Parkinson's Disease Symptoms Associated with Developing On-State Axial Symptoms Early after Subthalamic Deep Brain Stimulation.

Background: The relationship between axial symptoms in Parkinson's disease (PD) and subthalamic deep brain stimulation (STN-DBS) is still unclear. Purpose: We searched for particular clinical characteristics before STN-DBS linked to on-state axial problems after surgery. Methods: We retrospectively analyzed baseline motor, emotional and cognitive features from PD patients with early axial symptoms (within 4 years after STN-DBS) and late axial symptoms (after 4 years). We also considered a group of PD patients without axial symptoms for at least 4 years after surgery. Results: At baseline, early-axial PD patients (n = 28) had a higher on-state Unified Parkinson's Disease Rating Scale III (15.0 ± 5.6 to 11.6 ± 6.2, p = 0.020), higher axial score (2.4 ± 1.8 to 0.7 ± 1.0, p < 0.001) and worse dopaminergic response (0.62 ± 0.12 to 0.70 ± 0.11, p = 0.005), than non-axial PD patients (n = 51). Early-axial PD patients had short-term recall impairment, not seen in non-axial PD (36.3 ± 7.6 to 40.3 ± 9.3, p = 0.041). These variables were similar between late-axial PD (n = 18) and non-axial PD, but late-axial PD showed worse frontal dysfunction. Conclusions: PD patients with early axial symptoms after DBS may have a significantly worse presurgical motor phenotype, poorer dopaminergic response and memory impairment. This may correspond to a more severe form of PD.

Opicapone Improves Global Non-Motor Symptoms Burden in Parkinson's Disease: An Open-Label Prospective Study.

Patients with Parkinson's disease (PD) can improve some non-motor symptoms (NMS) after starting treatment with opicapone. The aim of this study was to analyze the effectiveness of opicapone on global NMS burden in PD. OPEN-PD (Opicapone Effectiveness on Non-motor symptoms in Parkinson's Disease) is a prospective open-label single-arm study conducted in 5 centers from Spain. The primary efficacy outcome was the change from baseline (V0) to the end of the observational period (6 months ± 30 days) (V2) in the Non-Motor Symptoms Scale (NMSS) total score. Different scales were used for analyzing the change in motor, NMS, quality of life (QoL), and disability. Thirty-three patients were included between JUL/2019 and JUN/2021 (age 63.3 ± 7.91; 60.6% males; 7.48 ± 4.22 years from symptoms onset). At 6 months, 30 patients completed the follow-up (90.9%). The NMSS total score was reduced by 27.3% (from 71.67 ± 37.12 at V0 to 52.1 ± 34.76 at V2; Cohen's effect size = −0.97; p = 0.002). By domains, improvement was observed in sleep/fatigue (−40.1%; p < 0.0001), mood/apathy (−46.6%; p = 0.001), gastrointestinal symptoms (−20.7%; p = 0.029), and miscellaneous (−44.94%; p = 0.021). QoL also improved with a 18.4% reduction in the 39-item Parkinson's Disease Quality of Life Questionnaire Summary Index (from 26.67 ± 17.61 at V0 to 21.75 ± 14.9 at V2; p = 0.001). A total of 13 adverse events in 11 patients (33.3%) were reported, 1 of which was severe (not related to opicapone). Dyskinesias and nausea were the most frequent (6.1%). Opicapone is well tolerated and improves global NMS burden and QoL in PD patients at 6 months.

Continuous subcutaneous apomorphine infusion in the early phase of advanced Parkinson's disease: A prospective study of 22 patients.

