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Professionals' Q&A: Management of the stages of Parkinson's

Dr Nin BajajDr Nin Bajaj joined us in May 2011 to answer questions from healthcare professionals on the stages of Parkinson's and implications for professionals working with people with the condition.

Nin is clinical director of the National Parkinson Foundation Centre of Excellence in Derby.

The answers below are Nin's professional opinion.

Question categories:

Diagnosis stage

Aurora, occupational therapist: Many of my patients develop stiff and painful shoulders very early on in the condition. What causes this and what should I do to help regain/maintain function?

Nin: Frozen shoulder appears to be a common early feature in Parkinson's and often results in Parkinson's patients being referred first to orthopaedic surgeons. Often maximising the dopaminergic control is the key to ameliorating this.

Maintenance stage

Tracey, Speech Therapist: My question is about saliva management. Do you ever prescribe glycopyrronium [an antimuscarinic agent] tablets to patients in earlier stages of Parkinson's (ie not palliative) to manage excess saliva and is it more effective than hyoscine patches? Any contraindications with Parkinson's meds? Dosage?

Nin: If drooling is mild I often use low dose amitriptyline, which has reasonable anticholinergic effects and is less inducing of confusion in the elderly than say benzhexol.

For moderate to severe drooling, I always refer for salivary gland Botox which generally works well. Hyoscine and atropine based patches frequently cause confusion in elderly patients.

Complex stage

James, Parkinson's nurse: Patient bed bound with Parkinson's and dementia, parkinsonism well controlled but clasp knife type rigidity in upper limbs, contracted fingers causing pressure sores to tips of fingers and maceration. Any drug therapies likely to help? Benzodiazepine caused excessive sedation, is baclofen contraindicated/unlikely to help, what about dantrolene? Any advice very gratefully received.

Nin: This is a difficult issue. The finger contractions may be secondary to a non-erosive arthropathy which can occur in Parkinson's or alternatively secondary to dystonic contracture. Either case might respond to Botox injections into the forearm flexors as the treatment of choice.


Lesley, Nurse Manager: How can one differentiate between symptoms of poorly controlled Parkinson's, anxiety attacks and/or side effects of Parkinson's drugs all of which are expressed with similar symptoms? How does one unravel the mystery in an elderly Parkinson's sufferer with moderate dementia?

Nin: The best way to unravel complex patients is a trick the late Professor Marsden taught me in the early 90s. He used to draw out a time chart with the drugs and timings noted. He would then shade in the symptoms either as 'on' or 'off' phenomena. The link between symptoms and drug timings would then become very obvious and the solution to these issues would also be logical, eg if anxiety appeared on the time chart 30 minutes before each levodopa dose was due, it could be classified as an 'off' symptom and the solution would include any of the continuous dopaminergic stimulation (CDS) approaches listed above.


Sarah, Parkinson's nurse: What is your opinion on the use of PEG feeding in advanced/end stage Parkinson's? We sometimes support people with Progressive Supranuclear Palsy (PSP) to have an elective PEG. I tend to assess each Parkinson's case individually. Ethical dilemma!

Nin: I have no problem with use of PEG in advanced Parkinson's. If patients can't take oral intake safely, despite liquidisation, then PEG is the best way forward as we expect them to have a reasonable life span even when they reach that phase of Parkinson's.


Zahid, Consultant: How do you manage advanced Parkinson's in patients who are post op and are on parenteral nutrition with nasogastric (NG) feeding as it interferes with dopamine absorption?

Nin: In this scenario, you could consider replacing some or all of their dopamine with a rotigotine patch. Being transdermal, rotigotine gets round the GI absorption problems.

Rotigotine may not be suitable for older Parkinson's patients at risk of dopamine agonist side effects, eg confusion, hallucinations. In these folks, you will have to adjust the dopamine to compensate for absorption issues, eg try and give it when the parenteral feed is not running, adjust the protein content of the parenteral feed to minimise amino acid competition with dopamine, increase the dopamine dose or give more frequently. 

Length of stages

Luis, Parkinson's UK Helpline Adviser: On the helpline we are regularly asked 'how long someone has' before Parkinson's becomes very problematic, how long before they reach the 'advanced' stages of Parkinson's. Our answer is generally that it is different from person to person, so very hard to answer. What would your answer be?

Nin: It is very different from patient to patient and varies with the kind of Parkinson's (benign tremulous versus akinetic rigid where people fall a lot), the age of onset (younger onset can be both worse, if idiopathic, or more benign if secondary to certain genes, eg PINK1) and whether patients get dementia early.

I generally say we give most patients a very good 5 years, a more variable 5 to 10 years, and after 10 years it all depends on whether they are unfortunate enough to develop dementia or not.

End of life

Alison, Parkinson's nurse: When is it appropriate to open discussion on end of life planning?

