Cutting Edge Science for Parkinson’s Clinicians 2019
Posted in Courses & Conferences on 25th Jul 2019
Conference details: 25th and 26th June 2019, Macdonald Burlington Hotel, Birmingham City Centre, UK
Report by: Anita Chadha-Patel
Conflict of interest statement: Report supplied on behalf of The Parkinson’s Academy
Published online: 25th July 2019
Cutting Edge Science for Parkinson’s Clinicians was a two-day, educational meeting sponsored by Bial Pharma UK Ltd, and delivered in association with the Parkinson’s Academy. The theme was to ‘Question everything’: reviewing what we already know, and thinking about how clinical observations and cross-team collaborations can drive us forward.
Taking a tongue in cheek approach, the Coventry & Warwickshire team reviewed how Parkinson’s treatment has changed over time. Ancient texts show that Ayurvedic, Chinese and Greek practitioners clearly understood the clinical presentations of tremor, rigidity, slowness, gait disturbance, dementia and depression as a symptom complex. They often already used plant-medicines, including levodopa-containing mucuna pruriens,1 which is still used today by patients seeking ‘alternative’ treatments. Skipping forward, the team reviewed how leading luminaries such as Charcot used astute observations to begin defining Parkinson’s for the modern day whilst Oliver Sacks, whose observations of using levodopa for post-encephalitic parkinsonism were made famous in the book ‘Awakenings’, was one of the first neurologists to warn about high doses of levodopa and the development of dyskinesia.2
The importance of multidisciplinary management in Parkinson’s is something often bandied about, yet Professor Bastiaan Bloem noted it often refers to a consultant, a nurse specialist and perhaps some physical and/or occupational therapy. Arguing that the definition of the multidisciplinary team (MDT) should reflect Parkinson’s as a multi-system disease, Prof Bloem included gastroenterologists, pulmonologists, neuro-ophthalmologists, and dentists in the adapted-to-need MDT.3 In a comprehensive review of the effectiveness of physical therapies, Professor Bloem noted well-established efficacy across various physical therapy approaches,4 and Level II evidence for occupational therapy.5
Understanding Parkinson’s as a multifactorial disease, not only affects how it should be treated, but also provides a smorgasbord of mechanisms which can be tested for their efficacy. Dr Simon Stott reviewed the current approaches to targeting disease mechanisms in Parkinson’s and advocated for a field which understands it as a syndrome. He suggested that understanding of the prodrome should help subtype the syndrome and open the door to developing tailored ‘precision’ medicine.6
Research into prodromal Parkinson’s is growing rapidly, many believing this period will be the main target for disease-modifying medications. Dr Alistair Noyce reviewed the wealth of evidence outlining constipation, REM behavioural disorder, urinary dysfunction, as well as anxiety and depression as key features of this ‘pre-diagnostic’ phase.7 Individually, they do not allow a diagnosis of Parkinson’s, but together, they reflect the gradual development of the clinical syndrome. He described the ongoing, actively recruiting, PREDICT-HD study which uses an algorithm to identify risk indicators.8
Dr Camille Carroll further considered precision medicine based on genomic subtypes, and described research into the role of homocysteine. Epidemiological evidence has clearly linked homocysteine elevation to an increased risk of coronary artery disease, stroke, and dementia. In Parkinson’s, administration of levodopa drives up homocysteine levels via the COMT pathway,9 and is associated with worse outcomes in terms of mood and cognition.10 Studies in Parkinson’s patients have shown that gene polymorphisms are related to plasma homocysteine concentration, with one genotype having much higher plasma levels than others.11 Dr Carroll discussed that while an early study showed that vitamin B supplementation, but not the COMT inhibitor entacapone, reduced homocysteine levels compared to placebo,12 the study was not enriched for the higher-risk genotypes and was too short to be able to show any impacts on cognition or mood. She proposed a revisit to the homocysteine story in light of precision medicine concepts in Parkinson’s.
Dr Alan Whone opened his presentation of the pioneering Bristol GDNF study by noting that, while the study did not meet its primary endpoint,13 it would be wrong to view it as a failure given the findings it realised. This was the first trial to use the specially developed delivery system direct to the putamen. The system was shown to be safe over 80 weeks, and is now being used in two new trials; one evaluating cerebral dopamine neurotrophic factor, and one for children with brain tumours. Dr Whone also highlighted the issue of subgroups. While the differences in clinical outcome between the GDNF and placebo groups were statistically indistinguishable, there was a relatively large variation in response. Of note, nine patients in the GDNF group, but none in the placebo group improved by more than 35%, although some did not improve at all. Understanding which patients responded best will be an important step forward.
