By Dr Francesco Manfredonia, Consultant Neurologist, Royal Wolverhampton NHS Trust

Parkinson’s Advanced MasterClass 34A, November 2018

 

BACKGROUND

In this project, I am going to focus on some key points and lessons learnt during the Parkinson’s Masterclass which have led to significant changes in my practice.

I am a consultant neurologist and neurophysiologist and I obtained my CCT in Neurology in 2007. I have come across Parkinson’s disease and Parkinsonisms during my training since 2000 and when became a consultant in 2007 in my capacity of general neurologist but these clinical conditions have never been an area of special interest and I thought that my understanding of the diagnostic approach and treatment needed a refresh and an update. This is the reason I enrolled in the Parkinson’s masterclass and I am happy to have attended the course as I realized that my knowledge was slightly surpassed and outmoded. I was clinging to old concepts I needed to hear from key opinion leaders in the field new and current perspectives that led me to reflect on my practice and try and modernize my approach in light of recent acquisitions.

In the following paragraphs I have tried to summarize the main points I have learned and will treasure in my future practice and I have underlined the shift in perspective which probably I believe may reflect the historical changes of thinking about Parkinson since the time I was a neurology trainee.

By highlighting these changes, I hope this project will benefit others, like me, who are holding onto old concepts or misconceptions with regard to diagnosis and management of Parkinson’s disease.

I will mainly deal with 2 areas: Diagnosis and Symptomatic treatment since these are more relevant to my practice.

In these 2 areas, I have presented reflections that are valuable for my practice and highlighted information I gathered from the masterclass that I believe will inform my future management of this condition. I have tried to distinguish clearly my OLD approach/conception to the NEW understanding I have gained and referenced it when appropriate. In some cases, I have made an exception and thought it would be useful to mark a persistent knowledge, that is, something that has not shifted and has not changed. I have emphasized ideas that I had already and were corroborated and reinforced by the material presented at the masterclass. I thought this might be interesting too.

For ease of use I have marked OLD ideas with the capital letter O new concepts with the capital N and static concepts reinforced or refined during the course with R as for REMAIN.

 

Diagnosis

  • Clinical Diagnosis: Diagnosis rests on clinical grounds and demonstrations of cardinal motor features. At the same time it is important to exclude atypical features, to evaluate response to treatment and assess course and progression (slow-progressive – versus acute onset or static). Be aware of mimics and request neuroimaging when there are atypical features (eg. lower limb parkinsonism – vascular? Early cognitive impairment and incontinence – NPH?). R
  • Bradykinesia: not just slowness!!! N
    • Slowness of initiation of voluntary movement with progressive reduction in speed and amplitude of repetitive movements
  • Parkinsonian syndrome instead of Parkinson’s disease – more awareness of parkinsonisms
    • SIGN Guideline 2010 Clinicians should be aware of the poor specificity of a clinical diagnosis of PD in the early stages and consider this uncertainty when giving information to the patient and planning management N
    • RED FLAGS:
      • More rapid progression
      • Poor or no response to levodopa
      • Absent or atypical dyskinesia
      • Eye movement disorder
      • Early dysarthria/dysphagia
      • Corticospinal tract signs
      • Prominent autonomic involvement
    • Focus on non-motor features N – used to concentrate on motor symptoms O
      • Non-motor features can predate motor manifestations and be as disabling (e.g. REM behaviour disorders, depression)
    • Written information provided N – did not use to provide any
      • Sharing clinic letter N
      • Signpost to parkinson.org.uk website N
      • Engage help of PD nurse R
      • Provide contact R
  • More realistic approach: discuss natural history of disease N – was offering too simplistic and optimistic view – used to ignore (deliberately? To avoid patients’ breakdown?) depression, psychosis and dementia. Overall, I underestimated the severity of the disease O. I have now been awakened to the multiple dimensions of these multifaceted neurodegenerative disorders and its complications overtime. In part, I admit that I had a paternalistic and overprotective approach and was downplaying the possible consequences of this disease to shield patients from concerns and worries. I still do not understand to what extent complications of Parkinson and natural course should be discussed.