INTRODUCTION: Parkinson's disease (PD) patients usually start treatment with apomorphine infusion (APO) in later stages of advanced PD (aPD). This timing limits the evaluation of its motor efficacy and other potential clinical benefits throughout the full course of aPD. METHODS: We prospectively analyzed the effect of APO on motor and non-motor symptoms, cognitive function and quality of life (QoL) in 22 PD patients with early stage aPD, defined as: age < 71 years and diagnosis of aPD for < 3 years. RESULTS: At baseline, mean (±SD) age and disease duration were 59.4 ± 6.1 and 8.7 ± 3.5 years, respectively. After 6 months of APO treatment, daily off-time decreased from 4.98 ± 2.37 to 1.48 ± 1.47 h (p ≤ 0.001) and UPDRS IV scores from 7.00 ± 2.58 to 5.32 ± 2.48 (p = 0.018). Dyskinesia did not worsen with APO despite an overall increase in levodopa equivalent daily dose. Mean NMSS scores improved with APO, from 52.50 ± 27.24 to 38.68 ± 27.17 (p = 0.002), with particular improvements in apathy and sleep quality. Mean PDQ-39 score was reduced with APO from 31.96 ± 11.93 to 19.27 ± 11.86 (p ≤ 0.001). Overall, cognition did not change after APO, while slight improvements were observed in executive functioning (attention and planning). All but one patient eventually underwent subthalamic deep brain stimulation. CONCLUSION: In patients with early stage initial aPD, s substantial benefit of APO was observed on motor symptoms, driven by a 70% reduction in off-time versus baseline, superior to that observed in previous prospective studies. APO also improved frontal dysfunction in PD patients.

Continuous Subcutaneous Apomorphine Infusion before Subthalamic Deep Brain Stimulation: A Prospective, Comparative Study in 20 Patients.

BACKGROUND: Studies comparing the clinical efficacy of apomorphine infusion (APO) with subsequent subthalamic deep brain stimulation (STN-DBS) in advanced Parkinson's disease (aPD) are currently lacking. Retrospective data have shown that patients treated with APO are usually older, have a more prolonged disease, and a more severe phenotype. OBJECTIVE: To compare the benefit of APO with that of STN-DBS on motor, non-motor, cognitive, and quality of life in the same patient when given sequentially. METHODS: We prospectively analyzed 20 aPD patients over 3 different treatment phases: baseline (optimized medical treatment), during APO treatment, and during subsequent STN-DBS treatment. The APO and STN-DBS phases were stable for 6 months, and evaluation of the different treatments was separated by 6 months. RESULTS: Compared to baseline, APO, and STN-DBS reduced mean daily off time by 70.5% and 89.3% (P = 0.012), respectively, and scores for Unified Parkinson's Disease Rating Scale (UPDRS) IV by 27.5% and 80.5% (P ≤ 0.001), Non-motor symptoms scale (NMSS) by 24.6% and 49.3% (P ≤ 0.001), Montgomery Asberg depression scale (MADRS) by 7.4% and 39.0% (P = 0.27), Starkstein apathy scale (SAS) by 51.1% and 39.9% (P = 0.734), Parkinson's disease sleep scale 2 (PDSS-2) by 25.7% and 56.7% (P ≤ 0.001), and Parkinson's disease questionnaire 39 item (PDQ-39) by 39.6% and 64.9% (P ≤ 0.001). Global cognition did not change with either therapy, but phonetic fluency worsened after STN-DBS compared to APO (P = 0.022). CONCLUSIONS: Both APO and STN-DBS improved motor and non-motor symptoms and quality of life compared to optimized medical treatment in aPD. Overall, STN-DBS was the most effective treatment, but APO showed a pronounced benefit on motor symptoms. Effective treatment for aPD should not be delayed, even when waiting for surgery.

Polirradiculoneuropatía desmielinizante inflamatoria crónica asociada al tratamiento con infusión intraduodenal de levodopa-carbidopa / Chronic inflammatory demyelinating polyradiculoneuropathy associated with treatment using intraduodenal infusion of levodopa-carbidopa

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Continuous subcutaneous apomorphine in advanced Parkinson's disease patients treated with deep brain stimulation.

