Papers by Juan Gómez-esteban
Expert Opinion on Pharmacotherapy, Jun 13, 2018
Background: PD0013 was a 6-month non-interventional study in clinical-practice comparing effectiv... more Background: PD0013 was a 6-month non-interventional study in clinical-practice comparing effectiveness and tolerability of rotigotine+levodopa in younger (<70years) vs. older (≥70years) Parkinson's disease (PD) patients. Methods: Patients previously received levodopa for ≥6-months as monotherapy or in combination with another dopamine-agonist (DA). Primary variable: Unified PD Rating Scale (UPDRS) Part-II change from baseline to end-of-observation-period (EOP). Results: 91 younger/99 older patients started rotigotine; 68 younger/62 older patients completed the study. Most switched from levodopa+another DA. Addition of rotigotine as first DA was more common in older patients (20.2% vs.15.4%). Mean±SD rotigotineexposure: 6.1±3.4mg/24h younger vs. 4.9±2.4mg/24h older. Eleven patients changed levodopa dose during the study. At EOP, improvement in mean UPDRS-II was greater in younger patients (p=0.0289). UPDRS-II responder-rate (≥20% decrease in UPDRS-II score) was higher in younger patients (42.3% vs. 25.9%). Improvement across age-groups was similar on PD Sleep Scale-2 and Clinical Global Impressions-Improvement Scale. Adverse-drug-reactions (ADRs), and discontinuations because of ADRs, were more common among older patients. There were no new safety-signals. Conclusions: Despite low rotigotine doses, when added to levodopa or switched from levodopa+another DA, rotigotine led to greater improvement in UPDRS-II in younger patients (<70years). Assessment of individual patient data revealed clinically-meaningful improvements in UPDRS-II in both age-groups.
Journal of Parkinson's disease, Feb 2, 2021
Journal of stroke and cerebrovascular diseases, Jul 1, 2018
Pain, Dec 1, 2014
A sound strategy for improving the clinical efficacy of opioids involves exploiting positive inte... more A sound strategy for improving the clinical efficacy of opioids involves exploiting positive interactions with drugs directed at other targets in pain pathways. The current study investigated the role of dopamine receptor D2 (D2R) in modulation of spinal dorsal horn excitability to noxious input, and interactions therein with μ-opioid receptor (MOR) in an animal model of neuropathic pain induced by spinal nerve ligation (SNL). C-fiber-evoked field potentials in the spinal dorsal horn were depressed concentration dependently by spinal superfusion with the D2R agonist quinpirole both in nerve-injured and sham-operated (control) rats. However, quinpirole-induced depression was significant at 10 μmol/L after SNL but only at 100 μmol/L in control rats. This quinpirole effect was completely abolished by MOR antagonist CTOP at subclinical concentration (1 μmol/L) in nerve-injured rats, but was unaltered in sham-operated rats. Nine days after SNL, D2R was upregulated to both presynaptic and postsynaptic locations in dorsal horn neurons, as revealed by double confocal immunofluorescence stainings for synaptophysin and PSD-95. In addition, D2R/MOR co-localization was increased after SNL. Co-administration of 1 μmol/L quinpirole, insufficient per se to alter evoked potentials, dramatically enhanced inhibition of evoked potentials by MOR agonist DAMGO, reducing the IC50 value of DAMGO by 2 orders of magnitude. The present data provide evidence of profound functional and subcellular changes in D2R-mediated modulation of noxious input after nerve injury, including positive interactions with spinal MOR. These results suggest D2R co-stimulation as a potential avenue to improve MOR analgesia in sustained pain states involving peripheral nerve injury.
Frontiers in Neurology, 2013
Frontiers in psychology, May 27, 2024
Introduction: Olfactory dysfunction (OD) is frequent after SARS-CoV-2 infection. The aim of this ... more Introduction: Olfactory dysfunction (OD) is frequent after SARS-CoV-2 infection. The aim of this study was to examine if long-term OD is common in post-COVID condition, and the relationship between olfaction, cognition, neuropsychiatric symptoms, and disease duration in these patients. Methods: This study included 121 participants with post-COVID condition and 51 healthy controls (HC). A comprehensive neuropsychological and neuropsychiatric assessment was conducted, encompassing various domains, including general cognition, processing speed, verbal fluency, attention, verbal memory, visual memory, visuoconstructive ability, visuospatial ability, abstraction, executive functions, anxious-depressive symptoms, general health perception, fatigue level, sleep quality, and olfaction. Statistical analyses were carried out to understand the relationship of OD with cognition, and its role as moderator variable. Results: In total, 25% of the post-covid patients had a reduced smell capacity, while only 9.3% of HC presented OD. Post-COVID patients had statistically significantly worse cognitive performance and clinical status than HC. Verbal fluency (AUC = 0.85, p < 0.001), and attention (AUC = 0.82, p < 0.001) were the variables that best discriminate between groups. OD seemed to be a moderator between fatigue and cognition, and between disease duration and attention (β = −0.04; p = 0.014). Discussion: The study highlights marked cognitive and neuropsychiatric sequelae in individuals post-COVID relative to HC. Olfactory impairment exhibits correlations with both cognitive performance and general health. Olfaction emerges as a potential prognostic marker owing to its moderating influence on disease severity indicators.
