“Why Doctors Make Mistakes” Article

The author of a very good book “”How Doctors Think” has written a short article on “Why Doctors Make Mistakes” for the upcoming issue of AARP The Magazine. A copy of that article is below. Fuirther down is an email from May ’07 (sent to the local support group; not posted here), around the time with Dr. Groopman’s book was published. The PBS Newshour interview is still available (the longer RealVideo version).

http://www.aarpmagazine.org/health/why_ … takes.html

Why Doctors Make Mistakes

By Jerome Groopman, M.D.
September & October 2008
AARP The Magazine

Too often, physicians make snap decisions. Here are three questions to help get you to the right diagnosis

Not long ago I spoke with a middle-aged woman whose mother had been misdiagnosed with Alzheimer’s disease. The elderly woman’s memory was fading, and her family was close to admitting her to a nursing home. Luckily, the family decided to get a second opinion from a neurologist at a different hospital. It turned out the woman did not have Alzheimer’s at all but, rather, vitamin B12 deficiency, a well-recognized cause of dementia. Her mild anemia, also due to vitamin B12 deficiency, had been written off by her internist as being due to “old age.” Injections with the vitamin fully reversed the anemia and restored her thinking.

Unfortunately, medical misdiagnosis is not a rare phenomenon. About 15 percent of all patients are misdiagnosed, and half of those face serious harm, even death, because of the error. Contrary to the general impression that most misdiagnoses result from a technical foul-up, such as mislabeling someone’s X-ray or mixing up a blood specimen in the laboratory, most cases are due to mistakes in the mind of the doctor.

Most errors are due to mistakes in the doctor’s thinking.

How do doctors think through a case? Making an accurate diagnosis involves arranging the information from the patient’s symptoms—findings from physical examination and laboratory tests—into a pattern. A doctor then superimposes this pattern onto a template of the typical case that exists in his or her mind. But this effort at pattern recognition doesn’t always work. Why not?

First, there may be incomplete or misleading information. Patients may not feel comfortable reporting all their symptoms to a doctor—or, as studies show, physicians may prematurely cut off a patient who is reciting his or her problems (in fact, research reveals that most physicians interrupt a patient within 18 seconds of beginning an interview). Second, pattern recognition is difficult because cases may not be “typical.” This means that diseases can have different manifestations, sometimes quite subtle, because every individual is different. Most significant is how the doctor selects the clinical elements, weighs their importance, and arranges them in his or her mind, a process that can result in several different patterns, leading to quite different diagnoses.

There are three major cognitive mistakes that can occur in the mind of the doctor and lead to misdiagnosis. The first is termed anchoring, meaning the tendency to grab on to the first symptom, physical finding, or laboratory abnormality. Such snap judgments may be correct, but they can also lead physicians astray. A second common cognitive error is termed availability. This refers to the tendency to assume that an easily remembered prior experience—what is most readily available in the physician’s memory—can explain the new situation he or she is trying to diagnose. The third mistake in thinking is termed attribution, and this accounts for many of the misdiagnoses in the elderly. Attribution refers to the tendency to mentally invoke a stereotype and “attribute” symptoms to it. Alas, often this stereotype is a negative one, such as an older person who is seen as a complainer, a hypochondriac, or a person unable to cope with his or her naturally declining abilities. The doctor ignores the possibility of an illness not specifically linked to “old age,” as in the case of the woman with B12 deficiency. Imagine how much it would have cost in physical resources—not to mention emotional ones—to keep her in a nursing home for the rest of her life.

What can patients do to help prevent medical thinking from going astray? I have formulated three simple questions to ask. It is quite appropriate for patients and their families to pose these questions to their doctor when he or she is making a diagnosis.

1. “What else could it be?” This question helps to prevent an anchoring error or an availability error, where a diagnosis is formulated too quickly in the physician’s mind because it corresponds to the initial symptom or abnormality (anchoring) or because it is most familiar to the doctor (availability).

