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Non-motor features extremely important in Parkinson’s disease – Walsh
In a debate on Parkinson’s disease at the Irish Neurological Association (INA) Annual Meeting, Consultant Neurologist in Tallaght Hospital, Dublin, Dr Richard Walsh, argued that it is a syndrome defined by synuclein pathology with prominent motor features.
While Dr Walsh said that motor features dominate discussions due to symptomatic treatment, he said non-motor symptoms dominate patients’ lives and offer the greatest potential to study possible neuroprotective agents.
“There are few examples of disorders in which we are anchored to historical clinical descriptions to define a disease,” Dr Walsh told the meeting, which was held in Dublin last month.
“In multiple sclerosis, we are moving towards an era where radiological changes are as, or more important, than clinical features. We are progressively moving away from giving patients a diagnosis of ‘ataxia’, increasingly providing a diagnosis based on the genetic underpinning of the ataxic symptom as part of syndromes with cerebellar predominance. Simplistic clinical diagnosis of delirium, psychosis and primary seizure disorders are questionable in light of huge advances in neuroimmunology.”
Dr Walsh said there had been significant evolution of understanding of Parkinson’s disease (PD) since James Parkinson’s description of the condition 200 years ago.
He argued that PD, itself a vastly heterogeneous syndrome, is one facet of a complex disorder, with more non-motor than movement-related syndromes; a long pre-motor prodrome of up to 20 years; and prominent cognitive features that often account for much of the disability in advanced disease.
“Cognitive impairment is inherent to PD and may predate motor symptoms in a large subsets of patients,” said Dr Walsh.
“Cognitive dysfunction contributes significantly to disability in late-stage PD — perhaps more than motor dysfunction. In mid-to-late stage disease, PD is a form of dementia with prominent motor features.”
He said that a greater emphasis on non-motor symptoms will allow for a recognition of at-risk pre-clinical and prodromal cohorts to enrol into neuroprotective trials and more comprehensive end-points to evaluate symptomatic therapies.
In contrast, Consultant Neurologist Dr Timothy Counihan argued that the disease should be defined chiefly by the presence of motor symptoms.
Dr Timothy Counihan
In another part of the debate, Dr Walsh said that deep-brain stimulation (DBS) should be considered as an intervention early in PD.
He said that the current application of DBS, which favours treatment at a later stage of the disease, results in a large subset of the population who are young and operating at 60-to-70 per cent of normal function throughout the day; are commonly affected by impulse control disorders; struggle to maintain a place in the workforce; and are gradually developing the sort of cognitive impairment that will exclude them from DBS.
Positive developments for secondary progressive MS
Progress is being made in developing treatment for primary and secondary progressive multiple sclerosis (MS), according to a leading neurologist.
Speaking on a ‘hot topic’ in MS, Dr Christopher McGuigan, Consultant Neurologist at St Vincent’s University Hospital, Dublin, said there was finally hope for patients with progressive illness who had traditionally proved difficult to treat.
“If we were giving this hot topic in 1997, 20 years ago, the hot topic would have been the emergence of interferon and the emergence of the first disease-modifying treatment for relapsing-remitting MS,” according to Dr McGuigan.
Dr Christopher McGuigan
“The field of MS has changed in the last 20 years. The number of treatments, the escalation of treatments and the escalation of those treatments are now clearly having in the disease modification in the relapsing-remitting types of MS, I think you will agree, has been an astonishing change. But progressive MS has always lagged behind. There have been numerous failed trials. There has always been this looming disappointment that we can do very little to impact on the course of progressive MS. Of course, I am not talking about the physical treatments, such as physiotherapy — I am purely talking here about disease modification.”
Dr McGuigan spoke about ocrelizumab, which is a humanised monoclonal antibody that selectively depletes CD20 B cells. It has been licensed in the US and is currently awaiting licensing by the European Medicines Agency for patients with primary progressive disease.
Positive results were achieved in the recent phase III ORATORIO trial, which found there was a 24 per cent relative risk reduction for confirmed disability reduction in the active treatment group compared to the placebo-controlled group.
“I think there is some argument as to what you are treating here — are you treating an unseen inflammatory component, are you treating a neurodegenerative component, and I think the answer is, we don’t fully understand,” stated Dr McGuigan.
“We know the role of B cells is becoming much more important in the pathology; it has always been important in the pathology in MS, but we are starting to understand it a little more.”
He also said results of the phase III EXPAND study for siponimod, which is a selective SIP1 and SIP5 receptor modulator, were positive for patients with secondary progressive MS.