Parkinsonism & Related Disorders, Dec 1, 2016
Clinical Neurology and Neurosurgery, May 1, 2010
The presence of asymmetry in symptoms and clinical signs favours the diagnosis of Parkinson&a... more The presence of asymmetry in symptoms and clinical signs favours the diagnosis of Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease (PD). The aim of this study is to analyse this symptom asymmetry as a function of different variables and compare it with other parkinsonisms. 201 Patients with PD were studied. The sample was supplemented with 29 patients diagnosed with MSA-P (according to the criteria established by the American Academy of Neurology) and 17 with PSP (according to the criteria established by the NINDS-SPSP International Workshop). The symmetry was evaluated, based on items 20-23, 25 and 26 of the Unified Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s Disease Rating Scale, by subtracting the motor score for the left side from that for the right side. Those patients with a difference of one point or more were designated as being asymmetric. Around 16.4% of patients presented symmetrical clinical symptoms. There were no differences between those patients with or without family history of the disease. Those patients with symmetric symptoms were found to have longer symptomatic disease duration (10.8 vs. 7.9 years), a worse mental state (UPDRS I: 3.9 vs. 3.2), a higher incidence of complications (UPDRS IV: 4.5 vs. 3.2) and had their activities of daily living (ADL) affected to a greater degree (UPDRS II: 13.0 vs. 11.0). Around 48.3% of the MSA-P patients and 52.9% of the PSP patients showed symmetric symptoms. The degree of symmetry is not useful in differentiating between sporadic and familial PD. However, the observation of highly symmetrical symptoms in a patient with short evolution time indicates that an atypical parkinsonism should be suspected.
Revista De Neurologia, 2011
Gonzalez-Soltero et al [1] y Herrero-Velazquez et al [2] han presentado, recientemente, nuevos ca... more Gonzalez-Soltero et al [1] y Herrero-Velazquez et al [2] han presentado, recientemente, nuevos casos de encefalitis con anticuerpos antiNMDA-R en dos mujeres, en las que no se asocio a tumor ovarico ni en ninguna otra localizacion. El seguimiento hasta un ano despues fue negativo, sin que apareciera ninguna neoplasia ginecologica. Con este motivo queremos aportar nuestra experiencia en un caso similar, en el que el seguimiento si ha demostrado la aparicion de un teratoma de ovario. El caso ya fue publicado [3]; en resumen, se trata de una adolescente de 14 anos de edad con un cuadro agudo de trastornos del comportamiento, alucinaciones, movimientos anormales y tormenta disautonomica. En el liquido cefalorraquideo habia una ligera pleocitosis. La SPECT-HMPAO detecto focos multiples de hiperperfusion corticales y en los ganglios basales. La respuesta a la inmunoterapia fue espectacular y la paciente se recupero completamente. Fue estudiada mediante ecografia abdominopelvica, tomografia computarizada (TC) de cuerpo entero, resonancia magnetica (RM) ovarica y tomografia por emision de positrones (PET), sin detectarse ninguna tumoracion. Los marcadores tumorales fueron negativos. Tras el alta, se le realizo un seguimiento en las consultas externas de neurologia y ginecologia, sin apreciarse ninguna anomalia. Al cabo de un ano, la paciente acudio espontaneamente a urgencias por presentar molestias abdominales durante la menstruacion y haberse palpado ella misma un bulto abdominal. La TC detecto una masa de 6 cm en el ovario derecho que fue extirpada, con el diagnostico histopatologico de teratoma maduro (quiste dermoide). Hemos considerado la posibilidad de que el tumor estuviera presente en el momento del diagnostico de la encefalitis y no se detectara en las exploraciones practicadas (falso negativo). Sin embargo, se han revisado esas exploraciones iniciales de la paciente y no se ha encontrado ningun indicio de que hubiera un error de deteccion del tumor. Por la edad de la paciente, no se practico ecografia transvaginal, que se considera el metodo de eleccion para el diagnostico del teratoma ovarico, pero creemos que la combinacion de ecografia abdominal, TC, RM y PET deberia haber detectado el tumor si estuviera presente. Aportamos esta experiencia para resaltar la importancia del seguimiento prolongado de pacientes con sindromes de encefalitis antiNMDA-R, por la posibilidad de aparicion del tumor en ausencia de recidiva del sindrome neurologico.
