James Parkinson

Sunday 30 April 2017

Before the month of April is over I wanted to give a nod to James Parkinson, the eponymous “discoverer” of the disease.

In April 1817, 200 years ago this month, Parkinson published An Essay on the Shaking Palsy, the first description of the disease as a medical condition.  Despite its historical significance, it doesn’t make pleasant reading.  It makes me appreciate how lucky we are that at least there are some ways today of moderating the symptoms even though science is currently unable to halt the progression of the disease.

Parkinson was a surgeon but also a geologist and palaeontologist and, in his early years, something of a political activist.  He had a medical practice in what is now Hackney in London’s East End.

He would have been a child of the Enlightenment and was a contemporary of such leading British scientific figures as James Watt (father of the steam engine which powered the industrial revolution), Humphry Davy (chemist who discovered elements such as sodium, potassium and calcium) and Edward Jenner (inventor of the first vaccine).

It seems unfortunate that his name is associated with a disease that, 200 years on, is still poorly understood, incurable and affects over ten million people worldwide. In contrast, Jenner’s vaccine led to the complete global eradication of smallpox, a horrific and frequently deadly disease. It is said that Jenner thereby saved more lives than any other person in all of human history.

But I have no doubt Parkinson was a good man, fighting for causes such as universal suffrage and publishing many scientific papers.  Probably he would have been surprised that the disease he first identified is still incurable.

Which reminds me: this week I unexpectedly got a confirmation for an appointment in September with a new professor; let’s call him Professor J.  I phoned the hospital thinking there was some mistake but it turns out that, in addition to my next appointment with The (original) Professor I am to see this new specialist in both hereditary movement disorders and clinical trials for Parkinson’s.

So perhaps I am being put forward for some study that just maybe could lead to a cure.

And surely a cure is what James Parkinson would have wanted most.

Side effects

Friday 28 April 2017

I read the list of potential side effects on the leaflet that comes with my box of pramipexole.

Very common (may affect more than 1 in 10 people):

• Dyskinesia (e.g. abnormal, uncontrolled movements of the limbs) 
• Sleepiness 

• Dizziness 

• Nausea (sickness)

Yep, I’ve had all of those.  I read on…

Common (may affect up to 1 in 10 people):

• Urge to behave in an unusual way 

• Hallucinations (seeing, hearing or feeling things that are not there) 

• Confusion 

• Tiredness (fatigue) 

• Sleeplessness (insomnia) 

• Excess of fluid, usually in the legs (peripheral oedema)

• Headache 

• Hypotension (low blood pressure) 

• Abnormal dreams 

• Constipation 

• Visual impairment 

• Vomiting (being sick) 

• Weight loss including decreased appetite 

At this point I realise it’s easiest to identify the side effects I haven’t had, namely the "urge to behave in an unusual way" (I assume you know what this means if it happens...), confusion, oedema and weight loss.  I’ve had everything else in the “common” category.

It’s only when I get to some of the scarier side effects in the “uncommon” category that I start to feel that perhaps it could have been worse.  Fortunately, I don’t identify with any of these apart from the one-off fainting episode a few weeks ago.

Uncommon (may affect up to 1 in 100 people):

• Paranoia (e.g. excessive fear for one’s own well-being) 

• Delusion 

• Excessive daytime sleepiness and suddenly falling asleep 

• Amnesia (memory disturbance) 

• Hyperkinesia (increased movements and inability to keep still) 

• Weight increase 

• Allergic reactions (e.g. rash, itching, hypersensitivity) 

• Fainting 

• Cardiac failure (heart problems which can cause shortness of breath or ankle swelling) 

• Inappropriate antidiuretic hormone secretion

• Restlessness 

• Dyspnoea (difficulties to breathe) 

• Hiccups 

• Pneumonia (infection of the lungs) 

• Inability to resist the impulse, drive or temptation to perform an action that could be harmful to you or others, which may include: 

• Strong impulse to gamble excessively despite serious personal or family consequences.

• Altered or increased sexual interest and behaviour of significant concern to you or to others

• Uncontrollable excessive shopping or spending

• Binge eating or compulsive eating 

• Delirium (decreased awareness, confusion, loss of reality)

I did, however, get the last one on the list.

Rare (may affect up to 1 in 1,000 people):

• Mania (agitation, feeling elated or over-excited)

When I saw The Professor a couple of weeks ago I told him all this and was expecting him to reduce my dosage. 