INTRODUCTION: Deep brain stimulation (DBS) is an effective therapy for patients with advanced Parkinson's disease (PD). However, sometimes, it is not sufficient to adequately control motor symptoms. We describe our experience with continuous subcutaneous apomorphine infusion (APO) in patients with DBS. METHODS: We undertook a retrospective analysis of all patients treated with DBS and APO at our centre over 12 years. Subjects were allocated to four groups: (1) APO temporarily before DBS, (2) APO after DBS complications before a new DBS, (3) APO after definitive DBS removal, and (4) APO in patients with DBS and declining response. Motor state and other parameters were analysed and compared for the different treatments. RESULTS: Data for 71 patients were evaluated. Group 1: (n = 18) patients improved their motor function significantly with both APO and DBS (off-hours before APO 5.4 ± 1.4; after APO 1.4 ± 1.2, p > 0.001; after DBS 0.7 ± 0.8, p < 0.001). Group 2: (n = 11) patients were found to have mild but significant worsening of motor state between the first DBS treatment (off-hours 0.7 ± 1.0) and APO (2.2 ± 1.5, p = 0.02), and improvement between APO and the second DBS treatment (off-hours 0.6 ± 0.8, p = 0.03). Group 3: (n = 12) patients had mild but significant worsening of motor function between DBS (off-hours 1.1 ± 1.0) and APO (2.0 ± 0.9, p = 0.03). Group 4: (n = 13) significant improvement in motor function was observed between DBS alone (off-hours 3.9 ± 2.6) and DBS combined with APO (2.2 ± 1.3, p = 0.03). CONCLUSION: In advanced PD, DBS may be not sufficient or may fail to control motor symptoms adequately. In these cases, APO, whether alone or in combination with DBS, is a good choice to improve the disease control.

Delayed complications of deep brain stimulation: 16-year experience in 249 patients.

BACKGROUND: Over the years, most of the deep brain stimulation (DBS) complications described have been mainly related to the surgery itself or the stimulation. Only a few authors have dealt with chronic complications or complications due to implanted material. METHODS: We retrospectively analyzed complications beyond the 1st month after surgery in 249 patients undergoing DBS at our site for 16 years, with 321 interventions overall. RESULTS: Our results show that infection is the most frequent delayed complication (12.5%), the pulse generator being the most common location. Lead breaks (9.3%) are the second most frequent complication. Symptomatic peri-lead edema and cyst formation were exceptional. CONCLUSIONS: The best knowledge about DBS complications allows for better solutions. In case of infection, conservative treatment or partial removal of the DBS system appears to be safe and reasonable. Intracranial complications related to DBS material such as peri-lead edema and cyst formation have a good prognosis. They may appear long after DBS implantation.

Continuous subcutaneous apomorphine infusion in advanced Parkinson's disease: 10-year experience with 230 patients.

Continuous apomorphine infusion (APO) is one of the treatments available for advanced Parkinson disease (PD). Over 10 years, we have treated 230 patients with APO. Mean age was 66.8 and average evolution time at APO onset was 13.0 years. Mean duration of the treatment was 26.3 months. As of June 2016, 93 remained on the medication (active group), while 137 had stopped. This active group had mean age 67.3 at recruitment and mean evolution 14.2 years. The main indication for APO was lack of deep brain stimulation criteria (DBS). Twelve patients were on waiting list for DBS. Average time since APO onset was 40.0 months. In the active group, APO decreased off-state in 4 h and allowed reducing levodopa and dopamine agonists. Dyskinesia and balance did not worsen. Cognitive decline did not change within the first 15 months. Hallucinations were the same within the first 39 months. The presence of subcutaneous nodules was the most frequent adverse event in this group. The main reason for discontinuation was side effects, being psychosis the most common. Within the first year, 82 patients stopped APO. Eighteen of these patients eventually got DBS. APO is a good option for advanced PD, since it permits a significant reduction in off-time and other antiparkinsonian drugs. This effect is sustained over time. We have treated 132 patients for over a year. Dyskinesia seems not to worsen. Combining APO with DBS simultaneously or alternatively provides good results.

Evaluating the Efficacy of Nocturnal Continuous Subcutaneous Apomorphine Infusion in Sleep Disorders in Advanced Parkinson's Disease: The APO-NIGHT Study.

BACKGROUND: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson's disease (PD). OBJECTIVE: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. METHODS: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. RESULTS: NCSAI allowed highly significant improvements in SCOPA-SLEEP and PDSS scales (p<0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. CONCLUSION: This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy.

Delirio de infestación asociado a deterioro cognitivo leve de etiología vascular. Buena respuesta a dosis bajas de quetiapina / Delusional parasitosis associated to mild cognitive impairment of vascular causation. Good response to low doses of quetiapine

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Ecolalia y parálisis supranuclear progresiva, una asociación inesperada / Echolalia and progressive supranuclear palsy, an unexpected association

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Recidiva después de 25 años de encefalitis por anticuerpos antirreceptor de NMDA / Recurrence of encephalitis after 25 years due to anti-NMDA receptor antibodies

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Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study.

Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in emergency visits. Wide variations in response are seen with standard antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide are approved as adjunctive therapy in the treatment of partial-onset seizures in adults and adolescents. The aim of the retrospective multicenter observational study (LACO-IV) was to analyze data from a large cohort of patients with SE or ARSs of varying severity and etiology, who received IV lacosamide in the emergency setting. Patient clinical data were entered into a database; lacosamide use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide tended to be used mainly in nonconvulsive status epilepticus as second- or third-line treatment. The proportion of patients with no seizures when IV lacosamide was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of seizure cessation ≤ 24 h after IV lacosamide administration was 57.1% (49.1% SE and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to IV lacosamide infusion influenced treatment response significantly. A nonsignificant tendency towards a higher response was seen with lacosamide dose >200mg versus ≤ 200 mg. Analysis of response according to mechanism of action showed no significant differences in response to IV lacosamide in patients receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE population; however, in ARSs, a tendency towards a higher response was observed in those receiving non-SCB AEDs. The frequency and nature of adverse events observed were in line with those reported in other studies (somnolence being the most frequent). In the absence of randomized prospective controlled studies of IV lacosamide, our observations suggest that IV lacosamide may be a potential alternative for treatment of SE/ARSs when seizures fail to improve with standard AEDs or when AEDs are contraindicated or not recommended.

Afasia y púrpura trombótica trombocitopénica en una mujer joven: el dilema del recuento plaquetario / Aphasia and thrombocytopenic thrombotic purpura in a young woman: the platelet count dilemma

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[Is necessary to perform a transthoracic echocardiogram in all the patients with cryptogenic stroke during hospitalization?]. / Es necesaria la realizacion de un ecocardiograma transtoracico a todos los pacientes con ictus isquemico indeterminado durante el ingreso?

INTRODUCTION: From 15 to 30% of all ischemic strokes are cardioembolic. Transthoracic echocardiography plays a key role in the evaluation, diagnosis and management of the embolic source. The absence of official recommendations for the use of echocardiography in patients with ischemic stroke leads to a universal application showing low diagnostic efficiency. AIM: To analyze the diagnostic accuracy of echocardiograpm in patients with ischemic stroke in two situations: with universal indication and after the application of risk clinical criteria. PATIENTS AND METHODS: Analysis of the echocardiograms performed on patients with acute ischemic stroke from the stroke unit during the years 2009-2011. We study the diagnostic and etiological contribution to the etiological study. Apply a selection criteria: 'high risk patient with need of test performance during admission' (age < 60 years, abnormal baseline electrocardiogram, cardiomegaly on chest radiograph or baseline history of heart disease, suspected endocarditis and/or active neoplasia) and analyzed their validity. RESULTS: From 930 inpatients, 201 (21.6%), underwent echocardiogram. Cardioembolic source was detected in 9.95%. After application of selection criteria, only 97 patients (10.4%) should have undergone it. The proposed criteria have a sensitivity 95%, specificity 56.9%, positive predictive value 19.6% and negative predictive value of 99%. CONCLUSIONS: The application of our criteria in undetermined stroke patients help us to identify with high efficiency cardioembolic sources postponing the test to an ambulatory scenario in the rest of the patients.

TITLE: Es necesaria la realizacion de un ecocardiograma transtoracico a todos los pacientes con ictus isquemico indeterminado durante el ingreso?Introduccion. El 15-30% de los ictus isquemicos son de origen cardioembolico. El ecocardiograma transtoracico desempena un papel fundamental en la evaluacion, diagnostico y manejo de la fuente embolica. La ausencia de recomendaciones oficiales para el empleo del ecocardiograma en pacientes con ictus isquemico lleva a una solicitud universal de la prueba, presentando una baja rentabilidad diagnostica. Objetivo. Analizar la rentabilidad diagnostica del ecocardiograma transtoracico en pacientes con ictus isquemico indeterminado tras la aplicacion de criterios clinicos predefinidos de riesgo. Pacientes y metodos. Se analizan los ecocardiogramas realizados a pacientes con ictus isquemico agudo solicitados durante 2009-2011 desde el servicio de neurologia. Se estudia la rentabilidad diagnostica y su aportacion al estudio etiologico. Se aplican unos 'criterios de seleccion de paciente de alto riego con necesidad de realizacion de la prueba durante el ingreso' (edad < 60 anos, alteraciones en el ecocardiograma basal, cardiomegalia en la radiografia de torax basal, antecedentes de cardiopatia, sospecha clinica de endocarditis o neoplasia activa) y se analiza su validez. Resultados. De 930 pacientes, se realizo ecocardiograma a 201 (21,6%) y se detecto una fuente cardioembolica en el 9,95%. Tras la aplicacion de criterios de seleccion, el numero de ecocardiogramas paso a 97 (10,4%). Los criterios propuestos presentan: sensibilidad, 95%; especificidad, 56,9%; valor predictivo positivo, 19,6%, y valor predictivo negativo, 99%. Conclusiones. La aplicacion de nuestros criterios a pacientes con ictus indeterminado identifica con alta eficiencia la fuente cardioembolica, lo que permite la realizacion del ecocardiograma transtoracico ambulatorio en el resto de los pacientes.

