Ischemic Stroke and Epilepsy in a Patient with Tourette´s Syndrome: Association with the Antiphospholipid Syndrome and Good Response to Levetiracetam

The role played by different humoral factors, including antiphospholipid antibodies, in the pathogenesis of Tourette syndrome (TS) is still presently unclear. We present a patient with chronic and severe TS who, at the age of 16 years, presented an ischemic stroke in the left posterior cerebral artery and/or postero-inferior temporal branch of the left medial cerebral artery. A complete study was negative with the exception of a positive lupus anticoagulant. The stroke was related with the primary antiphospholipid syndrome (APS). The stroke manifested visual abnormalities and thereafter by secondary generalized complex partial seizures. The epileptic syndrome was initially difficult to control but responded dramatically to levetiracetam. With this therapy, the manifestations of TS, especially the tics, improved. We conclude that some TS cases may present APS. In addition, levetiracetam may be useful in the management of TS. Further investigations should pursue both these facts

Improvisation in times of pandemic, a reason for reflection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been one of the most significant health crises worldwide in the last decades. This new pandemic has brought to light the strengths and weaknesses of current health care systems worldwide, even in countries that pride themselves on being at the forefront in terms of clinical, scientific, and technological capacity and development. Crises such as these are also opportunities to reflect and learn. Coronavirus disease 2019 (COVID-19) has provided us with several valuable lessons that involve the whole spectrum of medical practice: human, scientific, technical, and social

Sleep Problems Are Related to a Worse Quality of Life and a Greater Non-Motor Symptoms Burden in Parkinson’s Disease

COPPADIS Study Group.[Introduction] The aim of the present study was to examine the frequency of self-reported sleep problems and their associated factors in a large cohort of PD patients.[Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort were included in this cross-sectional study. Sleep problems were assessed by the Spanish version of the Parkinson’s disease Sleep Scale version 1 (PDSS-1). An overall score below 82 or a score below 5 on at least 1 item was defined as sleep problems.[Results] The frequency of sleep problems was nearly double in PD patients compared to controls: 65.8% (448/681) vs 33.5% (65/206) (p < 0.0001). Mean total PDSS score was lower in PD patients than controls: 114.9 ± 28.8 vs 132.8 ± 16.3 (p < 0.0001). Quality of life (QoL) was worse in PD patients with sleep problems compared to those without: PDQ-39SI, 19.3 ± 14 vs 13 ± 11.6 (p < 0.0001); EUROHIS-QoL8, 3.7 ± 0.5 vs 3.9 ± 0.5 (p < 0.0001). Non-motor symptoms burden (NMSS; OR = 1.029; 95%CI 1.015–1.043; p < 0.0001) and impulse control behaviors (QUIP-RS; OR = 1.054; 95%CI 1.009–1.101; p = 0.018) were associated with sleep problems after adjustment for age, gender, disease duration, daily equivalent levodopa dose, H&Y, UPDRS-III, UPDRS-IV, PD-CRS, BDI-II, NPI, VAS-Pain, VAFS, FOGQ, and total number of non-antiparkinsonian treatments.[Conclusion] Sleep problems were frequent in PD patients and were related to both a worse QoL and a greater non-motor symptoms burden in PD. These findings call for increased awareness of sleep problems in PD patients.Peer reviewe

Identifying comorbidities and lifestyle factors contributing to the cognitive profile of early Parkinson's disease

Background: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials. Methods: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study. Results: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005). Conclusions: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD

Predictors of Global Non-Motor Symptoms Burden Progression in Parkinson’s Disease. Results from the COPPADIS Cohort at 2-Year Follow-Up

COPPADIS Study Group.[Background and Objective] Non-motor symptoms (NMS) progress in different ways between Parkinson’s disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group.[Material and Methods] PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable).[Results] After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) (p < 0.0001). NMSS total score at baseline (β = −0.52), change from V0 to V2 in PDSS (Parkinson’s Disease Sleep Scale) (β = −0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865).[Conclusions] Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.This research was funded by Fundación Española de Ayuda a la Investigación en Parkinson y otras Enfermedades Neuro-degenerativas (Curemos el Parkinson; www.curemoselparkinson.org).Peer reviewe

Palynological and chemical volatile components of tipically autumnal honeys of the western Mediterranean