To my surprise, he told me to stay on the same prescription, presumably on the premise that if the dosage stays the same the body will adjust in time.  In retrospect I guess he was right as most of the side effects have disappeared and I now only display minor Parkinson’s features like the occasional tremor in my right hand.

The one significant problem I still have, other than my eyesight, is disturbed sleep.  I have no problem getting to sleep; it’s just that I usually wake up at 3 or 4am then struggle to get back to sleep.  Hopefully that too will settle down in time.  And on the eyesight problem, he saw no risk in me going ahead with surgery.  More of that to come later….

It will be five months before I see The Professor again.  Perhaps by then the blood tests results will be ready and I can start resolving the hereditary mystery.

I do not know if the drugs will remain effective until then, but what I do reflect on is how serious all this business is… messing with the delicate chemical balance in my brain on a daily basis is not to be taken lightly. 

I try not to obsess over it too much and quietly get on with my life. 

What else can I do?

The network

Saturday 22 April 2017

This morning I met up with a group of complete strangers who all have two things in common: they suffer from Parkinson’s and they are under 60.

There are many Parkinson’s networks and numerous events across the country but these are mostly aimed at elderly people and tend to meet mid-week.  The group I went to see at a café in central London was for younger sufferers, many of whom still work and therefore can only hook up at weekends. 

The first people were about 20 minutes late whereas I was on time so I had some embarrassing moments wandering round asking people if their name was Anne, the organiser of the group.  At one point I even befriended a group of 50-something women who seemed to be old friends, and sipped my coffee with them whilst keeping an eye out.

When the group did start to congregate, somehow it was obvious who they were and I went over and introduced myself.  Aside from more overt signs of unusual movement that I saw in some of the later arrivals, there is a look that Parkinson’s people seem to have.  I think it’s a facial expression that somehow lacks emotion.

In all I stayed for nearly three hours and chatted to perhaps a dozen people.  It was both an uplifting and depressing experience. 

There were standard questions that were both posed and answered.  When were you diagnosed? What were your symptoms? How long did you have symptoms before you were diagnosed? What medication are you on? 

I asked lots more questions too.  How does your husband/wife deal with it?  Do you have any advice for someone recently diagnosed?  How has your disease progressed?  Which hospital do you go to?

I learnt a lot and many people made the point that they get more advice from sharing experiences than from visiting their neurologists every six months who do little more than fiddle with their prescriptions.

It was a diverse group: male and female, thirties to fifties, black and white, employed and unemployed, parents and childless, gregarious and reserved, posh and working class.  Parkinson’s doesn’t discriminate. 

There were some very positive aspects.  There were two women who were five or six years in who looked very well and were leading pretty full lives.  I’ll be happy if I’m like that in five years’ time, I thought. There were a couple of friendly men on my wavelength living not far away from me so we swapped contact details and made a tentative agreement to meet up for a drink in May.

But overall it was depressing.  For the moment I feel pretty good on my drugs, but there were people only a few years ahead of me who seemed to have much more severe symptoms, who were no longer working and who appeared to be struggling to cope.  And there were a couple of older men who, if I am honest, looked pallid and dishevelled.  The other thing I gathered was that even those who were doing well suffered from fatigue most days and often needed afternoon naps. 

For me personally perhaps the biggest challenge about Parkinson’s is the varied progression and not knowing how it will develop.  As someone who likes to plan and be in control I find this difficult.  I heard stories about changes of medication and cocktails of drugs to keep up with the inevitable advancement of the disease, but each one different.   

Will I be as sharp as a razor and still looking great in ten years’ time or unable to work in a year's time?  There is simply no way of knowing. 

The search for a cure

Thursday 20 April 2017

"Experts excited by brain 'wonder-drug'," read the headline on the BBC website this morning.

"MRC scientists discover two repurposed drugs that arrest neurodegeneration in mice" was the slightly more realistic description from the UK Medical Research Council.

I was excited when I first heard about this potential breakthrough for both Alzheimer's and Parkinson's from the Radio 4 Today programme at around 7 this morning.  I rushed into the bedroom holding the radio so that Clara could listen too before I left for work. Part of the reason for the headlines is that one of the drugs, trazodone, is already licensed for use in humans.

On reflection I decided to be cautious about such news. There are clinical trials to be done, the drugs may only have limited effect in humans, work only in special cases or not at all. Medical science is riddled with false starts.

