Original article
Longitudinal evaluation using FP-CIT in patients with parkinsonism
Evaluación longitudinal con FP-CIT en pacientes con parkinsonismo
Read
4963
Timeswas read the article
991
Total PDF
3972
Total HTML
Share statistics
array:25 [ "pii" => "S2173580814000856" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2013.07.003" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "540" "copyright" => "Sociedad Española de Neurología" "copyrightAnyo" => "2013" "documento" => "article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Neurologia. 2014;29:327-33" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2553 "formatos" => array:3 [ "EPUB" => 46 "HTML" => 1968 "PDF" => 539 ] ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S0213485313001965" "issn" => "02134853" "doi" => "10.1016/j.nrl.2013.07.006" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "540" "copyright" => "Sociedad Española de Neurología" "documento" => "article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Neurologia. 2014;29:327-33" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 2729 "formatos" => array:3 [ "EPUB" => 56 "HTML" => 2117 "PDF" => 556 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Evaluación longitudinal con FP-CIT en pacientes con parkinsonismo" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "327" "paginaFinal" => "333" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Longitudinal evaluation using FP-CIT in patients with parkinsonism" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figura 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1284 "Ancho" => 3000 "Tamanyo" => 171497 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Estudio inicial (A) y control evolutivo (B) del paciente 2.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M.D. Martínez-Valle Torres, S.J. Ortega Lozano, M.J. Gómez Heredia, T. Amrani Raissouni, E. Ramos Moreno, P. Moya Espinosa, J.M. Jiménez-Hoyuela" "autores" => array:7 [ 0 => array:2 [ "nombre" => "M.D." "apellidos" => "Martínez-Valle Torres" ] 1 => array:2 [ "nombre" => "S.J." "apellidos" => "Ortega Lozano" ] 2 => array:2 [ "nombre" => "M.J." "apellidos" => "Gómez Heredia" ] 3 => array:2 [ "nombre" => "T." "apellidos" => "Amrani Raissouni" ] 4 => array:2 [ "nombre" => "E." "apellidos" => "Ramos Moreno" ] 5 => array:2 [ "nombre" => "P." "apellidos" => "Moya Espinosa" ] 6 => array:2 [ "nombre" => "J.M." "apellidos" => "Jiménez-Hoyuela" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173580814000856" "doi" => "10.1016/j.nrleng.2013.07.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580814000856?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485313001965?idApp=UINPBA00004N" "url" => "/02134853/0000002900000006/v1_201407160920/S0213485313001965/v1_201407160920/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2173580814000844" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2013.07.002" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "539" "copyright" => "Sociedad Española de Neurología" "documento" => "article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Neurologia. 2014;29:334-8" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2213 "formatos" => array:3 [ "EPUB" => 46 "HTML" => 1397 "PDF" => 770 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Intravenous thrombolysis with recombinant tissue plasminogen activator in vascular warning syndromes" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "334" "paginaFinal" => "338" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trombólisis intravenosa con activador tisular del plasminógeno recombinante en los síndromes de alarma vascular" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1176 "Ancho" => 1506 "Tamanyo" => 51271 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Modified Rankin Scale at 3 months of treatment (patient total is provided).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "A. González Hernández, Ó. Fabre Pi, F. Cabrera Naranjo, A.C. López Veloso" "autores" => array:4 [ 0 => array:2 [ "nombre" => "A." "apellidos" => "González Hernández" ] 1 => array:2 [ "nombre" => "Ó." "apellidos" => "Fabre Pi" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Cabrera Naranjo" ] 3 => array:2 [ "nombre" => "A.C." "apellidos" => "López Veloso" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485313001953" "doi" => "10.1016/j.nrl.2013.07.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485313001953?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580814000844?idApp=UINPBA00004N" "url" => "/21735808/0000002900000006/v1_201407240029/S2173580814000844/v1_201407240029/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2173580814000868" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2013.07.004" "estado" => "S300" "fechaPublicacion" => "2014-07-01" "aid" => "541" "copyright" => "Sociedad Española de Neurología" "documento" => "article" "crossmark" => 0 "licencia" => "http://www.elsevier.com/open-access/userlicense/1.0/" "subdocumento" => "fla" "cita" => "Neurologia. 2014;29:321-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2708 "formatos" => array:3 [ "EPUB" => 74 "HTML" => 1923 "PDF" => 711 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Headache in the elderly: a series of 262 patients" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "321" "paginaFinal" => "326" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cefaleas en la persona mayor: características de una serie de 262 pacientes" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1168 "Ancho" => 2421 "Tamanyo" => 115260 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Comparison of headache percentages between younger and older patient groups. ICHD-2 groups from 1 to 14. Apx: appendix.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Ruiz, M.I. Pedraza, C. de la Cruz, J. Barón, I. Muñoz, C. Rodríguez, M. Celorrio, P. Mulero, S. Herrero, A.L. Guerrero" "autores" => array:10 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Ruiz" ] 1 => array:2 [ "nombre" => "M.I." "apellidos" => "Pedraza" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "de la Cruz" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Barón" ] 4 => array:2 [ "nombre" => "I." "apellidos" => "Muñoz" ] 5 => array:2 [ "nombre" => "C." "apellidos" => "Rodríguez" ] 6 => array:2 [ "nombre" => "M." "apellidos" => "Celorrio" ] 7 => array:2 [ "nombre" => "P." "apellidos" => "Mulero" ] 8 => array:2 [ "nombre" => "S." "apellidos" => "Herrero" ] 9 => array:2 [ "nombre" => "A.L." "apellidos" => "Guerrero" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485313001977" "doi" => "10.1016/j.nrl.2013.07.007" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485313001977?