Neurology, Apr 5, 2016
Objective: To compare the neuropsychological profile in carriers of E46K mutation of alpha-synucl... more Objective: To compare the neuropsychological profile in carriers of E46K mutation of alpha-synuclein gene (E46K-SNCA) with healthy controls (HC), idiopathic Parkinson’s disease (iPD) and dementia with Lewy bodies (DLB). Background: E46K-SNCA is a rare, highly-penetrant and clinically aggressive genetic model of pure Lewy body disease, with early and severe cognitive deficits. Methods: We evaluated cross-sectionally 63 participants including n=7 E46K-SNCA [4 symptomatic (motor parkinsonism; mean disease duration (dd): 9.1 years) and 3 asymptomatic], n=28 iPD (dd: 5.3 years), n=2 DLB (dd: 6.6 years) and n=26 HC, matched by sex, age and education. We assessed premorbid intelligence, attention, processing speed, verbal fluency, verbal and visual learning and memory, theory-of-mind (ToM), executive functioning, and higher order visual (visuospatial, visuoperceptive, visuoconstructive) skills. Mann-Whitney U Test was used to assess differences between groups. Results: Compared with HC, symptomatic E46K-SNCA showed a statistically significant lower performance in verbal fluency and verbal memory, ToM and specially processing speed and higher order visual skills. Although we did not observe significant differences between HC and asymptomatic E46K-SNCA, a tendency for poorer performance in visual memory and in both semantic and phonetic verbal fluency was found in the latter. Compared with iPD, symptomatic E46K-SNCA demonstrated significantly lower performance in processing speed, verbal fluency, learning and memory, ToM, and executive functioning. Here again, higher order visual skills were especially more affected in symptomatic E46K-SNCA. Cognitive performance was also poorer in DLB than in iPD for most cognitive domains. Interestingly, DLB cognitive profile was similar to that of symptomatic E46K-SNCA carriers, especially for verbal memory and higher order visual skills. Conclusions: Neuropsychological deterioration in E46K-SNCA is more severe and affects more cognitive domains than in iPD. Moreover, the similarities between E46K-SNCA and DLB may support the existence of a cognitive phenotype specific for alpha-synucleinopathies driven by higher order visuospatial abnormalities. Disclosure: Dr. Lucas-Jimenez has nothing to disclose. Dr. Del Pino has nothing to disclose. Dr. Acera has nothing to disclose. Dr. Gabilondo has nothing to disclose. Dr. Gomez-Esteban has nothing to disclose. Dr. Tijero has nothing to disclose. Dr. Diez-Cirarda has nothing to disclose. Dr. Pena has nothing to disclose. Dr. Ibarretxe-Bilbao has nothing to disclose. Dr. Ojeda has nothing to disclose.
Parkinsonism & Related Disorders, Jun 1, 2022
Movement Disorders Clinical Practice, Nov 1, 2018
Parkinsonism & Related Disorders, 2016
OBJECTIVE: To examine the relationship between blood pressure and symptoms in a cohort of Parkins... more OBJECTIVE: To examine the relationship between blood pressure and symptoms in a cohort of Parkinson disease (PD) patients with the goal of identifying a hemodynamic target to guide treatment. BACKGROUND: Orthostatic hypotension (OH) is frequent in patients with PD and can occur with or without symptoms. Pharmacological treatments are effective but often exacerbate supine hypertension. Guidelines exist for the diagnosis but not for the treatment of OH. METHODS: We measured blood pressure supine and upright (tilt or active standing) and identified the presence or absence of symptomatic OH by using a validated patient reported outcome questionnaire in 210 patients with PD. We evaluated the usefulness of the 20/10 and 30/15 mmHg diagnostic criteria (systolic/diastolic) to identify symptomatic OH. RESULTS: Fifty percent of the PD patient cohort met criteria for the 20/10 fall and 30[percnt] for the 30/15 blood pressure fall. Among the patients who met either OH criteria, the percentage of those with symptoms was small (33[percnt] of those with 20/10 and 44[percnt] of those with 30/15 mmHg; 16[percnt] and 13[percnt], respectively overall). Symptomatic OH was associated with an upright mean blood pressure below 75 mmHg. A mean standing blood pressure <75 mmHg had a sensitivity of 97[percnt] and a specificity of 98[percnt] for detecting symptomatic OH. CONCLUSIONS: Although the prevalence of OH in PD is high, not all patients have symptoms of organ hypoperfusion. A mean standing blood pressure below 75 mmHg appears to be a useful benchmark when deciding whether the benefits of initiating pharmacological treatment of OH outweigh the risks of exacerbating supine hypertension. Disclosure: Dr. Palma has received personal compensation for activities with Lundbeck Research USA, Inc. as a consultant. Dr. Martinez has nothing to disclose. Dr. Norcliffe-Kaufmann has nothing to disclose. Dr. Gomez-Esteban has nothing to disclose. Dr. Tijero Merino has nothing to disclose. Dr. Berganzo Corrales has nothing to disclose. Dr. Kaufmann has received personal compensation from Chelsea Therapeutics as a scientific advisory board member. Dr. Kaufmann has received personal compensation in an editorial capacity for Clinical Autonomic Research. Dr. Kaufmann has received research s
Journal of the Neurological Sciences, Oct 1, 2014
ABSTRACT •Compulsive eating was not related to dopaminergic replacement therapy.•Other impulse co... more ABSTRACT •Compulsive eating was not related to dopaminergic replacement therapy.•Other impulse control disorders showed clear relation to dopamine agonist therapy.•Punding was associated with higher dose of both dopamine agonists and L-dopa.•Rotigotine might cause less ICRBDs than other dopamine agonists.
Frontiers in Neuroscience, Jul 12, 2021
Movement Disorders, May 28, 2019
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Papers by Juan Gómez-esteban