Nevertheless, the more of these headlines I read the greater the chance that one of them will truly fulfil its promise.  And then I certainly will be excited.

A family affair

Sunday 16 April 2017

My 71-year-old mother also has Parkinson’s.

She was diagnosed only about six months before I was though had been suffering more acutely and for longer than myself before receiving the correct medical attention.  As I read back through my earlier writings it seems strange that I didn’t put two and two together with my own situation and I needed a neurologist to tell me what now seems obvious.  I suppose this is because of the subtle nature of the disease that many medical professionals (my own GP included) struggle to diagnose correctly.

Another feature of Parkinson’s is its slow progression.  Unlike having certain types of cancer where you might only have a year or two to live, Parkinson’s is a gradually developing neurodegenerative disease.  In fact, I could easily have already had it for ten or twenty years before the effects became evident.  So, in retrospect, my initial reaction was more extreme than it needed to be: I can wait and see how the disease progresses over the next year or two before making any radical decisions about work and home.

I went to see my mother shortly before Easter so that we could compare notes and empathise with one another.  Being her first-born child, we have always enjoyed a strong mother/son bond, but after an afternoon sitting in the garden in beautiful spring sunshine our shared experience brought us even closer together.  It is a strange coincidence that we were both diagnosed almost within the same year, despite being 24 years apart in age. 

Four generations of our family have now suffered from the disease, so there is almost certainly a faulty gene passed on to me by my mother.  It is likely to be autosomal dominant Parkinson’s in scientific terminology, meaning each child has a 50% chance of getting the gene, and it is not passed down in the sex chromosomes so it affects men and women equally.

The cruel irony is that, despite our shared genetics, one of the reasons that her onset may have been delayed so much was that she was a twenty-a-day smoker for most of her life, and smoking is one of the things known to delay onset of the disease.  As a child I frequently chastised her about her unhealthy habit, whilst I led a squeaky clean lifestyle.  That said, exercise is also supposed to delay onset, but despite being pretty athletic for several decades, I still got symptoms in my mid-forties.  So perhaps luck is a big a factor as anything.

The furthest I have traced back our familial Parkinson’s is to my great-grandfather, William, a GP in Surrey.  He had two sons, the eldest of whom spent many years struggling with Parkinson's until he died in his mid-seventies.  The mystery is why the younger son, my grandfather, did not show any signs of the disease despite living to the grand age of 93.  The faulty gene would have been passed through him to my mother and onward to me.

My mother and I discussed all of this as we sat at the garden table under cloudless skies and amidst budding flowers and greenery.  We speculated as to what could have caused my grandfather’s apparent immunity.  If we could definitively identify some factor that protects against the disease then we might have the seeds of a cure.

The only two factors we could think of were his somewhat hedonistic life as a serial womaniser, and his habit of drinking a glass of single malt whisky every day.  A long shot though these may be (and difficult to assess scientifically) they do, to me at least, seem plausible lines of enquiry. 

The hedonistic lifestyle could indicate an excess to normal levels of dopamine (or equivalently, a reduction in the inhibitory pathways – nothing in this topic is ever simple) caused by some other genetic factors, that compensated for the elevated risk of Parkinson’s.  The plot thickens here as my uncle, who sadly died in his fifties, was a paranoid schizophrenic and, whilst that disease is poorly understood, one of the contributory factors is speculated to be excess dopamine.  So, perhaps my grandfather carried genetic factors that offset each other and passed one set down to my mother and the other set down to my uncle.

The whisky theory seems less likely.  I had a look at the chemical composition of single malts and it is very complicated, so it is conceivable there is some protective chemical in there, but it would presumably be hard to identify.

I related some of this to The Professor when I saw him this week for a check-up and to renew my prescription.

He thought the whisky theory was quite amusing: if only that were true, he mused, it would save a fortune on clinical trials!  He was more sympathetic to my other theory but, short of exhuming my grandfather’s body, it is difficult to gather meaningful data.

He did put me forward for genetic testing and I went to have blood samples taken after the consultation.  Now that I am on the NHS, I was told it would likely take about six months to get the results back.  However, I also participated in a second genetic study this week, going through the strange process of spitting into a tube and the sending my saliva in a FedEx package to a research lab in the US funded by the Michael J Fox foundation.   So I may find out sooner whether I have one of the known genetic mutations, like LRRK2, that contributes to Parkinson’s.