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580814000868?idApp=UINPBA00004N" "url" => "/21735808/0000002900000006/v1_201407240029/S2173580814000868/v1_201407240029/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Longitudinal evaluation using FP-CIT in patients with parkinsonism" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "327" "paginaFinal" => "333" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "M.D. Martínez-Valle Torres, S.J. Ortega Lozano, M.J. Gómez Heredia, T. Amrani Raissouni, E. Ramos Moreno, P. Moya Espinosa, J.M. Jiménez-Hoyuela" "autores" => array:7 [ 0 => array:4 [ "nombre" => "M.D." "apellidos" => "Martínez-Valle Torres" "email" => array:1 [ 0 => "mariad.martinezvalle.sspa@juntadeandalucia.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "S.J." "apellidos" => "Ortega Lozano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "M.J." "apellidos" => "Gómez Heredia" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "T." "apellidos" => "Amrani Raissouni" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "E." "apellidos" => "Ramos Moreno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "P." "apellidos" => "Moya Espinosa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 6 => array:3 [ "nombre" => "J.M." "apellidos" => "Jiménez-Hoyuela" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario “Virgen de la Victoria”, Málaga, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Medicina Nuclear, Hospital Universitario “San Cecilio”, Granada, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Neurología, Hospital Universitario “Virgen de la Victoria”, Málaga, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación longitudinal con FP-CIT en pacientes con parkinsonismo" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 880 "Ancho" => 1800 "Tamanyo" => 201260 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Initial study (A) and monitoring study (B) from patient 6.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Dopamine transporters (DAT) are proteins in the presynaptic terminal of dopaminergic neurons which are responsible for dopamine re-uptake. DAT density measurement, by means of SPECT or PET tomographic techniques using specific ligands, provides a direct in vivo measurement of the integrity of the striatonigral pathway. Several tracers derived from tropane and cocaine analogues, such as ioflupane or 123I-FP-CIT (N-ω-fluoropropyl-2ß-carbomethoxy-3ß-[4-iodophenyl] nortropane), have been used for these measurements. This diagnostic technique allows doctors to detect Parkinson's disease (PD) even during its premotor phase, such as in cases of olfactory deficit<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> or REM sleep behaviour disorder.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> It has been determined that in cases of loss of dopaminergic neurons, DOPA decarboxylase is up-regulated<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> while DAT receptors are down-regulated.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> In theory, this situation contributes to a high level of sensitivity. Results from SWEDD patients (Scan Without Evidence of Dopaminergic Deficit), a group accounting for 10% of the patient total according to data from different clinical studies on neuroprotective drugs, will decrease the diagnostic validity of the technique. Even after taking the presence of these patients into account, the test's negative predictive value does not reach optimal values.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Annual loss of dopaminergic neurons from the nigrostriatal pathway in patients with degenerative parkinsonism (PK) has been estimated at 6% to 13%<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> compared to the 0% to 2.5% change per decade measured in age-matched healthy controls. The rate of progression is not linear and loss is more rapid during initial stages than in advanced stages. For the above reasons, it seems logical to perform a new study after a reasonable period of time in order to assess the progression of a case of degenerative PK.</p><p id="par0015" class="elsevierStylePara elsevierViewall">This study aims to analyse a group of patients with parkinsonian syndrome (PS) who underwent serial studies with FP-CIT scans. We mainly focused on those patients with an initial evaluation classified as normal (N) and a subsequent scan classified as pathological (P) (N–P sequence). By analysing each patient's clinical history and available literature, we aim to determine the most probable causes of such a pattern as a source of potential false negative results. In the same way and as a secondary aim, we also evaluated the inverse sequence (P–N).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0020" class="elsevierStylePara elsevierViewall">We retrospectively studied 92 patients (55 men and 37 women) from our hospital's movement disorders unit. We performed two serial FP-CIT scans on each patient, one at baseline and the other at a later point to investigate discrepancies between initial scan results and the patient's clinical symptoms. We also included 20 patients with a clinical diagnosis of essential tremor as control subjects after a preliminary analysis.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The final clinical diagnosis was established after a minimum follow-up of 18 months for patients in our main study group (those with contradictory scan results). All patients were in a similar stage of the disease since doctors had requested a FP-CIT scan after the initial clinical evaluation in all cases. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the breakdown of patients according to the first provisional diagnosis.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Mean time<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation elapsed between the two studies was 26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5 months. The mean age of the patients when the initial study was performed was 69.3 years (range, 36–84) with a standard deviation of 9.2 years.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Method</span><p id="par0035" class="elsevierStylePara elsevierViewall">Images were captured 3 to 4<span class="elsevierStyleHsp" style=""></span>hours after intravenous injection of 185 MBq (5<span class="elsevierStyleHsp" style=""></span>mCi) of 123I-FP-CIT. Lugol solution had previously been administered to achieve thyroid blockade. Tomographies (SPECT) with ioflupane/FP-CIT were performed with a Siemens Symbia gamma camera with a dual head and a low-energy high-resolution collimator. A circular 360° orbit around the head was used to capture images with 3° azimuth stops, capturing 60 views with a duration of 35<span class="elsevierStyleHsp" style=""></span>seconds per stop. Matrix size was 128<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>128. Tomographic reconstruction was performed using filtered back projection algorithms with no attenuation correction and applying a Hanning filter (frequency 0.7). The scanner obtained images of transaxial slices oriented on the orbitomeatal line.