[EN] Twenty-five samples of autumnal honeys from the western Mediterranean (Mallorca and Eivissa, Balearic Islands) were examined for pollen content (qualitative and quantitative melissopalynological analysis), moisture, electrical conductivity, colour, sensorial qualities and volatile components. Quantitative analysis showed that the honey contained Maurizio's Class II: 64%, Class III: 28%, Class IV: 4% and Class V: 4%. Fifty-four pollen types, with an average number of 16.68 per sample, were identified, belonging to 29 botanical families. Only two taxa (Ceratonia siliqua and Erica multiflora) were found in all samples. Seventeen samples were unifloral (68%) - ten (40%) of C. siliqua, six (24%) of E. multiflora and one (4%) of Hedera helix. All honeys have a low honeydew index (<?0.09%), while the values for electrical conductivity and water content were high. The major honey volatile components are: cis- and trans-linalool oxides (64.2%) and hotrienol (10.4%) for the carob (C. siliqua) and trans-linalool oxide (13.4%), p-menthane-1,8-diol (11.1%), safranal (9.7%), limonene (5,4%), -pinene (3.7%) and oxoisophorone (3.4%) for the winter heather (E. multiflora).The authors would like to extend their gratitude to the Mallorca Rural 'Leader plus' programme and the beekeepers of Mallorca and Eivissa for their support and friendly collaboration. The authors also thank an anonymous reviewer for useful comments and suggestions on an earlier version of the manuscript.Boi, M.; Llorens Molina, JA.; Cortés, L.; Lladó, G.; Llorens, L. (2013). Palynological and chemical volatile components of tipically autumnal honeys of the western Mediterranean. Grana. 52(2):93-105. doi:10.1080/00173134.2012.744774S93105522Andrade, P. B., Amaral, M. T., Isabel, P., Carvalho, J. C. M. F., Seabra, R. M., & Proença da Cunha, A. (1999). 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Journal of Chromatography A, 1216(9), 1458-1462. doi:10.1016/j.chroma.2008.12.066Castro-Vázquez, L., Díaz-Maroto, M. C., González-Viñas, M. A., & Pérez-Coello, M. S. (2009). Differentiation of monofloral citrus, rosemary, eucalyptus, lavender, thyme and heather honeys based on volatile composition and sensory descriptive analysis. Food Chemistry, 112(4), 1022-1030. doi:10.1016/j.foodchem.2008.06.036Conti, M. E., Stripeikis, J., Campanella, L., Cucina, D., & Tudino, M. B. (2007). Characterization of Italian honeys (Marche Region) on the basis of their mineral content and some typical quality parameters. Chemistry Central Journal, 1(1). doi:10.1186/1752-153x-1-14Custódio, L., Serra, H., Nogueira, J. M. F., Gonçalves, S., & Romano, A. (2006). Analysis of the Volatiles Emitted by Whole Flowers and Isolated Flower Organs of the Carob Tree Using HS-SPME-GC/MS. Journal of Chemical Ecology, 32(5), 929-942. doi:10.1007/s10886-006-9044-9Cuevas-Glory, L., Ortiz-Vázquez, E., Pino, J. 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Bee World, 59(4), 139-157. doi:10.1080/0005772x.1978.11097714Martins, R. C., Lopes, V. V., Valentão, P., Carvalho, J. C. M. F., Isabel, P., Amaral, M. T., … Silva, B. M. (2008). Relevant principal component analysis applied to the characterisation of Portuguese heather honey. Natural Product Research, 22(17), 1560-1582. doi:10.1080/14786410701825004Melliou, E., & Chinou, I. (2011). Chemical constituents of selected unifloral Greek bee-honeys with antimicrobial activity. Food Chemistry, 129(2), 284-290. doi:10.1016/j.foodchem.2011.04.047Pendleton, M. (2006). Descriptions of melissopalynological methods involving centrifugation should include data for calculating Relative Centrifugal Force (RCF) or should express data in units of RCF or gravities (g). Grana, 45(1), 71-72. doi:10.1080/00173130500520479Pérez, R. A., Sánchez-Brunete, C., Calvo, R. M., & Tadeo, J. L. (2002). Analysis of Volatiles from Spanish Honeys by Solid-Phase Microextraction and Gas Chromatography−Mass Spectrometry. Journal of Agricultural and Food Chemistry, 50(9), 2633-2637. doi:10.1021/jf011551rPersano Oddo, L., Piana, L., Bogdanov, S., Bentabol, A., Gotsiou, P., Kerkvliet, J., … von der Ohe, K. (2004). Botanical species giving unifloral honey in Europe. Apidologie, 35(Suppl. 