Icíar Avilés-Olmos

Navarre Institute of Health Research

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Thomas Foltynie

University College London

Patricia Limousin

University College London

Ludvic Zrinzo

University College London

Marwan Hariz

Umeå University

Andrew J. Lees

University College London

Zinovia Kefalopoulou

University College London

Marjan Jahanshahi

University College London

Atbin Djamshidian

Innsbruck Medical University

Juan Carlos Martínez‐Castrillo

Hospital Universitario Ramón y Cajal

Jorge Guridi

Clinica Universidad de Navarra

Cooperative Institutions

John Wiley & Sons (United States)

161

University College London

National Hospital for Neurology and Neurosurgery

University of Cambridge

Centre for Movement Disorders

Clinica Universidad de Navarra

Inserm

Hospital Universitario Ramón y Cajal

Centro de Investigación Biomédica en Red

Sobell House

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What Effects Might Exenatide have on Non-Motor Symptoms in Parkinson’s Disease: A Post Hoc Analysis

Journal of Parkinson s Disease (2018)

Dilan Athauda Kate Maclagan Natalia Budnik Luca Zampedri Steve Hibbert

Background: Exenatide is a GLP-1 receptor agonist that was recently studied for potential disease-modifying effects in a randomised, placebo-controlled clinical trial in patients with moderate stage Parkinson's disease, and showed positive effects on the motor severity of the disease which were sustained 12 weeks beyond the period of exenatide exposure.Analysis of pre-defined secondary outcomes revealed no statistically significant differences between patients treated with exenatide in total non-motor symptom burden and overall quality of life measures.Objective: The response of individual non-motor symptoms to an intervention may vary and thus this post hoc analysis was conducted to explore the possible effects of exenatide compared to placebo on individual non-motor symptoms.Results: Compared to placebo, patients treated with exenatide-once weekly had greater improvements in individual domains assessing mood/depression across all observer-rated outcome measures after 48 weeks including the "mood/apathy" domain of the NMSS, -3.3 points (95% CI -6.2, -0.4), p = 0.026; the "mood" score (Q1.3+Q1.4 of the MDS-UPDRS Part 1), -0.3 points (95%CI -0.6, -0.1), p = 0.034; and a trend in the MADRS total score, -1.7 points (95%CI -3.6, 0.2), p = 0.071.In addition, there was an improvement in the "emotional well-being" domain of the PDQ-39 of 5.7 points ((95%CI -11.3, -0.1), p = 0.047 though these improvements were not sustained 12 weeks after exenatide withdrawal.At 48 weeks these changes were of a magnitude that would be subjectively meaningful to patients and were not associated with changes in motor severity or other factors, suggesting exenatide may exert independent effects on mood dysfunction.Conclusions: These exploratory findings will contribute to the design of future trials to confirm the extent of motor and non-motor symptom effects of exenatide in larger cohorts of patients.

Apathy

Post-hoc analysis

Depression

10.3233/jpd-181329

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Citations (60)

Differences in MDS‐UPDRS Scores Based on Hoehn and Yahr Stage and Disease Duration

Movement Disorders Clinical Practice (2017)

Matěj Škorvánek Pablo Martínez‐Martín Norbert Kovács Mayela Rodríguez‐Violante Jean‐Christophe Corvol

The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS-UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD.For this cross-sectional study, demographic data and MDS-UPDRS scores were collected, including HY stage. Subscores on MDS-UPDRS Parts I through IV were analyzed using 1-way analyses of variance for each HY stage and in 5-year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states.The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0-5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS-UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5-year increments of disease duration, MDS-UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states.MDS-UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5-year increments of disease duration in the first 15 years of the disease.