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Scans were studied using semi-quantitative analysis and an uptake ratio was calculated between the area with specific activity (striatal DAT binding) and the area with non-specific activity (occipital cortex) to obtain the striatal-to-occipital ratio (S/O). To this end, we drew regions of interest (ROI) on both striata (mean counts, rectangular ROI of 250 pixels) and for average uptake in the occipital lobe (rectangular ROI of 350 pixels). The 6 slices with the highest striatal activity were digitally summed (slice thickness: 3.39<span class="elsevierStyleHsp" style=""></span>mm; final slice: 20.34<span class="elsevierStyleHsp" style=""></span>mm). The arithmetic mean of the ratios of both hemispheres was calculated to provide an overall evaluation of the nigrostriatal pathway.</p><p id="par0045" class="elsevierStylePara elsevierViewall">On the basis that the distribution curve of that ratio follows a normal pattern, the study was considered normal when the index fell in the range of the mean ±2 SD of the control group. It was considered pathological when the ratio fell outside the mean −2 SD. The control group had a mean S/O ratio of 1.60 with an SD of 0.10. Therefore, every S/O ratio below 1.40 was considered a pathological finding. We established 4 study groups according to FP-CIT scan results from the initial and final studies: N–N, P–P, N–P and P–N groups/sequences. These latter 2 discordant groups or sequences constitute the main focus of our study.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The discrepancy between clinical and scan results was identified when, based on the patient's clinical presentation and subsequent outcome, the neurologist in charge found signs suggesting degenerative PK after an initial FP-CIT scan study showed results in the normal range, or when a patient whose initial study was considered pathological showed no subsequent degenerative signs. In this task, the physician considered scores on outcome scales, atypical signs, response to <span class="elsevierStyleSmallCaps">l</span>-DOPA or dopaminergic agonists, potential pharmacological interference, etc. In cases in which a possible interference was detected, we repeated the study once the patient had stopped taking the drug for a period equivalent to 4 times its biological half-life.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Data were analysed using SPSS statistical software (version 13.0). Measures of central tendency and dispersion were used to describe quantitative variables. A parametric test (<span class="elsevierStyleItalic">t</span>-test) was used to compare means. In general, the level of statistical significance was <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05 with a confidence interval of 95%. Normal distribution of the curve was established using the Kolmogorov–Smirnov test.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">A total of 184 studies were performed on 92 patients; 81 of 92 individuals (88%) showed concordant results between the initial and follow-up studies; 51 of 81 (62.9%) had normal results on both the initial and the follow-up studies (N–N). In 30 of 81 patients, results from both studies were considered pathological (P–P). Lastly, results were discordant in 11 of the 92 cases (11.9%). In this group, initial results were normal and follow-up results were pathological (N–P) in 7 of 11 cases; in the remaining 4 cases, the sequence was reversed (P–N).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The semi-quantitative assessment provided the following data: mean S/O ratio corresponding to patients with concordant results from both studies, N–N sequence, was 1.58<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.10 (initial); 1.56<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.11 (final); <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.05. P–P sequence: 1.26<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.11 (initial); 1.20<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.12 (final); <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.05. P–N sequence: 1.32<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.10; 1.48<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.12; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.05. N–P sequence: 1.50<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.12; 1.35<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.10; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>.05. Estimated mean annual loss rate in this last group was 8.15%<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.5%. The mean S/O ratio for the control group is 1.60<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.11. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows all these data. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> displays the predominant clinical sign in the N–P group as well as relevant data on the semi-quantitative assessment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">If we analyse the predominant clinical signs of patients with a normal initial study and a pathological follow-up study (N–P), using earlier studies as a reference, we learn that possible causes of these findings may be related to the tremor-dominant signs with little to no rigidity/hypokinesia that presented in 4 of 7 individuals (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). One patient in 7 presented PS, classified as stage I according to the Hoehn and Yahr (H&Y) scale. He was being treated concomitantly with an antidopaminergic drug (flupentixol) (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). Another individual was classified as a possible case of multiple system atrophy of cerebellar type (MSA-C) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>), while yet another patient presented clinical signs indicative of atypical PK but we did not find an explanation for these discrepant results.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">For patients with a P–N sequence, we confirmed that 3 out of 4 were treated with a selective serotonin reuptake inhibitor (SSRIs) at the time of the study with FP-CIT+. After one patient's treatment was suspended, we measured a significant increase in the S/O ratio (due to decreased background activity). Nevertheless, general low uptake persisted in the right striatum with no alterations in the left. After clinical follow-up, the patient was diagnosed with vascular PK (<a class="elsevierStyleCrossRef" href="#fig0025">Fig. 5</a>). One patient was being treated with bupropion as a smoking cessation aid.