¿Es necesaria la realización de un ecocardiograma transtorácico a todos los pacientes con ictus isquémico indeterminado durante el ingreso? / Is necessary to perform a transthoracic echocardiogram in all the patients with cryptogenic stroke during hospitalization?

Introducción. El 15-30% de los ictus isquémicos son de origen cardioembólico. El ecocardiograma transtorácico desempeña un papel fundamental en la evaluación, diagnóstico y manejo de la fuente embólica. La ausencia de recomendaciones oficiales para el empleo del ecocardiograma en pacientes con ictus isquémico lleva a una solicitud universal de la prueba, presentando una baja rentabilidad diagnóstica. Objetivo. Analizar la rentabilidad diagnóstica del ecocardiograma transtorácico en pacientes con ictus isquémico indeterminado tras la aplicación de criterios clínicos predefinidos de riesgo. Pacientes y métodos. Se analizan los ecocardiogramas realizados a pacientes con ictus isquémico agudo solicitados durante 2009-2011 desde el servicio de neurología. Se estudia la rentabilidad diagnóstica y su aportación al estudio etiológico. Se aplican unos ‘criterios de selección de paciente de alto riego con necesidad de realización de la prueba durante el ingreso’ (edad < 60 años, alteraciones en el ecocardiograma basal, cardiomegalia en la radiografía de tórax basal, antecedentes de cardiopatía, sospecha clínica de endocarditis o neoplasia activa) y se analiza su validez. Resultados. De 930 pacientes, se realizó ecocardiograma a 201 (21,6%) y se detectó una fuente cardioembólica en el 9,95%. Tras la aplicación de criterios de selección, el número de ecocardiogramas pasó a 97 (10,4%). Los criterios propuestos presentan: sensibilidad, 95%; especificidad, 56,9%; valor predictivo positivo, 19,6%, y valor predictivo negativo, 99%. Conclusiones. La aplicación de nuestros criterios a pacientes con ictus indeterminado identifica con alta eficiencia la fuente cardioembólica, lo que permite la realización del ecocardiograma transtorácico ambulatorio en el resto de los pacientes (AU)

Introduction. From 15 to 30% of all ischemic strokes are cardioembolic. Transthoracic echocardiography plays a key role in the evaluation, diagnosis and management of the embolic source. The absence of official recommendations for the use of echocardiography in patients with ischemic stroke leads to a universal application showing low diagnostic efficiency. Aim. To analyze the diagnostic accuracy of echocardiograpm in patients with ischemic stroke in two situations: with universal indication and after the application of risk clinical criteria. Patients and methods. Analysis of the echocardiograms performed on patients with acute ischemic stroke from the stroke unit during the years 2009-2011. We study the diagnostic and etiological contribution to the etiological study. Apply a selection criteria: ‘high risk patient with need of test performance during admission’ (age < 60 years, abnormal baseline electrocardiogram, cardiomegaly on chest radiograph or baseline history of heart disease, suspected endocarditis and/or active neoplasia) and analyzed their validity Results. From 930 inpatients, 201 (21.6%), underwent echocardiogram. Cardioembolic source was detected in 9.95%. After application of selection criteria, only 97 patients (10.4%) should have undergone it. The proposed criteria have a sensitivity 95%, specificity 56.9%, positive predictive value 19.6% and negative predictive value of 99%. Conclusions. The application of our criteria in undetermined stroke patients help us to identify with high efficiency cardioembolic sources postponing the test to an ambulatory scenario in the rest of the patients (AU)