10.1002/mdc3.12476

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Citations (90)

Which patients with dystonia benefit from deep brain stimulation? A metaregression of individual patient outcomes

Journal of Neurology Neurosurgery & Psychiatry (2010)

Charles W. Andrews Icíar Avilés-Olmos Marwan Hariz Thomas Foltynie

There is substantial variability in the responsiveness of dystonia patients to deep brain stimulation (DBS), presumably due to the multiple causes of dystonia. This article presents the results of an analysis of the combined published results of individual patient outcomes following DBS for all types of dystonia. From 157 papers reporting clinical outcomes of DBS for dystonia, individual quantitative data were available for 466 patients with all forms of dystonia. The subclassification of these patients included 344 with primary forms of dystonia, 10 with myoclonus dystonia, 19 with heredodegenerative dystonias and 93 who had DBS for secondary dystonia. Patients with primary forms of dystonia, myoclonus dystonia, subtypes of heredo-degenerative dystonia and tardive dystonia have a greater than 50% mean improvement in dystonia severity following DBS. Among patients with primary generalised dystonia, multiple regression analysis showed that a shorter duration of symptoms (p=0.008), a lower baseline severity score (p=0.024) and DYT1 positive status (p=0.002) were all independently associated with a significantly higher percentage improvement from surgery. Patients with other forms of heredodegenerative and secondary dystonia have variable responses, making prediction of response in future patients difficult. The degree of dystonia response that justifies DBS is a highly subjective issue. Emphasis should be placed on both safety of surgical technique and an in-depth evaluation of patients9 own perception of their life before and after DBS by using validated quality of life measures, in addition to existing use of objective severity scales.

Movement Disorders

10.1136/jnnp.2010.207993

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Citations (193)

MRI-guided STN DBS in Parkinson's disease without microelectrode recording: efficacy and safety

Journal of Neurology Neurosurgery & Psychiatry (2010)

Thomas Foltynie Ludvic Zrinzo Irene Martínez‐Torres Elina Tripoliti Erika Petersen

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a commonly employed therapeutic procedure for patients with Parkinson9s disease uncontrolled by medical therapies. This series describes the outcomes of 79 consecutive patients that underwent bilateral STN DBS at the National Hospital for Neurology and Neurosurgery between November 2002 and November 2008 using an MRI-guided surgical technique without microelectrode recording. Patients underwent immediate postoperative stereotactic MR imaging. The mean (SD) error in electrode placement was 1.3 (0.6) mm. There were no haemorrhagic complications. At a median follow-up period of 12 months, there was a mean improvement in the off-medication motor part of the Unified Parkinson9s Disease Rating Scale (UPDRS III) of 27.7 points (SD 13.8) equivalent to a mean improvement of 52% (p<0.0001). In addition, there were significant improvements in dyskinesia duration, disability and pain, with a mean reduction in on-medication dyskinesia severity (sum of dyskinesia duration, disability and pain from UPDRS IV) from 3.15 (SD 2.33) pre-operatively, to 1.56 (SD 1.92) post-operatively (p=0.0001). Quality of life improved by a mean of 5.5 points (median 7.9 points, SD 17.3) on the Parkinson9s disease Questionnaire 39 summary index. This series confirms that image-guided STN DBS without microelectrode recording can lead to substantial improvements in motor disability of well-selected PD patients with accompanying improvements in quality of life and most importantly, with very low morbidity.

Subthalamic Nucleus

Neuroradiology

10.1136/jnnp.2010.205542

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Citations (244)

Thalamic‐Caudal Zona Incerta Deep Brain Stimulation for Refractory Orthostatic Tremor: A Report of 3 Cases

Movement Disorders Clinical Practice (2016)

Dilan Athauda Dejan Georgiev Icíar Avilés-Olmos Amy Peters Brian L. Day

Abstract Orthostatic tremor ( OT ) is a rare, disabling movement disorder characterized by the development of a high‐frequency tremor of the lower limbs and feelings of unsteadiness upon standing, which compel the patient to sit down or walk. Medical therapy is often unsatisfactory. Previous reports suggest that deep brain stimulation of the ventral intermediate nucleus of the thalamus may improve clinical outcomes. The authors report 3 patients who had intractable orthostatic tremor treated with bilateral deep brain stimulation of the ventral intermediate nucleus of the thalamus‐caudal zona incerta, resulting in improved and sustained clinical improvements in symptoms, although there were no apparent changes in the underlying tremor frequency or onset.