</p><elsevierMultimedia ident="fig0025"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0080" class="elsevierStylePara elsevierViewall">The results obtained show that in 88.04% of patients, results from initial and subsequent follow-up studies were concordant. Discordant results were found for 11 patients, including 7 cases with an N–P sequence. In the initial study, these 7 patients showed an S/O ratio within the normal range. The mean value was lower than that of the control group and clearly higher than the mean in the pathological group. This supports our first assumption that there are clinical situations that initially give rise to less functional involvement of the nigrostriatal pathway than might be expected.</p><p id="par0085" class="elsevierStylePara elsevierViewall">When we analysed their clinical histories, we observed the following data of interest. Leaving individual peculiarities aside, 4 patients presented PS with initial tremor-predominant signs and little to no rigidity/hypokinesia. Several studies have shown that there is little correlation between tremor severity and striatal uptake of FP-CIT.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,9</span></a> This has also been demonstrated when F-DOPA is used in PET techniques.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> Some authors have suggested that morphological patterns of involvement in akinetic-rigid PK differ from those in tremor-predominant forms. While akinetic-rigid PK is characterised by neuronal loss mainly in the ventrolateral part of the substantia nigra (which features projections to the putamina), the tremor-predominant type shows more restrained neuronal loss throughout the substantia nigra.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> In this context, and using FP-CIT as presynaptic marker, 2 recent studies corroborated these neuropathological models. Rossi et al.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> assess the pattern of affectation in several clinical phenotypes of initial PD. The tremor-predominant variant demonstrates better preservation of the putamen than akinetic-rigid variants; this indicates that neurotransmission systems other than the dopaminergic system are involved in tremor genesis. On the other hand, Eggers et al.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> describe a more severe loss of projection to the dorsal putamen in the akinetic-rigid types and to the lateral putamen in the tremor-dominant PD. From the clinical point of view, some observations also support the idea that the origin of tremor may differ from that of bradykinesia, based on the slow progression of tremor-dominant PD,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> bradykinesia/rigidity's better response to levodopa, and the fact that thalamotomy elicits improvements in tremor and not in other symptoms. Other authors have contemplated the possibility that tremor is not directly related to dopaminergic neuronal loss.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">One of the 7 discordant cases, a man whose main clinical signs were mixed-type tremor, cerebellar ataxia, and erectile dysfunction was diagnosed with probable MSA-C. MSA exerts variable effects on several systems (pyramidal, cerebellar, autonomic nervous, and nigrostriatal). In the case of MSA-C, the only consistent finding is cerebellar cortical degeneration. Nigral degeneration in this entity is not as obvious as in MSA-P, a condition in which parkinsonian signs predominate. A recent study performed by our group<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> shows that FP-CIT scan cannot rule out the presence of MSA-C, at least not in initial stages.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Returning to the patients with an N–P sequence, one individual previously treated with an antidopaminergic drug presented initial parkinsonian signs (H&Y score I). Occupancy of D2 receptors after this treatment might lead to signs of early onset parkinsonism if there is a subclinical dopaminergic deficit at the synaptic level, even when dopaminergic neuronal cell loss in the nigrostriatal pathways has not reached the minimum threshold to be detected by the FP-CIT scan. The review by Kägi et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> of the role of FP-CIT in movement disorders points to evidence suggesting that antidopaminergic drugs can reveal PD in patients who are still in the pre-symptomatic stage. Kim et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> followed up on 20 patients diagnosed with drug-induced PK for 2 years and studied them using DAT marker with the PET technique and MIBG scintiscan. They highlighted that the initial study with DAT marker was normal in 2 out of 20 patients, although patients showed altered myocardial sympathetic innervation. Two months after antipsychotic treatment was suspended, both patients’ parkinsonian symptoms improved, but they developed new PK symptoms after 2 years with pathological DAT scan findings.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Lastly, one patient with atypical PS and progressive bulbar involvement, rigidity, and limb apraxia also presented a normal initial study and pathological follow-up study, and we could not determine an explanation for this profile.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Regarding the patient group with P–N sequence, we should mention that treatment with SSRIs produces an increase in non-specific activity, resulting in a decrease in the uptake ratio of specific and non-specific activity (S/O ratio).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> FP-CIT does not show selective affinity for DAT receptors given that it also binds to serotonin receptors. Although blocking the serotonin receptors has no effect on striatal uptake, it results in an increase in available substrate that will augment non-specific activity due to an increase in the vascular pool. In contrast, bupropion binds to the DAT receptor and therefore directly competes with FP-CIT for binding sites, resulting in altered uptake at the striatal level.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Part of a study similar to this one also assessed dopaminergic neuron loss using sequential FP-CIT scans; it was designed on a larger scale since it was a European multicentre study, but it contained a similar number of patients.