Weeks before the US presidential election, the annual MDS congress took place in Philadelphia, in the swing state of Pennsylvania. This historical city contains the Liberty Bell, and is the home of Noam Chomsky, Solomon Burke, Samuel Barber, and the Philly Cheesesteak. Over 4800 delegates from more than 100 countries gathered for a clinical and research update. This meeting was supposed to take place in Philadelphia in 2020, but a certain pandemic got in the way.
One of the main themes was recent advances in biomarkers. Four seed amplification assay (SAA) studies were presented. Winner of the MDS Junior Award, Dr Ed Jabbari presented data on a newly developed SSA for 4-repeat tau (4-RT) [1]. Clinically distinguishing between Parkinson’s disease (PD), an alpha-synucleinopathy, and Progressive Supranuclear Palsy (PSP), a tauopathy, can be challenging. Dr Jabbari reports that by combining SAAs for alpha-synuclein and 4-RT, the two disorder can be reliably differentiated.
Another major theme was the evolving impact of artificial intelligence (AI). During the conference AI or machine learning was proposed for identification of novel biomarkers, diagnosis/disease prediction, monitoring and, in the case of adaptive deep brain stimulation surgery, treatment. At minimum, we hope that AI will allow us more time with patients. The keynote address was given by Dina Katabi, a Computer Scientist from Massachusetts Institute of Technology. In her fascinating talk, Professor Katabi explained that machine learning can be used to recognise physiological signs and diagnose neurological disorders using wireless signals. In one paper, nocturnal breathing signals were used to accurately diagnose PD [2].
The results of the EPSILON trial were announced. EPSILON is a phase III, double-blind, randomised, placebo-controlled study, designed to evaluate the efficacy and safety of Opicapone as add-on to levodopa in patients with early PD (without motor fluctuations). The trial found that the UPDRS-III scores for patients in the active group were reduced by 6.5 points in the active group at 24 months and, after a 1-year open label extension, Opicapone did not increase the development of motor fluctuations. This study is likely to result in earlier prescription of Opicapone.
The Movement Disorders Clinical Practice research article of the year was awarded to a paper that studied the role of the Levodopa challenge test in predicting the outcome of subthalamic nucleus deep brain stimulation (DBS). In this multicentre study of 429 patients, there was correlation seen in absolute UPDRS-III reduction before and after stimulation. However, this correlation did not allow the authors to predict an individual’s response, especially where the range of improvement was large. The role of the levodopa challenge in identifying the non-responders remains crucial in the assessment of DBS candidates [3].
The Grand Rounds has rapidly become a congress highlight. Respected clinicians are invited to meet brave patients, take a history, clinically examine the patients, and formulate a differential diagnosis, all in front of a packed audience of second-guessing clinicians. First up was Marie Vidaillhet (France) who correctly diagnosed myoclonus dystonia in a 35-year-old male and his 7-year-old daughter. Next, Pichet Termsarasab (Thailand) assessed a 79-year-old lady with an autosomal dominant late-onset cerebellar syndrome. He correctly diagnosed SCA 27B because of the presence of downbeat nystagmus and the audience were suitably impressed. The third case was an atypical presentation of Huntington’s disease. The fourth and final case was a 19-year-old-male who was accompanied on stage by his parents. His parents described how he had presented at 8 months with reduced muscle tone and motor delay. The discussant, Jennifer Friedman (USA) was told that there had been a dramatic response to a “treatment”, which he still takes regularly. Clinical examination found subtle perioral movements, dystonic limb posturing and myoclonic jerks. Following a detailed history, Dr Friedman correctly concluded that the patient had Tyrosine Hydroxylase deficiency, and the treatment had been Levodopa. It is always enlightening to listen to another neurologist explain their clinical process in real time, and that is why these sessions remain popular.
Dr Macías-García (Spain) presented the findings of a study combining specialist physiotherapy with cognitive behavioural therapy in patients with functional movement disorders [4]. In this parallel randomised clinical trial, patients were randomised to multidisciplinary treatment or psychological intervention alone. Multidisciplinary treatment significantly improved physical aspects of quality of life. There was no significant difference between interventions on mental health–related quality of life; at months 3 and 5 after intervention, 42% and 47% of patients in the multidisciplinary-treatment group reported improved health compared with 26% and 16% in the control group, respectively.