One way or the other I am determined to get to the bottom of what has been a blight on my family for four generations.  And with a daughter of my own plus five brothers and sisters who have a further eight children between them, it is highly probable that some of the next generation are carrying the mutation.  And of course, the faulty gene affects not just those carrying it, but their loved ones too….

Transparency

Sunday 9 April 2017

Three significant things happened this week in relation to my Parkinson's.

Firstly, and perhaps most importantly, I told Rosa.

I had made the decision a few weeks back to tell her in the Easter school holidays.  It wasn't a difficult decision: I was brought up in a very open environment where nothing was ever kept a secret for long and grown-up topics were openly discussed.  I'm a firm believer that children respect their relatives for telling the truth, and telling even white lies only breeds resentment further down the line.  Certainly, as a child I could easily tell when my grandmother was twisting the truth and, despite her many positive qualities, I disliked her for it.  At 12 years old, I was confident Rosa would appreciate me telling her, if not now, then in later years.

It was Sunday morning.

"Rosa, there's something you need to know," I started as she was lazing on the sofa playing Minecraft on her iPad.  "I have a disease in my brain."

She looked at me and smiled, thinking it was a joke.  But she quickly clocked my serious expression, stopped her game and paid attention.

"It's called Parkinson's and you'll find out more about it when you're older.  I have a disease in a tiny part of my brain which in the future will cause problems in moving my arms and legs.  Your Dad will have shaky hands.  I'm taking medicine for it but in a few years' time the medicine will start to wear off."

"Is it causing the problems with your eyes?" she responded.

That's my girl, I thought, and immediately felt vindicated of my decision to tell her.

"Possibly," I said and then explained a little more about the causes of my double vision.

It wasn't a long conversation and we pretty much left it at that.  I told her not to worry and that the symptoms would come on only gradually.   I was nervous before telling her but felt so much better afterwards.   And now I have an excuse for being rubbish at badminton and tennis.

The second big thing to happen this week was that I had my first hallucination.  This falls into the "PFS" category (see previous post on PFS).

I was making lunch in the kitchen when suddenly about a third of my visual field, most of the right-hand side, went completely weird.  I could see normally on the left but on the right was a blank image surrounded by a zig-zag black and white border, a sort of distorted chessboard pattern.

I had no clue what was going on and it was quite scary. What was happening to me?  Would it get worse?  Was I about to go blind?  Would I get faint and collapse like before? Should I call an ambulance?

I sat down as the weirdness continued - it had come on suddenly but appeared not to be getting worse.  Then, after about 20 minutes, it subsided as quickly as it had started.

I quickly flicked on the iPad and within a couple of minutes identified it as a hallucination.  I read that hallucinations can take many forms: voices, visual disturbances and so on, but mine seemed to be a text book case.  I concluded that it was probably caused by the dose of my dopamine agonist being too large, and this was corroborated by other, milder, symptoms I had been experiencing over the past two weeks. These come under the general term of mania: decreased need for sleep, a mind that is racing the whole time, confidence and drive, and a short attention span.  I read further about related mental conditions like bipolar disorder and schizophrenia and the delicate balance of different neurotransmitters in the brain.  And I remain fascinated by the brain's ability to distort reality so readily.

I will speak to The Professor about all of this soon enough, but in the meantime, I only have 1.05mg tablets of pramipexole and don't want to risk the even worse side effects of coming off my medication abruptly, so I live hoping I do not have further episodes like this....

Thirdly this week I participated in my first Parkinson's study. The study was aimed at genetic analysis of people like myself with young onset or familial Parkinson's in the hope of identifying genetic factors that either cause or mitigate the disease.  This in turn could help identify new treatments, not just for the 5-10% of people with genetic Parkinson's, but for all sufferers.

I was extremely impressed with the professionalism of the study coordinator and the accompanying doctor, who carefully explained everything to me, stressed the lengths they go to around information security, and were friendly and positive.  The whole process only took about two hours: blood samples, various questionnaires, and some clinical tests (which I am now becoming quite familiar with).  They even recorded some of the examination on video for quality control.  "Don't show that to my daughter. I'll never hear the end of it," I joked.

The only downside was that I won't get to see any personal results of the analysis as all the data are anonymised.

But I was glad to have done my bit, however small.  They thanked me heartily and I thanked them more in return.  After all, there is a slim chance that their study could help save my life, or the lives of future generations....