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Out of 99 patients, there were only 2 cases of discordant results between the initial study and the follow-up study at 36 months. One of the patients with an N–P sequence identified after 36 months of follow-up was listed as a possible case of PD, while the other patient with P–N sequence had a final diagnosis of probable PD. However, the study provides no potential explanations for discrepancies between initial and final results.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Another very interesting point raised by this study is the high level of inter-individual variability in the rate of disease progression. This phenomenon remains poorly understood, although it has been reported in other longitudinal studies as well as our own.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> On possible explanation could be that in pathological studies, incidence of dementia with Lewy bodies is 14 to 16 times that of PD.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> This subclinical nigrostriatal dysfunction could explain cases of individual susceptibility/variability.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Among our study's limitations, we are aware of the inaccuracies that may result from using an ROI that does not exclusively circumscribe the area of specific activity and which includes areas of non-specific activity, as in the case of the ROI for striatal structures. This fact might deliver a more or less inaccurate estimation of semi-quantitative parameters, above all when there is a marked loss of dopamine receptors. Furthermore, we should stress that knowing the results of the FP-CIT study before the final diagnosis creates a bias, but that this is difficult to avoid in retrospective studies on imaging techniques.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion, although performing serial FP-CIT studies in the context of PK is unnecessary in the vast majority of cases, they may be justified in certain clinical situations. Reviewing the clinical literature when interpreting these studies can provide relevant information.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflicts of interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres354340" "titulo" => array:5 [ 0 => "Abstract" 1 => "Objective" 2 => "Methods" 3 => "Results" 4 => "Conclusions" ] ] 1 => array:2 [ "identificador" => "xpalclavsec335688" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres354339" "titulo" => array:5 [ 0 => "Resumen" 1 => "Objetivo" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusiones" ] ] 3 => array:2 [ "identificador" => "xpalclavsec335687" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Method" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-02-27" "fechaAceptado" => "2013-07-02" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec335688" "palabras" => array:4 [ 0 => "I123-Ioflupane" 1 => "Dopamine transporters" 2 => "Parkinsonism" 3 => "False negatives" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec335687" "palabras" => array:4 [ 0 => "I123-Ioflupano" 1 => "Transportadores de dopamina" 2 => "Parkinsonismo" 3 => "Falsos negativos" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">To assess a group of patients with parkinsonism using serial studies with FP-CIT, basically the initial false negative results.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Restrospective study of 92 patients (55 men and 37 women) who had undergone 2 different FP-CIT studies because of discrepancies between study results and clinical progression. The mean elapsed time between the studies was 26 months (SD: 6). We performed a semi-quantitative study using the patient's clinical history and the available literature to analyse discrepant cases with a normal initial study and subsequent pathological findings.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A total of 184 studies were completed for 92 patients; 11 of those 92 showed discrepancies between initial and subsequent studies. Among the 11 discrepant cases, 7 showed a normal initial study and pathological findings at a later date. Analysis of the predominant clinical features that might explain this behaviour revealed that 4 of these 7 subjects presented tremor-dominant parkinsonism. Regarding the rest, 1 presented early stage parkinsonism and was treated with antidopaminergic agents; 1 was classified as probable multisystem atrophy type C, and the third showed clinical signs of atypical parkinsonism without any causes of those signs being identified.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Serial FP-CIT studies are unnecessary in the large majority of cases, but they may be justifiable in certain clinical situations.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Analizar un grupo de pacientes con síndrome parkinsoniano mediante estudios seriados con FP-CIT, valorando fundamentalmente los resultados falsamente negativos iniciales.</p> <span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo en el que se incluye a 92 pacientes (55 varones y 37 mujeres), a los que se les realizó un doble estudio con FP-CIT pues existían discrepancias entre este y la evolución clínica del paciente. El tiempo medio ± desviación estándar transcurrido entre ambos estudios fue de 26 ± 6 meses. Se realizó una valoración semicuantitativa analizando mediante la historia clínica y la bibliografía disponible los casos discrepantes con estudio inicial normal y posterior patológico.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Del total de 184 estudios realizados a 92 pacientes, 11/92 mostraron resultados discrepantes entre estudio inicial y tardío. De estos, en 7/11 el estudio inicial fue normal y el posterior patológico. Los rasgos clínicos predominantes que pudieran explicar este comportamiento mostraron que en 4/7 sujetos destacó la presentación de un cuadro parkinsoniano con predominio de la clínica tremórica; 1/7 presentó un síndrome parkinsoniano en estadio inicial en tratamiento con fármaco antidopaminérgico, 1/7 fue catalogado de probable atrofia multisistema tipo C y 1/7 presentaba un cuadro de parkinsonismo atípico, sin que encontráramos justificación para dicho comportamiento.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">La realización de estudios seriados con FP-CIT carece de fundamento en gran proporción de casos, aunque existen ciertas situaciones clínicas que pueden justificarlo.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Martínez-Valle Torres MD, Ortega Lozano SJ, Gómez Heredia MJ, Amrani Raissouni T, Ramos Moreno E, Moya Espinosa P, et al. Evaluación longitudinal con FP-CIT en pacientes con parkinsonismo. Neurología. 2014;29:327–333.