Nin: In my view, patients with Parkinson's can be improved with appropriate drug management until they have severe dementia. In this scenario, it is hard to improve the motor state without aggravating the confusion and hallucinations, although the latter can be managed with acetylcholinesterase inhibitors such as rivastigmine.

I would only consider discussion of palliation in Parkinson's disease dementia where there were recurrent infections and poor life quality despite the best medical management.


George, Professor of Health Research: I am interested in the fourth stage and have a question about the role of hospice and specialist palliative care in Parkinson's. Do you think this type of care is appropriate or should specialists in Parkinson's hold the reigns 'until the end of life'?

Nin: I think there is a role for a specialist in Parkinson's to manage patients until they develop moderate to severe dementia. After this, when little can be done to improve the motor state without worsening the mental state, the patient would best be managed by a palliative care specialist with input from a Parkinson's specialist as required.


Tim, Parkinson's UK Advisory Services Manager: We often hear the phrase that people die 'with' Parkinson's not 'from' it. How true do you think this is? Is there a better way that we can respond to people's real fears about the development of the condition?

Nin: I'm afraid that most studies show that Parkinson's takes about 10 years off your life expectancy if you develop it before the age of 65. Older Parkinson's patients fare much better, losing only 2 to 3 years on their normal counterparts.

Drug therapy

Parkinson's UK: For information about any of the Parkinson's drugs mentioned below, please take a look at our pages on drug treatments for Parkinson's.


Gina, Parkinson's nurse: If a patient has a history of Lewy body dementia and is unable to swallow usual levodopa therapy, we usually start them on rotigotine patch. What do you think the initial dose should be and to what dose do you think it's safe to titrate to considering potential side effects and risk of exacerbating symptoms of Lewy body dementia?

Nin: Dopamine agonists are poorly tolerated in patients with Lewy body dementia or Parkinson's disease dementia complex. Caution therefore has to be exercised in using rotigotine in those nil by mouth. You might get away with a very small dose starting at 2mg od and if tolerated going to 4mg.

A safer bet would be madopar dispersible either orally or down an NG tube if the dysphagia is acute.


Daiga, Parkinson's UK National Education Adviser: Is it best to start patients on levodopa as a monotherapy?

Nin: This depends on the age and other medical illnesses. If a Parkinson's patient is under 70 years old, you will probably get away with a dopamine agonist as monotherapy. You might get away with a dopamine agonist in older patients as long as they don't have other medical illnesses, otherwise dopamine agonists have more short-term side effects limiting tolerability such as sleepiness and hypotension.

In patients above 70, I usually consider levodopa as first line therapy. But even then, I try and introduce low dose dopamine agonists, eg rotigotine up to to 8mg, as second line agents.


Sheena, Parkinson's nurse: Is it appropriate to adjust dopaminergic medication when patients present with severely increased anxiety prior to each dose but without significant motor function disruption?

Nin: Anxiety can be related to changes in dopaminergic levels or can be independent of this. Generally when it is related to dopamine, it is in the context of a motor 'off' state. Increasing dopamine levels in this context can reduce the anxiety.

Anxiety can also be secondary to reductions in brain monoamines as part of the parkinsonian process per se as cell types other than dopamine neurones also die. This may be treated with a tricyclic such as nortriptyline. Anxiety secondary to the psychological adjustment of having a Parkinson's diagnosis is best handled by targeted cognitive behavioural therapy.


Liz, Parkinson's nurse: I've read that 24 hour continuous apomorphine infusions lead to the dopamine receptors becoming desensitised. Is there a danger that this could happen with other 24 hour continuous dopamine receptor agonists such as rotigotine and the long acting versions of ropinirole and pramipexole?

Nin: This appears true for apomorphine, although not in all patients, and some groups, especially Italians, are great believers in 24 hour apomorphine. Personally I rarely believe apomorphine beyond the waking hours is useful.

This does not appear to be an issue with the other long acting agonists and may reflect differential binding to the dopamine receptors and/or affinity for certain receptor subtypes (apomorphine is predominately D1 whilst the other agonists are mainly D2).


Mike, Parkinson's nurse: Are there any reliable ways of dealing with biphasic dyskinesias?

Nin: Biphasic dyskinesia or dystonia is due to peak/trough drug fluctuations and the key is to smooth out drug delivery with continuous dopaminergic approaches. You are now spoilt for choice with a range of long acting dopamine agonists.

Other approaches include fractionation of levodopa, use of entacapone +/-, a monoamine oxidase B inhibitor, to incease levodopa half-life.


Rachel, Parkinson's nurse: I see a few Parkinson's patients with biphasic dystonia on levodopa (mainly abdomen, foot and neck regions). I find this symptom very difficult to manage and wondered if you had any suggestions of how to manage this.