Highlighting the neuropsychiatric symptoms (dementia, psychosis, depression, anxiety, apathy and impulse control disorders etc) in Parkinson’s, Professor Iracema Leroi argued they are so common, the disease is more accurately described as a neuropsychiatric disorder.14 Psychosis and dementia frequently co-exist, and the development of one often heralds the advent of the other.15 Together, they are associated with poorer quality of life, increased morbidity and mortality, and increased caregiver burden and nursing home placement.16 Cognitive stimulation therapy (CST) is an evidence-based psychosocial intervention that involves engaging and cognitively stimulating activities and discussions based on principles of errorless learning and validation. PD-CST is an individualised form of this treatment and can be delivered by their care partners at home.17
“Increasing age is the main non-modifiable risk for Parkinson’s. It is also the main risk factor for frailty” said Professor Richard Walker in opening. Hospital admission data shows that patients with Parkinson’s are almost twice as likely to stay in hospital for more than 3 months, and even more likely to die in hospital, than other patients.18 Admission causes include pneumonia, motor decline, urinary tract infection and hip fractures. One way to assess frailty is the frailty phenotype19 which lists five criteria: unintentional weight loss (10lb in past year), self-reported exhaustion, weakness (grip strength), slow walking speed and/or low physical activity. As Professor Walker observed, some of these are manageable, or even preventable, with good care.
- Manyam BV. Paralysis agitans and levodopa in “Ayurveda”: ancient Indian medical treatise. Mov Disord 1990;5(1):47-48.
- Santos-Lobato BL, Tumas V. Harbinger of storm: influence of Oliver Sacks on levodopa therapy in early 1970s. Arq Neuropsiquiatr 2016;74(8):687-689.
- Radder DLM, de Vries NM, Riksen NP, et al. Multidisciplinary care for people with Parkinson’s disease: the new kids on the block! Expert Rev Neurother 2019;19(2):145-157.
- Bloem BR, de Vries NM, Ebersbach G. Nonpharmacological treatments for patients with Parkinson’s disease. Mov Disord 2015;30(11):1504-1520.
- Sturkenboom IH, Graff MJ, Hendriks JC, et al. Efficacy of occupational therapy for patients with Parkinson’s disease: a randomised controlled trial. Lancet Neurol 2014;13(6):557-566.
- Titova N, Chaudhuri KR. Personalized medicine in Parkinson’s disease: Time to be precise. Mov Disord 2017;32(8):1147-1154.
- Schrag A, Horsfall L, Walters K, Noyce A, Petersen I. Prediagnostic presentations of Parkinson’s disease in primary care: a case-control study. Lancet Neurol 2015;14(1):57-64.
- Noyce AJ, R’Bibo L, Peress L, et al. PREDICT-PD: An online approach to prospectively identify risk indicators of Parkinson’s disease. Mov Disord 2017;32(2):219-226.
- Hu XW, Qin SM, Li D, Hu LF, Liu CF. Elevated homocysteine levels in levodopa-treated idiopathic Parkinson’s disease: a meta-analysis. Acta Neurol Scand 2013;128(2):73-82.
- Christine CW, Auinger P, Joslin A, Yelpaala Y, Green R, Parkinson Study Group DI. Vitamin B12 and Homocysteine Levels Predict Different Outcomes in Early Parkinson’s Disease. Mov Disord 2018;33(5):762-770.
- Yasui K, Nakaso K, Kowa H, Takeshima T, Nakashima K. Levodopa-induced hyperhomocysteinaemia in Parkinson’s disease. Acta Neurol Scand 2003;108(1):66-67.
- Postuma RB, Espay AJ, Zadikoff C, et al. Vitamins and entacapone in levodopa-induced hyperhomocysteinemia: a randomized controlled study. Neurology 2006;66(12):1941-1943.
- Whone A, Luz M, Boca M, et al. Randomized trial of intermittent intraputamenal glial cell line-derived neurotrophic factor in Parkinson’s disease. Brain 2019;142(3):512-525.
- Weintraub D, Burn DJ. Parkinson’s disease: the quintessential neuropsychiatric disorder. Mov Disord 2011;26(6):1022-1031.
- Ffytche DH, Pereira JB, Ballard C, Chaudhuri KR, Weintraub D, Aarsland D. Risk factors for early psychosis in PD: insights from the Parkinson’s Progression Markers Initiative. J Neurol Neurosurg Psychiatry 2017;88(4):325-331.
- Goldman JG, Holden S. Treatment of psychosis and dementia in Parkinson’s disease. Curr Treat Options Neurol 2014;16(3):281.
- McCormick SA, Vatter S, Carter LA, et al. Parkinson’s-adapted cognitive stimulation therapy: feasibility and acceptability in Lewy body spectrum disorders. J Neurol 2019;266(7):1756-1770.
- Low V, Ben-Shlomo Y, Coward E, Fletcher S, Walker R, Clarke CE. Measuring the burden and mortality of hospitalisation in Parkinson’s disease: A cross-sectional analysis of the English Hospital Episodes Statistics database 2009-2013. Parkinsonism Relat Disord 2015;21(5):449-454.
- Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56(3):M146-156.