2. “Could two things be going on to explain my symptoms?” In medical school doctors are taught to be parsimonious in their thinking, meaning they are taught to identify a single cause to explain a variety of complaints and symptoms. But sometimes a patient can have two medical problems simultaneously. Physicians sometimes stop searching once they find an initial problem, even if the patient does not fully recover.

3. “Is there anything in my history, physical examination, laboratory findings, or other tests that seems not to fit with your working diagnosis?” All physicians tend to discount information that seems to contradict their hypothesis. This bias can lead a doctor down the wrong path; his or her anchor diagnosis may be so firmly fixed that this leads to ignoring contradictory data.

I have found that smart and dedicated physicians are able to explain their thinking, and they are able to put into clear and accessible lay language how they arrived at their working diagnosis. In some instances these questions may cause the doctor to go back and reexamine assumptions, to think again, and to come up with a different, and now correct, diagnosis. All doctors want the best treatment for their patients, and the best treatment involves the most open-minded thinking.

Jerome Groopman, M.D., is the author of the New York Times bestseller How Doctors Think (Mariner Books, 2008).


Date: Tue, 15 May 2007 22:39:34 -0700
To: Local Support Group
From: Robin Riddle <[email protected]>
Subject: “How Doctors Think” Author on PBS Newshour

There was a great interview tonight (5/15/07) on the Newshour with Jim Lehrer on PBS with a physician who wrote a book called “How Doctors Think.”

You can find it online at this web address http://www.pbs.org/newshour/health/ and click on “Physician-Author Takes Readers Inside Doctors’ Minds.”

If that doesn’t work, then go to http://www.pbs.org/newshour/ and click on “Doctor Explores Decision-making and Diagnoses.”

(Note that the RealVideo version is an extended interview, longer than what was shown on TV. The extended interview is more interesting as it has more examples. You might be able to link directly to the extended video version by clicking here:
http://www.pbs.org/newshour/video/jan-j … opman.html )

Here’s a brief description of the interview from the Newshour website: “Harvard Medical School’s Dr. Jerome Groopman came up with the idea for his book ‘How Doctors Think’ while watching medical students make snap judgments while diagnosing patients… Many medical mistakes occur because doctors make snap judgments… Groopman talks about how doctors get diagnoses right and sometimes wrong.”

Dr. Groopman’s research shows that 15% of all people are misdiagnosed. He indicated that some experts believe the correct figure is 20 to 25%. In half of those cases, serious harm results.

He lists three kinds of thinking errors, and says that medical students, residents, and senior physicians are not taught to be aware of these errors. He also says whether the doctor likes or doesn’t like a patient can play a role in making a misdiagnosis.

Dr. Groopman speaks candidly about the fact that some misdiagnoses are fatal. And he discusses his own experience as a patient who had a hand problem, saw 6 surgeons, and got 4 different diagnoses. The doctor himself was a victim of medical misdiagnosis.

What should patients do to help ensure their doctor reaches the right diagnosis? He says it’s important for patients to know how doctors think. Some questions are important to ask the doctor when the doctor gives the diagnosis and later when the situation doesn’t improve:
* What else could it be?
* Could two things be going on at once?
* Have you found anything (any lab test, xray, physical finding) that contradicts what seems to be the diagnosis?

He had specific advice for parents: parents should tell doctors what their worst fears are. This needs to be addressed.

‘When I kept falling over, my wife said I was drunk’ – one man’s battle with PSP

This is a good article in the Daily Mail (London) about a man struggling with progressive supranuclear palsy.

The PSP Association’s chief executive is quoted as follows:

“PSP is a devastating neurological terminal illness, which first steals a person’s balance, then progressively robs them of their ability to walk, talk, eat, drink and see, yet they remain mentally alert. It can best be described as a living hell.  Most people have never heard of this illness, and don’t recognise its symptoms – even among the medical profession. In its early stages, a lot of people feel lethargic and down, and may wrongly be given antidepressants. These may help some patients, but the side-effects may make others feel worse. In one in three cases of misdiagnosis, people are told they have Parkinson’s Disease and given drugs which do not help and have unpleasant side-effects such as hallucinations.”