Results from a phase II randomised, double-blind, placebo-controlled trial suggest that Ecopipam, a selective dopamine-1 receptor antagonist, reduced both motor and phonic tics in patients aged between 6 and 18 years [5]. It had a good side profile with no tardive movement disorders reported. A phase III study is underway.
Bas Bloem (Netherlands), the TED talking, lateral thinking, unofficial rockstar of the movement disorder world encouraged us to view our patients holistically and spoke movingly about how the physical world of a person with Parkinson’s shrinks as their disease progresses. Janis Miyasaki (Canada) outlined how palliative care does not just mean end-of-life care. She also discussed the challenges of providing palliative support for neurodegenerative disorders within healthcare systems where palliative medicine is closely linked to cancer care.
In the ‘controversies’ section, the audience voted on whether AI will eventually replace clinicians in diagnosing movement disorder, and whether Dementia with Lewy Bodies and Parkinson’s disease dementia are the same disorder. In short, the consensus was: they won’t and they aren’t.
At this meeting I saw several medications that were available in the US that are not licensed in Europe. This included an inhaled form of Levodopa for ‘off’ periods, Valbenazine for tardive dyskinesia, and a longer-acting type A Botulinum toxin, Daxybotulinum. I wonder how many of these medications will make it across the ocean.
I found this to be a thought-provoking meeting and enjoyed spending time in the ‘city of brotherly love’. The 2025 MDS will take place in Honolulu next October.
References
- Vaughan DP, Fumi R, Theilmann Jensen M, Georgiades T, Wu L, Lux D, Obrocki R, Lamoureux J, Ansorge O, Allinson K, Warner TT, Jaunmuktane Z, Misbahuddin A, Leigh PN, Ghosh B, Bhatia KP, Church A, Kobylecki C, Hu M, Rowe JB, Blauwendraat C, Morris HR, Jabbari E. Evaluation of cerebrospinal fluid alpha-synuclein seed amplification assay in PSP and CBS. Mov Disord. 2024 [In press].
- Yang Y, Yuan Y, Zhang G, Wang H, Chen YC, Liu Y, Tarolli CG, Crepeau D, Bukartyk J, Junna MR, Videnovic A, Ellis TD, Lipford MC, Dorsey R, Katabi D. Artificial intelligence-enabled detection and assessment of Parkinson’s disease using nocturnal breathing signals. Nat Med. 2022 Oct;28(10):2207-2215
- Wolke R, Becktepe JS, Paschen S, Helmers AK, Kübler-Weller D, Youn J, Brinker D, Bergman H, Kühn AA, Fasano A, Deuschl G. The Role of Levodopa Challenge in Predicting the Outcome of Subthalamic Deep Brain Stimulation. Mov Disord Clin Pract. 2023 Jul 11;10(8):1181-1191.
- Macías-García D, Méndez-Del Barrio M, Canal-Rivero M, Muñoz-Delgado L, Adarmes-Gómez A, Jesús S, Ojeda-Lepe E, Carrillo-García F, Palomar FJ, Gómez-Campos FJ, Martin-Rodriguez JF, Crespo-Facorro B, Ruiz-Veguilla M, Mir P. Combined Physiotherapy and Cognitive Behavioral Therapy for Functional Movement Disorders: A Randomized Clinical Trial. JAMA Neurol. 2024 Sep 1;81(9):966-976.
- D. Gilbert, G. Karkanias, S. Atkinson, F. Munschauer, S. Wanaski, T. Cunniff. Effect of Ecopipam, a Selective Dopamine-1 Receptor Antagonist, on Tic Characteristics as Assessed by the YGTSS: Results from a Phase IIb Randomized, Double-blind, Placebo-controlled Clinical Trial in Tourette Syndrome [abstract]. Mov Disord. 2024; 39 (suppl 1).
