694 patients (62.6 ± 8.9 years old, 60.3% males), 273 caregivers (58.5 ± 11.9 years old, 31.8% males) and 207 controls (61 ± 8.3 years old, 49.5% males). The mean disease duration was 5.5 ± 4.4 years. Hoehn and Yahr stage was 1 or 2 in 90.7% of the patients whilst 33.9% and 18.1% of them presented motor fluctuations and dyskinesias, respectively. The mean Non-Motor Symptoms Scale total score was 45.4 ± 38.1, and 30.4% of the patients presented cognitive impairment, 16.1% major depression, 12.7% impulse control disorder, 7.2% compulsive behaviour, 57.2% pain and 13.2% falls. Compared to the control group, PD patients presented a significantly higher burden of non-motor symptoms and a worse quality of life. More than 300 subjects conducted complementary studies (serum biomarkers, genetic and neuroimaging). CONCLUSIONS: Parkinson's disease is a complex disorder and different non-motor symptoms are frequently present and are more prevalent than in controls. In real clinical practice it is important to ask for them.

Kinetic behavior of light emission in cholesteric liquid crystal lasers: An experimental study.

Some dynamical aspects of fluorescence and lasing have been studied in a dye-doped cholesteric liquid crystal by measuring the response of the material to nanosecond optical pumping. It has been found that as the pumping energy is increased the fluorescence pulse duration decreases, reaching a minimum at the lasing threshold. Above the threshold the temporal profiles are irregular and consist of a set of narrow pulses whose measured duration is limited by the detector risetime (1 ns). The results are interpreted in terms of a recently proposed model [JETP, 118, 822 (2014)] that makes use of rate equations to account for the laser generation in cholesteric liquid crystals. The prediction of such equations for an experimental configuration appropriate for fluorescence lifetime measurements is analyzed.

Thermally induced light-scattering effects as responsible for the degradation of cholesteric liquid crystal lasers.

We have studied the degradation process of the laser emission in a cholesteric liquid crystal laser. We have found that there exists a negative correlation between the laser efficiency and the amount of light scattered by the liquid-crystal sample in the illuminated area. The growth of scattering is attributed to the appearance of small imperfections generated in the sample as a result of certain thermal processes that involve the dye molecules. The scattering implies an increase of the coefficient of distributed losses, which is the main response of the rise of the laser threshold.

Tratamiento quirúrgico en malformación de chiari I en la edad pediátrica: estudio y resultados en serie de 57 casos / Surgical treatment in chiari I malformation in the pediatric age: study and results in a series of 57 cases

Introducción: Las malformaciones de Chiari constituyen un grupo heterogéneo de patologías que ocasionan la herniación descendente de estructuras de la fosa posterior. La malformación de Chiari tipo I (MCI) se define como la herniación amigdalina de al menos 3 a 5 mm por debajo del nivel del foramen magno. La resonancia magnética ha aumentado el número de casos diagnosticados, inclusive en la edad pediátrica. Este trabajo tiene por objetivo presentar los resultados en cuanto a hallazgos clínicos y evolución postoperatoria en una serie pediátrica y se realiza una revisión del tema. Pacientes y métodos: Se efectuó un análisis retrospectivo de cohorte única de 57 pacientes operados a lo largo de 20 años por el mismo equipo neuroquirúrgico. Se revisaron los registros de uno de los autores (ES) para obtener datos sobre presentación clínica, diagnóstico, tratamiento y evolución postoperatoria, con un seguimiento de al menos 6 meses en cada paciente. Resultados: Se operaron 57 pacientes de entre 3 a 13 años de edad. El 100% de las malformaciones de Chiari I operadas eran sintomáticas. El síntoma más frecuente fue la cefalea (90%). En todos los casos se efectuó descompresión de la fosa posterior con duroplastia. El 100% de los pacientes presentaron mejoría clínica postoperatoria que se mantuvo a los 6 meses de seguimiento. Se registraron 3 casos de pseudomeningocele y un solo caso de fístula externa de LCR (7%). Conclusiones: La descompresión de fosa posterior con duroplastia es una opción quirúrgica muy efectiva y con baja tasa de complicaciones.