1), S82-S93. doi:10.1051/apido:2004045Persano Oddo, L., & Piro, R. (2004). Main European unifloral honeys: descriptive sheets. Apidologie, 35(Suppl. 1), S38-S81. doi:10.1051/apido:2004049Piana, M. L., Persano Oddo, L., Bentabol, A., Bruneau, E., Bogdanov, S., & Guyot Declerck, C. (2004). Sensory analysis applied to honey: state of the art. Apidologie, 35(Suppl. 1), S26-S37. doi:10.1051/apido:2004048Piasenzotto, L., Gracco, L., & Conte, L. (2003). Solid phase microextraction (SPME) applied to honey quality control. Journal of the Science of Food and Agriculture, 83(10), 1037-1044. doi:10.1002/jsfa.1502Radovic, B. S., Careri, M., Mangia, A., Musci, M., Gerboles, M., & Anklam, E. (2001). Contribution of dynamic headspace GC–MS analysis of aroma compounds to authenticity testing of honey. Food Chemistry, 72(4), 511-520. doi:10.1016/s0308-8146(00)00263-6RAMÓN-LACA, L., & MABBERLEY, D. J. (2004). The ecological status of the carob-tree (Ceratonia siliqua, Leguminosae) in the Mediterranean. Botanical Journal of the Linnean Society, 144(4), 431-436. doi:10.1111/j.1095-8339.2003.00254.xRetana, J., Ramoneda, J., Garcia Del Pino, F., & Bosch, J. (1994). Flowering phenology of carob,Ceratonia siliquaL. (Cesalpinaceae). Journal of Horticultural Science, 69(1), 97-103. doi:10.1080/14620316.1994.11515254Ricciardelli d’Albore, G. & Vorwohl, G. (1979). Mieles monoflorales en el Mediterráneo documentado con ayuda del análisis microscópico de mieles. Actas de XXVII Congreso Internacional de Apicultura, Athens, Greece, 14–20 September 1979, 201–208.Pilar de Sá‐Otero, M., Armesto‐Baztan, S., & DÍaz‐Losada, E. (2006). A study of variation in the pollen spectra of honeys sampled from the Baixa Limia‐Serra do Xurés Nature Reserve in north‐west Spain. Grana, 45(2), 137-145. doi:10.1080/00173130600708537Seijo, M. C., Jato, M. V., Aira, M. J., & Iglesias, I. (1997). Unifloral honeys of Galicia (north-west Spain). Journal of Apicultural Research, 36(3-4), 133-140. doi:10.1080/00218839.1997.11100939Terrab, A., Diez, M. J., & Heredia, F. J. (2003). Palynological, physico-chemical and colour characterization of Moroccan honeys: III. Other unifloral honey types. International Journal of Food Science and Technology, 38(4), 395-402. doi:10.1046/j.1365-2621.2003.00713.xTERRAB, A., PONTES, A., HEREDIA, F. J., & DÍEZ, M. J. (2004). A preliminary palynological characterization of Spanish thyme honeys. Botanical Journal of the Linnean Society, 146(3), 323-330. doi:10.1111/j.1095-8339.2004.00335.xTerrab, A., Valdés, B., & Josefa Díez, M. (2003). Pollen analysis of honeys from the Mamora forest region (NW Morocco). 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Predictors of clinically significant quality of life impairment in Parkinson’s disease

COPPADIS Study Group.Quality of life (QOL) plays an important role in independent living in Parkinson’s disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson’s disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829–0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422–12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053–1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027–1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer–Lemeshow test, p = 0.665; R 2 = 0.655). An increase in ≥5 and ≥10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663–17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975–22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients.Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña.Peer reviewe

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

COPPADIS Study Group.[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 (). 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 (; e.g., PDQ-39SI in 1D [n = 15] vs 2A [n = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; ).[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.Peer reviewe

Predictors of Loss of Functional Independence in Parkinson’s Disease: Results from the COPPADIS Cohort at 2-Year Follow-Up and Comparison with a Control Group

COPPADIS Study Group.[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.Fundación Curemos el Parkinson (www.curemoselparkinson.org).Peer reviewe