</p>" ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1056 "Ancho" => 1454 "Tamanyo" => 29114 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Mean value<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD of the striatum/occipital ratio of the initial study (♦) and follow-up study (¿) in the different groups and in controls. N: normal; P: pathological.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 790 "Ancho" => 1800 "Tamanyo" => 168471 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Initial study (A) and monitoring study (B) from patient 1.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 771 "Ancho" => 1800 "Tamanyo" => 152355 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Initial study (A) and monitoring study (B) from patient 2.</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Figure 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 880 "Ancho" => 1800 "Tamanyo" => 201260 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Initial study (A) and monitoring study (B) from patient 6.</p>" ] ] 4 => array:7 [ "identificador" => "fig0025" "etiqueta" => "Figure 5" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr5.jpeg" "Alto" => 866 "Ancho" => 1800 "Tamanyo" => 207457 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Initial study with treatment with SSRIs (A) and after treatment interruption (B).</p>" ] ] 5 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% Cumulative \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parkinson's disease \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Secondary parkinsonism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">16.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">32.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Atypical parkinsonism \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">47.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PD vs ET \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">63.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parkinsonian syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab529459.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Clinical approach according to initial neurological evaluation.</p>" ] ] 6 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Patient \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Parkinsonian symptoms \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">S/O ratio in the initial study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">S/O ratio in the monitoring study \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Time between studies (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Annual loss (%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Resting tremor with minimum left rigidity, mainly brachial Mild facial masking \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Bilateral resting tremor. Treated with flupentixol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Mild tremor-predominant left parkinsonian syndrome \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Parkinsonian syndrome with bulbar involvement, rigidity, and limb apraxia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Right resting tremor. No rigidity or hypokinesia \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Cerebellar ataxia with mixed tremor. No asymmetrical onset \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">71 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RUL resting tremor with mild akinesia/rigidity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab529458.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Semi-quantitative assessment of patients with a normal/pathological sequence on serial FP-CIT studies and their predominant symptoms.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Idiopathic hyposmia as a preclinical sign of Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.M. Ponsen" 1 => "D. Stoffers" 2 => "J. Booij" 3 => "B.L. van Eck-Smit" 4 => "Wolters E. Ch" 5 => "H.W. Berendse" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ana.20160" "Revista" => array:6 [ "tituloSerie" => "Ann Neurol" "fecha" => "2004" "volumen" => "56" "paginaInicial" => "173" "paginaFinal" => "181" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15293269" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combination of “idiopathic” REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Stiasny-Kolster" 1 => "Y. Doerr" 2 => "J.C. Möller" 3 => "H. Höffken" 4 => "T.M. Behr" 5 => "W.H. Oertel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/brain/awh322" "Revista" => array:6 [ "tituloSerie" => "Brain" "fecha" => "2005" "volumen" => "128" "paginaInicial" => "126" "paginaFinal" => "137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15548552" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.S. Lee" 1 => "A. Samii" 2 => "V. Sossi" 3 => "T.J. Ruth" 4 => "M. Schulzer" 5 => "J.E. Holden" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Ann Neurol" "fecha" => "2000" "volumen" => "47" "paginaInicial" => "493" "paginaFinal" => "503" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10762161" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison between the decrease of dopamine transporter and that of <span class="elsevierStyleSmallCaps">l</span>-DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal models" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Y. Ito" 1 => "M. Fujita" 2 => "S. Shimada" 3 => "Y. Watanabe" 4 => "T. Okada" 5 => "H. Kusuoka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/(SICI)1098-2396(19990301)31:3<178::AID-SYN2>3.0.CO;2-M" "Revista" => array:6 [ "tituloSerie" => "Synapse" "fecha" => "1999" "volumen" => "31" "paginaInicial" => "178" "paginaFinal" => "185" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10029235" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Accurate differentiation of parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT SPECT imaging: the [123I]-FP-CIT study group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.S. Benamer" 1 => "J. Patterson" 2 => "D.G. Grosset" 3 => "J. Booij" 4 => "K. de Bruin" 5 => "E. van Royen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2000" "volumen" => "15" "paginaInicial" => "503" "paginaFinal" => "510" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10830416" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Neuroimaging trials of Parkinson's disease progression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Seibyl" 1 => "D. Jennings" 2 => "R. Tabamo" 3 => "K. Marek" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00415-004-1704-5" "Revista" => array:7 [ "tituloSerie" => "J Neurol" "fecha" => "2004" "volumen" => "251" "numero" => "Suppl 