Introduction: Chiari malformations constitute a heterogeneous group of disorders characterized by a maldevelopment of the hindbrain and posterior cranial fossa that determines downward herniation of the cerebellar tonsils. Chiari malformation type I is defined as a 3 to 5 mm tonsillar herniation below the level of the foramen magnum. MRI has increased the number of cases diagnosed even in the pediatric age. Hence, the aim of this article is to present our results concerning clinical findings and outcomes on an exclusively pediatric series and to perform a review of the subject.Patients and methods:this is a retrospective, single-cohort study involving 57 patients operated in a 20-year period by the same neurosurgical team. Clinical records of one of the authors (ES) were reviewed in order to obtain data about symptoms, diagnosis, treatment and postoperative outcome at 6-month follow up.Results: 57 patients between 3 and 13 years of age were operated on. All of the patients were symptomatic at the time of diagnosis. The most frequent symptom was headache (90. All of the patients underwent posterior fossa decompression with duroplasty. 100% of the patients experienced sustained clinical improvement even at 6 month-follow up. Three cases of pseudomeningocele and only one case of external CSF leak were observed (7%).Conclusions:according to our findings and international literature, posterior fossa decompression with duroplasty is an effective surgical treatment with a low rate of complications.

Reduced serum progranulin level might be associated with Parkinson's disease risk.

BACKGROUND AND PURPOSE: Common genetic variants (rs5848 and rs646776) have been reported as regulators of blood progranulin (GRN) levels in healthy individuals. METHODS: To assess the influence of rs5848 and rs646776 polymorphisms in both serum GRN level and risk for common neurodegenerative diseases, we studied 304 patients with Parkinson's disease (PD), 217 individuals with Alzheimer's disease, 131 subjects with mild cognitive impairment, and 126 controls. RESULTS: The mean concentration of GRN in the serum of patients with PD (319.6 ng/ml) was significantly lower than that of controls (371.5 ng/ml; P = 0.009), whereas there were no significant differences between other groups. Rs646776 minor allele carriers had lower serum GRN levels in each of the four subgroups. There was no correlation between rs5848 genotypes and serum GRN concentrations. Genotype frequencies of both polymorphisms did not differ between groups. CONCLUSION: Reduced circulating GRN levels might be associated with PD risk by pathogenic factors different from rs5848 and rs646776 polymorphisms.

An assessment of wall motion, perfusion and glucose metabolism in recent myocardial infarction: a comparison in patients with and without revascularization.

The aim of this study was to compare the extent and severity of wall motion abnormalities, perfusion and glucose metabolism, in recent myocardial infarction in patients with and without revascularization. Forty-nine patients were studied (82% men; mean age 58 years) by using echocardiography, 201Tl single photon emission computed tomography (SPECT) rest and redistribution, and 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG) SPECT at a mean of 9.2 days (range, 1-24 days) after myocardial infarction. Twenty-seven of the 49 patients underwent revascularization while the other 22 received medical therapy before echocardiography and studies using radionuclides. A contrast angiogram was obtained for each patient. A follow-up echocardiogram at 3 months was obtained for 44 patients. Images were read blindly, using a 17 segment model, with semi-quantitative analysis. In the whole group, the extent of hypokinesia was 15%+/-14 (mean+/-SD); the extent of mild defects was determined as 5%+/-6 by using 201Tl at rest, 6%+/-9 by using 201Tl redistribution, and 4%+/-6 by using 18F-FDG (P<0.0005, echocardiogram/radionuclides). Echocardiography showed that the extent of akinesia-dyskinesia was 16%+/-18 in revascularized patients and 28%+/-18 in non-revascularized patients (P=0.017). With regard to moderate and severe defects, 201Tl rest showed 19%+/-16 and 28%+/-17, respectively (P=0.047); 201Tl redistribution 17%+/-15 and 26%+/-15, respectively (P=0.043); and 18F-FDG 17%+/-13 and 24%+/-15, respectively (NS). In echocardiography, the extent of hypokinetic segments decreased from 16%+/-15 at baseline to 10%+/-11 at 3 months (P=0.045), in revascularized patients. It is concluded that, in recent myocardial infarction, hypokinesia extent on echocardiogram is greater than mild perfusion or metabolic defect extent, reflecting stunning and so the use of radionuclide techniques appear more accurate for defining the extent of myocardial infarction. Non-revascularized patients showed a significantly greater extent of akinesia-dyskinesia and moderate-severe perfusion defects than did revascularized patients, which can be considered a result of therapy. It is suggested that 201Tl rest perfusion be used for the assessment of myocardial infarction soon after revascularization.