 

Treatment

Neuroprotection:

  • No evidence that MAO-B inhibitors confers neuroprotection N – they are a symptomatic treatment as any other – effect modest compared to L-Dopa – probably more tolerated
    • Previous EFNS/MDS – ES guidelines of 2013 cited the ADAGIO study, suggesting that result of this study was compatible with the concept that 1 mg/day of Rasagiline is possibly efficacious for disease modification O.
    • On these grounds I have started many patients on MAO-B inhibitors O. This has been my very first treatment option, almost a necessary step
    • I understand that evidence regarding disease modifying effect of Rasagiline was not robust and failed further scrutiny N. In particular, the delayed-start design which was employed inherently undermines the possibility of separating symptomatic drug benefits from disease-modifying effects.
  • Experimental treatments – there is nothing as yet which showing promising data for clinical application in the short term but it was interesting to see that research is focusing on non-dopaminergic actions, multimodal drugs and repurposing of existing drugs. I underestimated in my pathophysiological conception of Parkinson’s disease the role of other neurotransmitters and was surprised to learn that drugs targeting non-dopamine pathway may provide the key to neuroprotection N.
  • I have learnt that Vitamine E and co-enzyme Q10 should not be offered as neuroprotective treatment R.

Symptomatic treatment

  • My mental algorithm has been to divide patients according to age (below65/over 65) and offer dopamine-agonist in the younger group whilst reserving L-dopa for the elderly O. The rationale behind this was an excessive fear of long-term L-dopa side effect and in particular dyskinesia and motor fluctuation that I believe were linked to dose and duration of treatment with L-dopa. I believe this issue is still controversial and it is not clear to me whether this is still believed to be the case or not. However, I heard that there is sufficient reason to move away from this approach to one that is more tailored to the severity of motor symptoms and seeks to establish the optimal treatment as a trade-off of response and possible side effects. It is clear to me now that it is reasonable to offer L-Dopa to patients who are significantly and heavily troubled by motor symptoms, regardless of age and engaging the patient in a discussion around impact of symptoms and quality of life N.
  • Impulse control syndrome, excessive sleepiness and hallucinations: these are now well defined possible specific adverse events of symptomatic treatments for Parkinson’s disease and I understood that it is not enough to mention these at the onset of treatment as mere possibilities N. It is important to try and stratify patients in terms of risk and premorbid personality (history of alcohol consumption and/or smoking or a history of previous impulsive behaviors), identifying those that may be at higher risk of developing these unfavourable adverse events and in those, in particular, establish a plan and have a robust monitoring system in place, increasing awareness also in family members N. I learnt how crucial the assistance of a PD nurse can be in this process. I understand that Dopamine-agonists are more frequently associated with these adverse events as a class but that also L-Dopa and MAO-B inhibitors are not completely immune as I previously naively thought O.
  • I have also learned that when starting dopamine agonist therapy we should give people and their family members and carers not only oral but written information and record the discussion that has taken place around benefits and possible harms coming from the medications N. I realize now that it is vital to involve family members as people with impulse control disorder may conceal their symptoms. I used to think that oral information could suffice and now I signpost to the Parkinson Uk website whilst as a department we are working on local leaflets N.
  • With regards to dopaminergic (DA) therapy I have become now aware of DAWS as a severe, stereotyped cluster of physical and psychological symptoms that correlate with DA withdrawal in a dose-dependent manner, causing clinically significant distress or social/occupational dysfunction, refractory to levodopa and other Parkinson disease medications, and that cannot be accounted for by other clinical factors. I have never considered this syndrome before and now I am very conscious of it N. I am still very unsure on how to approach this and probably will seek opinion of psychiatrists or movement disorder specialists if I come across it.
  • With regard to daytime sleepiness I have now become aware that Modafinil can be an option. I have also been reminded that this symptom should be enquired about proactively as it can be a non-motor manifestation of PD and it can be related to DA therapy. I have also been reminded of the impact on driving, and the legal implication in terms of advising patients to stop driving and notify DVLA accordingly should they experience this symptom and in particular sudden onset of sleep N.
  • With regard to REM behaviour disorder I have learned to use melatonin besides clonazepam N.