‘When I kept falling over, my wife said I was drunk’: One man’s battle with the disease that killed Dudley Moore
By Lesley Gibson for MailOnline
UPDATED: 21:55 EST, 18 August 2008

On a good day, Ray Nind falls five times. In the past year, he’s been rushed to hospital six times to be treated for the resulting injuries – usually cuts to the back of his head that need stitches.

‘When I first began falling, people thought I was drunk,’ says Ray, 56. ‘Even my wife thought I had been drinking. She kept asking if I’d “had a few” on the quiet, but I honestly hadn’t. I didn’t know why I kept falling. Now, fortunately, everyone who knows me is aware I fall because I’m ill.’

Until recently, Ray, who lives in Ilford, Essex, ran a building business, employed more than 20 staff and drove a three-litre Jaguar. ‘Now I just watch TV all day,’ he says. ‘It’s all I can do.’

His wife Jenny, 54, worked alongside him looking after the secretarial side of the business, but is now his full-time carer.

Ray has a brain disease called Progressive Supranuclear Palsy (PSP) for which there is no treatment or cure. One in three people is predisposed to it because of a genetic fault.

While 4,000 Britons are known to be living with PSP, experts believe the real number is nearer 10,000.

The condition affects those over 40, and equal numbers of men and women.

Daily Mail diarist Nigel Dempster died from it in July 2007, aged 65. Comedian Dudley Moore also died from the condition, in March 2002, aged 66.

The cause is unknown – blows to the head and environmental toxins are possible triggers – but the mechanism is understood.

Basically, cells in the brain produce too much of a certain protein, called tau; this causes neurons (nerve cells) to die. Messages can no longer be sent from the brain to certain muscle groups, especially those affecting the legs, speech, swallowing and vision.

The part of the brain that controls mood and personality may also be affected, leading to patients becoming unusually depressed, withdrawn and apathetic, or aggressive and demanding. The condition does not affect intelligence or memory.

A cruel and unknown disease

PSP is a cruel disease – life expectancy is five to eight years from onset. Although there is no cure or treatment for the condition, drugs can be given to alleviate certain symptoms in some patients.

The PSP Association is battling to make both the public and the medical profession more aware of this devastating illness because without early and accurate diagnosis, patients may be given inappropriate drugs and cannot get the information and support they need.

Chief executive Jane Hardy says: ‘PSP is a devastating neurological terminal illness, which first steals a person’s balance, then progressively robs them of their ability to walk, talk, eat, drink and see, yet they remain mentally alert. It can best be described as a living hell.

‘Most people have never heard of this illness, and don’t recognise its symptoms – even among the medical profession. In its early stages, a lot of people feel lethargic and down, and may wrongly be given antidepressants. These may help some patients, but the side-effects may make others feel worse.

‘In one in three cases of misdiagnosis, people are told they have Parkinson’s Disease and given drugs which do not help and have unpleasant side-effects such as hallucinations.’

Personality change

It took ‘only’ 18 months for Ray to receive his diagnosis – shorter than the average diagnosis time of four years. But, initially, his private neurologist put his symptoms down to a stroke.

When Ray’s symptoms worsened, Jenny kept saying it couldn’t be a stroke, but her husband insisted that ‘consultants are supposed to know best’.

In fact, it had been Jenny who first realised something was wrong, in 2001 when Ray started tripping over kerbs, and steps, for no apparent reason.

‘His elderly father had died just before that and I thought he’d been drinking to numb his grief – yet he insisted he hadn’t,’ she recalls.

But it was the change in his personality that alarmed her most. Normally very sociable, Ray wanted to spend more and more time on his own and lost interest in going out.

‘All he wanted to do was watch TV all day,’ says Jenny. ‘Even his choice of programmes had changed. He started watching rubbish, such as low-life chat shows. He also became unusually irritable.’