7" "paginaInicial" => "vII9" "paginaFinal" => "vII13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15505753" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Basic pharmacokinetic principles and their application to psychotropic drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "D.J. Greenblatt" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "J Clin Psychiatry" "fecha" => "1993" "volumen" => "54" "numero" => "Suppl." "paginaInicial" => "8" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8407859" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation of Parkinson's disease severity and duration with 123I-FP-CIT SPECT striatal uptake" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H.T. Benamer" 1 => "J. Patterson" 2 => "D.J. Wyper" 3 => "D.M. Hadley" 4 => "G.J. Macphee" 5 => "D.G. Grosset" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2000" "volumen" => "15" "paginaInicial" => "692" "paginaFinal" => "698" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10928580" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation of dopamine transporter imaging with parkinsonian motor handicap: how close is it?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "W. Pirker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.10579" "Revista" => array:7 [ "tituloSerie" => "Mov Disord" "fecha" => "2003" "volumen" => "18" "numero" => "Suppl. 7" "paginaInicial" => "S43" "paginaFinal" => "S51" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14531046" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Which clinical sign of Parkinson's disease best reflects the nigrostriatal lesion" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F.J. Vingerhoets" 1 => "M. Schulzer" 2 => "D.B. Calne" 3 => "B.J. Snow" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ana.410410111" "Revista" => array:6 [ "tituloSerie" => "Ann Neurol" "fecha" => "1997" "volumen" => "41" "paginaInicial" => "58" "paginaFinal" => "64" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9005866" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The neuropathologic basis of different clinical subgroups of Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W. Paulus" 1 => "K. Jellinger" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Neuropathol Exp Neurol" "fecha" => "1991" "volumen" => "50" "paginaInicial" => "743" "paginaFinal" => "755" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1748881" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Differences in nigro-striatal impairment in clinical variants of early Parkinson's disease: evidence from a FP-CIT SPECT study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Rossi" 1 => "D. Frosini" 2 => "D. Volterrani" 3 => "P. De Feo" 4 => "E. Unti" 5 => "V. Nicoletti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1468-1331.2009.02898.x" "Revista" => array:6 [ "tituloSerie" => "Eur J Neurol" "fecha" => "2010" "volumen" => "17" "paginaInicial" => "626" "paginaFinal" => "630" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20050904" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Akinetic-rigid and tremor-dominant Parkinson's disease patients show different patterns of FP-CIT single photon emission computed tomography" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Eggers" 1 => "D. Kahraman" 2 => "G.R. Fink" 3 => "M. Schmidt" 4 => "L. Timmermann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.23468" "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2011" "volumen" => "26" "paginaInicial" => "416" "paginaFinal" => "423" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21264942" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parkinsonism – recognition and differential diagnosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N. Quinn" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1995" "volumen" => "310" "paginaInicial" => "447" "paginaFinal" => "452" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7646647" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Measurement of the dopaminergic degeneration in Parkinson's disease with [123I] beta-CIT and SPECT. Correlation with clinical findings and comparison with multiple system atrophy and progressive supranuclear palsy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Brücke" 1 => "S. Asenbaum" 2 => "W. Pirker" 3 => "S. Djamshidian" 4 => "S. Wenger" 5 => "C. Wöber" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Neural Transm Suppl" "fecha" => "1997" "volumen" => "50" "paginaInicial" => "9" "paginaFinal" => "24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9120429" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Functional assessment of nigro-striatal pathway with FP-CIT in patients with multiple system atrophy subtype C" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.D. Martínez del Valle Torres" 1 => "E. Ramos Moreno" 2 => "T. Amrani Raissouni" 3 => "S.J. Ortega Lozano" 4 => "S. Sanz Viedma" 5 => "J.M. Jiménez-Hoyuela" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Med Clin (Barc)" "fecha" => "2011" "volumen" => "137" "paginaInicial" => "440" "paginaFinal" => "443" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of DAT-SPECT in movement disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Kägi" 1 => "K.P. Bhatia" 2 => "E. Tolosa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/jnnp.2008.157370" "Revista" => array:6 [ "tituloSerie" => "J Neurol Neurosurg Psychiatry" "fecha" => "2010" "volumen" => "81" "paginaInicial" => "5" "paginaFinal" => "12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20019219" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined use of (123)I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter (DAT) positron emission tomography (PET) predicts prognosis in drug-induced Parkinsonism (DIP): a 2-year follow-up study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S. Kim" 1 => "Y.S. Oh" 2 => "Y.I. Kim" 3 => "D.W. Yang" 4 => "Y.A. Chung" 5 => "I.R. You" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.archger.2012.05.001" "Revista" => array:6 [ "tituloSerie" => "Arch Gerontol Geriatr" "fecha" => "2013" "volumen" => "56" "paginaInicial" => "124" "paginaFinal" => "128" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22633343" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quantification of striatal dopamine transporters with 123I-FP-CIT SPECT is influenced by the selective serotonin reuptake inhibitor paroxetine: a double-blind, placebo-controlled, crossover study in healthy control subjects" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J. Booij" 1 => "J. de Jong" 2 => "K. de Bruin" 3 => "R. Knol" 4 => "M.M. de Win" 5 => "B.L. van Eck-Smit" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Nucl