Zona incerta

Movement Disorders

10.1002/mdc3.12345

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Citations (8)

Deep brain stimulation as a treatment for chorea-acanthocytosis

Journal of Neurology (2012)

Zinovia Kefalopoulou Ludvic Zrinzo Icíar Avilés-Olmos Kailash P. Bhatia Paul Jarman

Neuroradiology

10.1007/s00415-012-6714-0

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Citations (19)

Urinary incontinence following deep brain stimulation of the pedunculopontine nucleus

Acta Neurochirurgica (2011)

Icíar Avilés-Olmos Thomas Foltynie Jalesh N. Panicker Dorothy Cowie Patricia Limousin

Pedunculopontine nucleus

Urination

Neuroradiology

Gait Disturbance

Pedunculopontine Tegmental Nucleus

Subthalamic Nucleus

Refractory (planetary science)

10.1007/s00701-011-1155-6

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Citations (40)

Predictive factors of speech intelligibility following subthalamic nucleus stimulation in consecutive patients with Parkinson's disease

Movement Disorders (2014)

Elina Tripoliti Patricia Limousin Thomas Foltynie Joseph Candelario Icíar Avilés-Olmos

ABSTRACT Speech changes after bilateral subthalamic nucleus deep brain stimulation (STN‐DBS) can be variable, with the majority of patients experiencing speech deterioration over time. The aim of this study was to describe the perceptual characteristics of speech following chronic STN‐DBS and to analyze clinical and surgical factors that could predict speech change. Fifty‐four consecutive patients (34 men; mean age ± standard deviation (SD), 58.8 ± 6.3 years; mean ± SD disease duration, 12.5 ± 4.7 years; mean ± SD levodopa equivalent, 1556 ± 671 mg/day; mean ± SD Unified Parkinson's Disease Rating Scale motor part (UPDRS‐III) off‐medication score, 48.1 ± 17.9 [range, 20‐89]; and mean ± SD UPDRS‐III on‐medication score, 12.4 ± 7.8 [range, 2‐31]) participated in this study. They were assessed before and at 1 year after surgery using the Assessment of Intelligibility for the Dysarthric Speech, the perceptual scale from Darley et al., and the UPDRS‐III. Speech intelligibility deteriorated on average by 14.4% ( P = 0.0006) after 1 year of STN‐DBS when off‐medication and by 12.3% ( P = 0.001) when on‐medication. The effect on speech was not linked to age at surgery, unlike the effect on motor outcome. The most significant predictive factors for deterioration of speech intelligibility when patients were off‐medication/on‐stimulation were lower preoperative speech intelligibility on‐medication, longer disease duration, and medially placed left hemisphere active electrode contact. Speech change after STN‐DBS is variable and multifactorial. Consistent preoperative speech evaluation would help inform patients about the possible effects of surgery. Appropriate consideration of speech deficits might assist surgical targeting, particularly of the left electrode. © 2014 International Parkinson and Movement Disorder Society

Subthalamic Nucleus

Dysarthria

Intelligibility (philosophy)

10.1002/mds.25816

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Citations (91)

Incobotulinumtoxin A for Sialorrhea in Neurological Disorders: A Real-Life Experience

Toxins (2018)

Javier Martínez‐Poles Velina Nedkova-Hristova José Bernardo Escribano Paredes Sebastián García‐Madrona Elena Natera‐Villalba

Botulinum toxin type A is one of the most useful treatments of sialorrhea in neurological disorders. Evidence for the use of incobotulinumtoxin A (inco-A) in the treatment of sialorrhea is limited. Thirty-six patients with sialorrhea were treated with infiltrations of inco-A into both parotid glands. The severity of sialorrhea was evaluated by the Drooling Severity Scale (DSS), and the Drooling Frequency Scale (DFS). Patients’ perceptions of clinical benefit were recorded via the Patient Global Impression of Improvement (PGI-I) scale. Following treatment, there was a significant difference in both the DFS and the DSS (p < 0.001). Clinical benefits on the basis of the PGI-I were present in up to 90% of patients.

Sialorrhea

Drooling

10.3390/toxins10060217

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Citations (19)

The surgical anatomy of the pedunculopontine nucleus cannot be disputed, buried or exhumed

Acta Neurochirurgica (2012)

Icíar Avilés-Olmos Thomas Foltynie Jalesh N. Panicker Dorothy Cowie Patricia Limousin

Neuroradiology

Interventional radiology

Pedunculopontine nucleus

Pedunculopontine Tegmental Nucleus

10.1007/s00701-012-1375-4

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Citations (0)