Behaviour change

Three years ago, she woke up at 5.30am to find Ray had disappeared, taking the car. ‘I was so worried – this just wasn’t the kind of thing he did. When he hadn’t returned at 6am I called him at work.

‘He answered and explained he’d got up at 2.30am and, not realising what time it was, had set off for work. The police had stopped him and accused him of driving erratically. Convinced he’d been drinking, they’d taken him back to the cells, where he’d spent two hours before they released him and he went in to work.’

It was only when Ray’s colleagues voiced their concerns that he consulted a neurologist in April 2005. The doctor agreed something was wrong but was perplexed because brain scans showed no abnormalities.

This is not unusual – PSP cannot be detected on a brain scan. Even when, a few months later, Ray developed slight paralysis and began slurring his speech, it was blamed on a stroke.

Physical damage

Ray was still working part-time, but his business was failing, partly because he was ill and could not give it the attention it needed. His falls were now occurring on a daily basis, too.

‘He’d fall getting out of the car, or opening the boot – always backwards or sideways,’ remembers Jenny. ‘His eyes were also different, as if he were looking up at the ceiling instead of straight at me.’

Ray’s illness was causing his body increasingly serious damage. He fell down some stairs and fractured his vertebra. He scalded himself trying to fill a hot water bottle to ease the pain and needed specialist burns treatment.

In September 2006, after he had fallen on the living room coffee table so badly he needed several stitches, the couple refused to believe the stroke theory any longer.

At their nearest hospital in Romford, Essex, an NHS neurologist examined the numerous MRI scans and notes from the previous few months. He asked Ray to look up and down, count his fingers, walk in a straight line, and questioned him on his physical capabilities.


As PSP does not show up on scans, specialists use symptoms such as regular backward falls and an upward gaze to check for the illness. Finally, five years after the initial symptoms and 18 months after first seeing a doctor, Ray was correctly diagnosed.

Ray recalls: ‘We’d never heard of PSP so Jenny looked it up on the internet when we got home. As we read the information, all my symptoms suddenly made sense. The falling backwards or sideways, slurred speech, changes in personality and difficulty gripping and swallowing were all listed.’

But Ray also read that the illness would worsen, until he became bed-bound and unable to talk. Because of difficulty swallowing, aspirational pneumonia, when food literally goes down the wrong way, is a real problem; it can cause infection in the lungs, which is often fatal.

Ray says: ‘My first thought was: “I’m going to die much sooner than I want to.” Aside from that, I was too shocked and numb to feel anything else. For weeks, we dressed, ate and went about our daily business like zombies. Gradually, we accepted the news.’

With inspiring courage and stoicism, Ray says he has come to terms with the fact he is dying. His mother died in 1994 from motor neurone disease – a neurological disorder with similarities to PSP. But there is not believed to be a genetic link.

‘Jenny and I both realise there’s no point in being in denial,’ he says. ‘There’s no point in saying I’ll get better, because I won’t. So we’ve faced facts. We know I will die, but we try not to think about it.’

However, it isn’t easy. Ray aches all over because the muscles he cannot use properly cramp. His eyes are dry and sore because he cannot blink, and he has double vision because his eye muscles do not get messages from the brain.

With his slurred speech, saying more than a few words is tiring. He struggles to grip his cutlery and needs a wheelchair for outings. ‘It’s very annoying being unable to do anything for myself,’ he says.

Raising awareness

There are times when Ray forgets how incapable he is, and gets up to do something, only to fall and hurt himself. Six weeks ago, he cut his head again after going out unsupervised in his electric wheelchair and falling out.

For Jenny, of course, caring for Ray is a heartrending job. The outgoing, independent man she married 28 years ago must be dressed, washed and fed.

Yet she is incredibly chatty, cheerful and doggedly determined to see the bright side in everything, even if she is despairing inside. ‘We haven’t been to casualty yet this year, and that’s great,’ she jokes.