Nin: Biphasic dystonia is often secondary to levodopa fluctuation. A variety of continuous dopaminergic approaches may help, including addition of long-acting dopaminergic agonists (eg rotigotine, ropinirole XL or pramipexole MR), addition of entacapone to each levodopa dose and also the use of monoamine-oxidase B inhibitors, such as rasagiline or selegiline.


Rosemary, Pharmacist: I have a patient who is taking co-careldopa 5 times daily, and now on ReQuip XL at top dose taken in the morning. Also on Azilect (if I remember correctly). He finds that the effects are wearing off by about midday. What else can I recommend at this stage? He has tried staggering the dose by having one a bit later on, which does help. Overall though the slow-release product has really helped. He is an active gentleman and it's very important to him to be able to carry on working.

Nin: You can add in entacapone to each of the levodopa doses and if that suits switch the levodopa to Stalevo.


Medhat, Consultant: What's your view on whether starting treatment at diagnosis/early is more beneficial? Do you treat your patients early?

Nin: I am a great believer in treating patients both early and optimally. Most patients presenting to their doctor with parkinsonian motor features have had an extensive loss in dopaminergic neurones. If you carry out an FP-CIT scan on such patients, the deficit is often marked (type 2 abnormalities tend to predominate).

This means it takes a lot of dopa/dopamine agonist treatment in the initial stages to get them back to near normal dopamine levels. I therefore use fairly high dose treatment early on in the disease course and having done so often find that I do not have to do anything more than tweak drugs in subsequent years.

I also think that normalising dopamine levels early allows patients to maintain high levels of phsyical function and once they lose this functionality it is very hard to salvage it. I must stress that this is a personal view and no trial has directly addressed this issue, although trials such as ADAGIO show some supportive data in this direction.


Jayesh, Primary Care Pharmacist: Cost of medicines is high in the NHS. With 3 Parkinson's products coming off patent in the near future, what is your opinion of generic substitution of brand medication in Parkinson's? Is the debate similar in generic versus brand antiepileptic medication and if so is there evidence either way?

Nin: The cost of Parkinson's meds will come down and with the recent price reduction of ReQuip have already come down even before the generics hit the market.

I have no problems with generic formulations but 2 rules need obeying:

  1. I would resist changing a patient on established therapies onto generic versions as there can be profound changes in pharmacokinetics leading to substantial changes in effect.

  2. If the generic does not appear to be working, it should be changed to a more conventional and proven brand.

Impulse control disorder

Liz, Consultant Physician Geriatrics: Do you have a view on use of naltrexone in Parkinson's?

Nin: I have no experience of using the opiate naltrexone for Parkinson's although patients on blogs report improvements in cognition, pain and general wellbeing. I note that the Michael J. Fox Foundation has funded a clinical trial in the use of naltrexone to counteract the symptoms of impulse control disorders in Parkinson's patients on dopamine agonists.


Mel, Parkinson's nurse: Have you any recommendations for treatment and management of symptoms such as apathy and loss of motivation for social activities? I have a gentleman who spends long hours on the computer, mainly on chat forums. Agonists in the past have led to financial problems so he's only on a minimal amount of Madopar. We are thinking about trying antidepressants as the patient is fed up with his behaviour but can't seem to motivate himself to change. His motor symptoms are reasonably stable and controlled.

Nin: This behaviour is known as punding and is suggestive of impulse control disorder (ICD). ICD has an incidence of up to 17% in patients on dopamine agonists, although all current data is on ropinerole and pramipexole.

Approaches include reducing or stopping dopamine agnoists altogether and using levodopa instead (the incidence of ICD with levodopa is substantially less, around 8% in some studies). Sometimes we resort to using atypical antipsychotics, eg quetiapine and clozapine although their effectiveness is purely anecdotal. There is an ongoing trial of naltrexone in ICD and we await the results with interest.

Research

Emily, neurology research nurse: Hi there, I am interested to find out about the recent research that is being or due to be carried out in Parkinson's.

Parkinson's UK: Hi Emily, please take a look at our list of current Parkinson's research projects around the UK which may be looking for participants. We update this list regularly as we hear of new studies.

And our current research pages give information about the research we fund.


Gail, Parkinson's UK education and training officer: As part of a cure are we looking into finding a way to change the structure of the dopamine receptors in the basal ganglia so that they stop dying or even so that they reproduce themselves? Or is this impossible?

Nin: Various teams have been exploring ways to stop dopaminergic neurones from dying, eg using viral vectors to carry neurotrophic growth factors into the basal ganglia part of the brain. Others have looked at stem cell approaches to replace the dead neurones.

There is an ongoing study using the patient's own bone marrow as a source of stem cells to inject into the bloodstream and hope that these migrate into the brain. None of these approaches has yet worked but we live in hope.