Med" "fecha" => "2007" "volumen" => "48" "paginaInicial" => "359" "paginaFinal" => "366" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17332612" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dopamine transporter availability in medication free and in bupropion treated depression: a 99mTc-TRODAT-1 SPECT study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Argyelán" 1 => "Z. Szabó" 2 => "B. Kanyó" 3 => "A. Tanács" 4 => "Z. Kovács" 5 => "Z. Janka" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jad.2005.08.016" "Revista" => array:6 [ "tituloSerie" => "J Affect Disord" "fecha" => "2005" "volumen" => "89" "paginaInicial" => "115" "paginaFinal" => "123" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16213028" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Parkinson's disease is overdiagnosed clinically at baseline in diagnostically uncertain cases: a 3-year European multicenter study with repeat [123I]FP-CIT SPECT" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "V.L. Marshall" 1 => "C.B. Reininger" 2 => "M. Marquardt" 3 => "J. Patterson" 4 => "D.M. Hadley" 5 => "W.H. Oertel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.22108" "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2009" "volumen" => "24" "paginaInicial" => "500" "paginaFinal" => "508" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19117369" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Measuring the rate of progression of Parkinson's disease over a 5-year period with beta-CIT SPECT" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "W. Pirker" 1 => "I. Holler" 2 => "W. Gerschlager" 3 => "S. Asenbaum" 4 => "G. Zettinig" 5 => "T. Brücke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.10531" "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2003" "volumen" => "18" "paginaInicial" => "1266" "paginaFinal" => "1272" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14639666" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Reversible drug-induced parkinsonismo. Clinicopathologic study of two cases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A.H. Rajput" 1 => "B. Rozdilsky" 2 => "O. Hornykiewicz" 3 => "K. Shannak" 4 => "T. Lee" 5 => "P. Seeman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Arch Neurol" "fecha" => "1982" "volumen" => "39" "paginaInicial" => "644" "paginaFinal" => "646" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/6127066" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735808/0000002900000006/v1_201407240029/S2173580814000856/v1_201407240029/en/main.assets" "Apartado" => array:4 [ "identificador" => "17109" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "CO1" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735808/0000002900000006/v1_201407240029/S2173580814000856/v1_201407240029/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580814000856?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 4 | 0 | 4 |
| 2024 October | 32 | 2 | 34 |
| 2024 September | 31 | 6 | 37 |
| 2024 August | 24 | 3 | 27 |
| 2024 July | 17 | 4 | 21 |
| 2024 June | 16 | 3 | 19 |
| 2024 May | 18 | 6 | 24 |
| 2024 April | 18 | 4 | 22 |
| 2024 March | 28 | 5 | 33 |
| 2024 February | 25 | 4 | 29 |
| 2024 January | 11 | 1 | 12 |
| 2023 December | 26 | 3 | 29 |
| 2023 November | 14 | 3 | 17 |
| 2023 October | 20 | 8 | 28 |
| 2023 September | 9 | 4 | 13 |
| 2023 August | 8 | 5 | 13 |
| 2023 July | 14 | 6 | 20 |
| 2023 June | 38 | 3 | 41 |
| 2023 May | 36 | 25 | 61 |
| 2023 April | 40 | 4 | 44 |
| 2023 March | 35 | 3 | 38 |
| 2023 February | 60 | 10 | 70 |
| 2023 January | 38 | 8 | 46 |
| 2022 December | 40 | 10 | 50 |
| 2022 November | 52 | 12 | 64 |
| 2022 October | 36 | 8 | 44 |
| 2022 September | 33 | 14 | 47 |
| 2022 August | 56 | 14 | 70 |
| 2022 July | 31 | 13 | 44 |
| 2022 June | 45 | 10 | 55 |
| 2022 May | 42 | 13 | 55 |
| 2022 April | 79 | 13 | 92 |
| 2022 March | 149 | 14 | 163 |
| 2022 February | 140 | 7 | 147 |
| 2022 January | 82 | 6 | 88 |
| 2021 December | 80 | 14 | 94 |
| 2021 November | 66 | 16 | 82 |
| 2021 October | 50 | 9 | 59 |
| 2021 September | 19 | 11 | 30 |
| 2021 August | 22 | 12 | 34 |
| 2021 July | 20 | 11 | 31 |
| 2021 June | 14 | 16 | 30 |
| 2021 May | 33 | 7 | 40 |
| 2021 April | 54 | 11 | 65 |
| 2021 March | 31 | 9 | 40 |
| 2021 February | 23 | 8 | 31 |
| 2021 January | 19 | 8 | 27 |
| 2020 December | 15 | 10 | 25 |
| 2020 November | 23 | 10 | 33 |
| 2020 October | 21 | 7 | 28 |
| 2020 September | 18 | 11 | 29 |
| 2020 August | 26 | 1 | 27 |
| 2020 July | 22 | 3 | 25 |
| 2020 June | 15 | 7 | 22 |
| 2020 May | 30 | 10 | 40 |
| 2020 April | 18 | 2 | 20 |
| 2020 March | 25 | 5 | 30 |
| 2020 February | 28 | 3 | 31 |
| 2020 January | 27 | 9 | 36 |
| 2019 December | 43 | 11 | 54 |
| 2019 November | 16 | 11 | 27 |
| 2019 October | 40 | 3 | 43 |
| 2019 September | 33 | 7 | 40 |
| 2019 August | 14 | 4 | 18 |
| 2019 July | 16 | 11 | 27 |
| 2019 June | 39 | 13 | 52 |
| 2019 May | 83 | 34 | 117 |
| 2019 April | 45 | 8 | 53 |
| 2019 March | 13 | 8 | 21 |
| 2019 February | 11 | 9 | 20 |
| 2019 January | 22 | 5 | 27 |
| 2018 December | 28 | 8 | 36 |
| 2018 November | 30 | 8 | 38 |
| 2018 October | 33 | 16 | 49 |
| 2018 September | 22 | 6 | 28 |
| 2018 August | 26 | 1 | 27 |
| 2018 July | 8 | 2 | 10 |
| 2018 June | 9 | 0 | 9 |
| 2018 May | 8 | 6 | 14 |
| 2018 April | 11 | 5 | 16 |
| 2018 March | 5 | 1 | 6 |
| 2018 February | 9 | 2 | 11 |
| 2018 January | 15 | 6 | 21 |
| 2017 December | 12 | 3 | 15 |
| 2017 November | 26 | 3 | 29 |
| 2017 October | 24 | 3 | 27 |
| 2017 September | 26 | 3 | 29 |
| 2017 August | 17 | 2 | 19 |
| 2017 July | 30 | 3 | 33 |
| 2017 June | 31 | 2 | 33 |
| 2017 May | 29 | 3 | 32 |
| 2017 April | 30 | 4 | 34 |
| 2017 March | 31 | 40 | 71 |
| 2017 February | 35 | 4 | 39 |
| 2017 January | 22 | 5 | 27 |
| 2016 December | 25 | 12 | 37 |
| 2016 November | 23 | 3 | 26 |
| 2016 October | 31 | 10 | 41 |
| 2016 September | 52 | 6 | 58 |
| 2016 August | 40 | 5 | 45 |
| 2016 July | 27 | 5 | 32 |
| 2016 June | 19 | 9 | 28 |
| 2016 May | 25 | 10 | 35 |
| 2016 April | 25 | 12 | 37 |
| 2016 March | 41 | 14 | 55 |
| 2016 February | 27 | 9 | 36 |
| 2016 January | 12 | 5 | 17 |
| 2015 December | 25 | 11 | 36 |
| 2015 November | 23 | 5 | 28 |
| 2015 October | 25 | 9 | 34 |
| 2015 September | 27 | 8 | 35 |
| 2015 August | 44 | 9 | 53 |
| 2015 July | 52 | 5 | 57 |
| 2015 June | 37 | 2 | 39 |
| 2015 May | 43 | 5 | 48 |
| 2015 April | 36 | 11 | 47 |
| 2015 March | 44 | 6 | 50 |
| 2015 February | 37 | 4 | 41 |
| 2015 January | 34 | 10 | 44 |
| 2014 December | 44 | 13 | 57 |
| 2014 November | 33 | 7 | 40 |
| 2014 October | 47 | 11 | 58 |
| 2014 September | 70 | 23 | 93 |
| 2014 August | 62 | 24 | 86 |
| 2014 July | 4 | 4 | 8 |
Show all