Although there is no treatment for PSP, Ray takes anti-depressants and sleeping tablets. The couple also have the support of a multidisciplinary team arranged by their GP, including an occupational therapist who has provided them with disability aids, a speech and language therapist to help with communication, and care assistants to help Jenny.

The couple have planned for the future as much as they can. ‘We’ve set up wills and cleared our debts, apart from the mortgage,’ says Jenny. ‘And thanks to the GP, we have the support we need. I just hope that our story is a lesson to other people who might be affected by PSP.

‘We want to make people aware of this illness so they don’t go through what we did. We spent months struggling without any help or support because Ray was misdiagnosed.

‘Although this disease is incurable, knowing what was wrong with Ray was such a relief. It meant we could make sense of his symptoms and get some help.’

For Ray, it’s simply a case of trying to stay strong for as long as he can. ‘It’s very frustrating. I used to be proud to be the one that looked after the family, and now there’s been a complete role reversal. I’m an old-fashioned man and it’s been hard to accept that, but I’ve had to.’


Non-motor symptoms in PD- panel Q&A

The Parkinson’s Disease Foundation (PDF) hosted a symposia on Parkinson’s on July 18, 2008.  The overall topic is “Mind, Mood and Body: Understanding Nonmotor Symptoms of PD.” Here’s a link to the archived recording of the symposia:


There was a terrific question and answer session with panelists.  The panelists were:

• Peter LeWitt, M.D., Henry Ford Hospital
• Doree Ann V. Espiritu, M.D., Henry Ford Hospital, geriatric psychiatrist
• Edwin B. George, M.D., Ph.D., Wayne State University School of Medicine
• John L. Goudreau, D.O., Ph.D., Michigan State University, neuro-ophthalmologist
• Matthew Menza, M.D., Robert Wood Johnson Medical School
• Ronald F. Pfeiffer, M.D., University of Tennessee Health Science Center, neurologist

I’ve copied below notes that I took from the Q&A session with the panel.  (Time markings refer to the time in the recording, should you want to check out the original source yourself.)


Question:  (43:57)  Relationship between impulsive behavior and PD?

Answer by Dr. Menza:  Impulse control disorders are major personality changes.  This happens largely due to medication.  Can happen with Sinemet but is more of a problem  with dopamine agonists.  Please talk to your physician about these problems as they are treatable.

Answer by Dr. LeWitt:  There is no profile for who is going to get these.  These behaviors can begin years after meds begin.

Question:  (46:38)  Are hallucinations caused from the disease or the meds?

Answer by Dr. Espiritu:  Some of the meds can cause hallucinations.  When dementia starts to develop, the risk for hallucinations increases.

Answer by Dr. George:  People with DLBD (diffuse Lewy body disease) can develop hallucinations without being on medications to trigger them.  We don’t have the answer how much pure PD in the absence of meds can trigger hallucinations.

Question:  (49:05)  Is losing sense of smell 20 years prior to diagnosis a coincidence or is this connected?

Answer by Dr. Pfeiffer:  Loss of sense of smell is a common and early finding in PD.  Many may not realize it.  This can happen much earlier than the onset of motor symptoms.  Twenty years is a long time but this could still be seen as being part of PD.

Question:  Any suggestions for erectile dysfunction when Viagra and similar meds don’t help?

Answer by Dr. Pfeiffer:  (50:27)  There are a variety of methods that can be used to treat ED, including injections, vacuum devices, rings, etc.  Urologists know about this.

Question:  What’s the impact of caffeine on PD?

Answer by Dr. LeWitt:  A study showed that neither PD tremors or essential tremors are worsened by caffeine.  (52:12)  Doesn’t seem to be any downside of caffeine.  Long term studies show that caffeine intake correlates with less progression of PD and lower incidence of PD.

Question:  What can we do about dizziness?

Answer by Dr. LeWitt:  Don’t accept the word “dizziness.”  Pin down what this means.  “Dizziness” is non-specific.  No medication can really help with this.  Is this:  low BP, inner ear problem, balance mechanism problems?