Resultados clínicos de la resincronización ventricular en pacientes con insuficiencia cardíaca severa / Results of intraventricular resynchronization in patients with severe cardiac failure

BACKGROUND: Intraventricular resynchronization with pacemakers is a promising therapy for patients with refractory cardiac failure and intraventricular conductions delay. However its long term effects are not well known. AIM: To report the results of this therapy in patients with cardiac failure. PATIENTS AND METHODS: Fourteen patients (11 male), whose mean age was 68 years, with a severe and refractory cardiac failure, have been treated in our unit using intraventricular resynchronization with pacemakers. Eight had a coronary heart disease and six a dilated myocardiopathy. The pacemaker was implanted transvenously, with conventional stimulation in atrium and right ventricle. The left ventricle was stimulated through an epicardial vein, accessed through the coronary sinus. RESULTS: In one patient the high thresholds did not allow a left ventricular stimulation. In the other 13 patients, a clinical improvement was observed in 11 (85 per cent), that has been sustained for a mean of 8.2 months. The ejection fraction improved form 23.5 to 32.4 per cent (p < 0.001), the 6 min walking test improved from 347 to 437 m (p = 0.003) and the functional capacity changes from 3.3 to 2.7 (p < 0.001). Three patients died during follow up. One was the patient in whom the stimulation failed and two had a sudden death. No complications of the procedure were observed. CONCLUSIONS: In this series, intraventricular resynchronization with pacemakers was effective in 11 of 13 patients, improving functional capacity and ejection fraction. Sudden death could be avoided adding a defibrillator to the pacemaker system.

[SPECT tomography with F 18-fluorodeoxyglucose in a recent myocardial infarction clinical case]. / Tomografía SPECT con F18-fluorodeoxiglucosa en infarto reciente del miocardio. Caso clínico.

We report a 50-year-old woman with a recent myocardial infarction in whom a myocardial perfusion single photon emission computed tomography (SPECT) with Thallium201 was done simultaneously with a F18-fluorodeoxyglucose (FDG) SPECT to study glucose metabolism. Myocardial infarction was located in the anteroseptal and apical regions and an echocardiography, done at the second day of evolution, showed a septo-apical hypokinesia. On the tenth day, a coronary angiography showed a critical lesion of the anterior descending coronary artery and an angioplasty with stent placement was performed on the next day. On the twelfth day, a resting, redistribution 201Tl SPECT to study viability and a FDG-SPECT with a dual head high-energy collimator camera were done. Images, acquired 45 min after injection, were analyzed visually. In anterior and medial apical sectors, discordance between flux and metabolism, considered a classical mismatch, was observed. Echocardiographic hypokinesia disappeared three month after revascularization.

[Fetal echocardiography. II. Biometry of the normal fetal heart]. / Ecocardiografía fetal. II: Biometría del corazón fetal normal.

Normal fetal hearth biometry is analyzed by echocardiography in 80 pregnant women with 20 and 40 gestational weeks. Intraventricular septum, aorta, left and right ventricular dimensions were obtained. All dimensions showing progression with gestational age.

[Myocardial contraction and ventricular function in normal subjects evaluated with isotopic ventriculography and phase analysis]. / Contracción cardíaca y función ventricular en sujetos normales evaluada con ventriculografía isotópica y análisis de fase.

Normal heart contraction was studied in 20 healthy subjects (14 males and 6 female, mean age 33 years). Rest radioventriculography and phase analysis were used. Ejection fraction was 66 +/- 7% for the LV and 53 +/- 7% for the RV (p < 0.0001). Peak filling rates in the first third of diastole were 1.6 +/- 0.6 EDV/sec for the LV and 0.7 +/- 0.3 EDV/sec for RV (p < 0.0001). Time to peak filling rate normalized for heart rate was 180 +/- 52 ms for the LV and 203 +/- 60 ms for the RV (p = 0.05). Filling fractions were 23 +/- 10% and 9 +/- 3%, respectively (p < 0.0001). Segmental motility was normal in all subjects. Phase analysis revealed faster emptying of the left atrium with phase angles of 171 +/- 13 degrees in the LA and 185 +/- 12 degrees in the RA (p = 0.00007). This difference may be related to faster diastolic events in the left ventricle. Phase angles for the LV and RV were -8.75 +/- 3 and -9.44 +/- 5 degrees, respectively (NS). We conclude that activation occurs earlier in the left atrium, proceeds through the septum and then synchronically over both ventricles.

[Myocardial ischemia in patients older than 70 years of age. Clinical and angiographic aspects]. / Cardiopatía isquémica del adulto mayor de 70 años. Aspéctos clínicos y angiográficos.

We studied 77 patients with clinical suspicion of ischemic heart disease whose age ranged from 70 to 84 years. Patients with atypical angina had mostly normal coronary arteries, while those with unstable angina usually had three vessel disease or main left disease. According to the left ventricular function, surgery was considered safe in 66% of patients with unstable angina and 33% of those with stable angina. One patient developed a pseudoaneurysm at the arterial puncture site and hematomas were present in 3 other patients. Currently we try to avoid coronary arteriography in older patients with atypical angina due to its low yield.