At the three-month end-point, there was a relative risk reduction of 21 per cent vs placebo in the treated arm, and at the six-month point there was a 26 per cent relative risk reduction.
“There is a clear benefit,” noted Dr McGuigan.
“You can argue about the magnitude of change in these studies and you can argue about the impact clinically, but it reminds me about the arguments we were having 20 years ago about interferon, and I think it is very positive now that we are starting to see these medications impacting on progressive disease and behind these drugs there are a number of other drugs at phase II and earlier studies targeting the progressive phase of MS.”
Treating functional neurological disorder
Patients with functional neurological disorder (FND) should be treated as “normally” as other patients, according to a leading neurologist from the UK.
Professor of Neurology at St George’s Hospital in London, Prof Mark Edwards, delivered the Callahan Guest Lecture at the Irish Neurological Association (INA) Annual Meeting, titled ‘Functional neurological disorder: The art of being normal’.
Functional neurological disorders (FNDs) is the name given for symptoms in the body that appear to be caused by problems in the nervous system, but which are not caused by a physical neurological disease or disorder.
The neurologist’s role in patients with functional disorders has traditionally been limited to making the diagnosis, excluding a ‘disease’ and pronouncing the symptoms to be ‘non-organic’ or ‘psychogenic’.
Prof Edwards urged delegates to “just be normal” in the diagnosis and management of these patients.
“Patients expect, need and deserve assessment and diagnostic explanation from a neurologist,” stated Prof Edwards.
“A shared, coherent and individualised diagnostic explanation is the foundation of any successful treatment. Patients are heterogeneous so invest in triage into specific, relevant treatment. This needs a specific and flexible multidisciplinary rehabilitation team.”
During his talk, Prof Edwards referred to the Cognitive Behavioural Therapy for Dissociative (Non-Epileptic) Seizures (CODES) randomised, controlled trial.
The trial is assessing whether cognitive behavioural therapy helps in the treatment of patients with dissociative seizures.
Prof Edwards also referred to experimental treatments such as biofeedback and therapeutic sedation for these patients.
Throughout his talk, he stressed the importance of treating these patients with empathy and offering them a structured treatment approach.
INA President Dr Janice Redmond told the Medical Independent of the great response the talk received from delegates.
“Functional neurological problems are extremely common,” Dr Redmond said.
“You are dealing with, in a refractory epilepsy clinic, possibly 30-to-40 per cent of patients [who] don’t have epilepsy. We are all seeing functional problems all of the time and as you can see, the questions and answers could have gone on for ages.”
Prof Edwards also had a special session where he discussed specific case presentations with trainees.
Another keynote address was delivered by Consultant Neurologist in the Mater Misericordiae University Hospital, Dublin, Dr Donal Costigan, who provided reflections on his career in neurology in Canada, the US and Ireland.
His talk was titled ‘Four decades of neurology: Landmarks, pitfalls and tricks of the trade’.
Fruitful interaction at INA meeting – President
INA President Dr Janice Redmond has said the 53rd Annual Meeting of the Association has been very “encouraging” for the future of neurology on the island of Ireland.
Dr Redmond told the Medical Independent that the meeting was extremely well-attended.
“There have been a very large number of registrants from all over the country and we have been very happy with that,” according to Dr Redmond.
Dr Janice Redmond
“I think the level of audience interaction has been very high. There have been a number of new initiatives with the meeting on this occasion: We have had a clinical pathological session, which is absolutely outstanding with the involvement of our trainees. That has been an addition to a whole set of scientific presentations from house staff and trainees. There have been hot topics on every area that we have had as platform sessions that were delivered by local consultants and they have been very helpful.”
Dr Redmond also said the conference provided a useful networking opportunity for doctors working in the field.
“There has been a great interactional buzz and the networking that has taken place is very encouraging for the future of neurology in the country,” she said.
“And I think the interaction between Cork, Galway, Belfast and the development of networks in the future going forward in terms of research has been very positive.”
Dr Redmond spoke positively about the new model of care for neurological services, which was launched in September 2016.
“It has given us a blueprint for expansion,” she said. “It proposes 64 neurologists should be put in place over the next decade; that will at least be doubling our numbers. It is also not just neurologists, but also the ancillary services going with it, in terms of physiotherapists, rehabilitative occupational therapy, nurses, psychologists, and so on, so it is not just appointing people in a vacuum. I think it is a very important document and we completely endorse it.”