Question:  (54:19)  Is there a connection between nightmares and PD?

Answer by Dr. Menza:  Clinically, we worry that someone who develops bad nightmares may be in the early stages of developing hallucinations during the day.  So we want to know if there’s any problem during the day.  And, there are a number of sleep disorders that can include nightmares.

Question:  (55:37)  Is there any evidence that Seroquel is any more effective than Risperdal in treating hallucinations and behavioral problems in late stages of PD?

Answer by Dr. Menza:  Seroquel and Risperdal are antipsychotics.  Risperdal is a drug that I would not encourage those with PD to use.  Most of those with PD will not tolerate Risperdal.  It makes their PD worse.  There may be exceptions.  I don’t know if there’s any efficacy difference but there’s a tolerability difference.

Question:  (58:19)  Does DBS help with pain?

Answer by Dr. George:  Good question.  We don’t know.  There is some reason to think it would help.  But we usually wouldn’t use that sort of symptom as an indicator to go ahead and do this surgery.

Question (by Dr. Menza):  What do you think the relationship between pain syndromes and depression in PD is?

Answer by Dr. George:  (59:38)  Pain complaints are a major issue in those with depression.  They can certainly co-exist.

Question:  What’s your experience in using Ritalin to treat the symptoms of PD?

Answer by Dr. Espiritu:  (00:20)  Ritalin is a medication given for attention deficit disorders.  In geriatric patients, Ritalin (in the morning) can be used to augment an antidepressant (such as Zoloft, Paxil); it helps with fatigue and alertness.  There are no studies of Ritalin in PD.  Sometimes it is considered where there is extreme fatigue.  Another med that is used is Provigil.  A possible drawback can be anxiety, especially if the patient is already anxious.

Question:  (02:00)  Correlation between young-onset PD and seizures?

Answer by Dr. LeWitt:  Not aware of any connection.

Question (by Dr. LeWitt):  What is the connection between exercise and doing well with PD?  Is there evidence of this?

Answer by Dr. LeWitt:  There is lots of animal research (in animals with PD) that shows that exercise helps PD motor symptoms.  The evidence is convincing.

Answer by Dr. Pfeiffer:  In one study, the human equivalent would be a marathon a day for the amount of exercise the mouse got.  But there are human studies coming out of the Univ of Memphis that show that exercise helps.

Question:  Can loss of sense of smell be in both men and women?

Answer by Dr. Pfeiffer:  Yes, both men and women.

Question:  (04:15)  My wife is losing her teeth.  Her dentist told her it is due to the lack of saliva in the mouth from medication taken for PD.  Is this true?

Answer by Dr. Pfeiffer:  There is a literature on dental problems in PD, but it’s confusing.  Some reports say that people with PD have more dental problems due to the absence of saliva and the change in saliva pH.  On the other hand, there have been studies (one out of Japan in particular) showing that PD patients have better teeth.  It seems possible that absence of saliva could leave to poor dental care, gingivitis, and ultimately to loss of teeth, though this isn’t a common problem.

Answer by Dr. Goudreau:  (05:39)  The dentist could be referring to anticholinergic meds (such as Artane) which can dry up saliva quite remarkably.

Question:  (06:03)  Why is there an increase in muscle cramps in PD and what is recommended?

Answer by Dr. George:  Are we talking about dystonia or simple muscle cramps?  PD patients can get dystonic contractures which can occur as a result of medication (peak dose) and as a wearing-off effect of medication.  We typically see people with dystonia of the feet early in the morning from wearing-off of PD meds.  This can be confused with nocturnal leg cramps.  There could be a separate problem of neuropathy.  Have to sort out what sort of cramping the patient is experiencing.

Question:  Any contraindications for caffeine and Azilect?

Answer by Dr. LeWitt:  None known.  There are some foods to avoid with Azilect (rasagiline).  (07:51)

Question:  Treatment of compulsive behaviors.  If off agonists and behaviors persist, is the only choice to reduce Sinemet?

Answer by Dr. Espiritu:  The compulsive issues are very destructive in relationships.  After you’ve tried to decrease the meds that potentially cause these behaviors, and the behaviors persist, we need to take into consideration other meds, such as those for bipolar disorders.  For example, Depakote and lithium.  But these meds contribute to tremor and can worsen PD symptoms.  Antipsychotics are another choice to calm the behavior.  Have the patient see a therapist.

Question:  (10:15)  Is there a time late at night when you shouldn’t exercise?

Answer by Dr. Menza:  As best I understand, you can exercise any time you want.  It always helps with sleep.

Question:  Is sleepiness a biomarker for PD?

Answer by Dr. Menza:  As far as I know, no.

Question:  (11:05)  How do you treat the loss of libido in women?

Answer by Dr. Espiritu:  There was once talk about a nasal spray that was being tested in a small study in women.  There are many psychological issues that need to be addressed with regard to one’s libido.

Question:  (12:37)  Heavy-sweating in PD.

Answer by Dr. Pfeiffer:  40% of PDers have problems with increased sweating.  Usually face, neck, and maybe chest and arms.  Can be precipitated by activity (too much tremor or dyskinesia).  This can happen out of the blue.  Sometimes clothes have to be changed.  Presumably this occurs because of autonomic dysfunction.  This is bothersome but not dangerous.  Treatment is problematic.  I haven’t found an effective treatment for this — not botox, not propanolol.  If it’s due to dyskinesia or wearing-off, controlling PD symptoms should be addressed.

Question:  (15:30)  Impairment in visual-spatial processing.

Answer by Dr. Menza:  Complicated to sort out what in your environment you are going to pay attention to.  Maybe some of the AD drugs will help (maybe Namenda).  Obsessive-compulsive disorder is sometimes seen in PD.  It’s an anxiety disorder.  Treatment in PD is the same as treatment for OCD without PD.

Question:  (17:54)  Creatine, CoQ10, etc.

Answer by Dr. LeWitt:  No effectiveness seen in CoQ10.

Question:  (18:40)  How do you get involved in trials?

Answer by Dr. LeWitt:  See pdtrials.org (he said .com but it’s .org)

Question:  How can we slow PD?

Answer by Dr. LeWitt:  We don’t know.

Question:  What about gene therapy?

Answer by Dr. LeWitt:  There are several studies going on and some planned for in the US.

Question:  (20:40)  Can swollen ankles be caused by PD or PD meds?

Answer by Dr. George:  This can be a side effect from dopaminergic agents.  Also, there are changes in vascular tone that can occur in PD.  Other things can cause this such as heart failure.

Question:  What do you know about Azilect?  Can this halt progression of PD?

Answer by Dr. Pfeiffer:  There’s a clinical trial that’s been going on for several years now in Azilect.  News has been coming out about this trial.  The formal report has yet to be released.  Pre-clips have been released.  We don’t know which 2 of the 3 study objectives were met.  In August, the study results will be presented at a meeting in Spain.  At this point, the answer is “maybe.”

Question:  (23:40)  What is the danger of discontinuing Sinemet suddenly?

Answer by Dr. Goudreau:  One danger is NMS (neuroleptic malignancy syndrome).  Life-threatening syndrome.  This is rare.  Other danger is the risk associated with profound immobility that insues from stopping Sinemet:  increased risk of deep vein thrombosis, respiratory infections, etc.  “Drug holidays” have been discontinued because of these risks.  Sudden discontinuation of Sinemet is not recommended.

Question:  My “get up and go” has gotten up and went.  Can you address this?

Answer by Dr. Espiritu:  Apathy is common in PD.  Different from depression.  In apathy, there’s no drive to do anything.  Need to rule out depression.  Talk to a therapist about this.  Use of stimulants has not been studied.

Answer by Dr. LeWitt:  (26:33)  Medication trial in apathy is going on in a small way.  It’s not treated with anti-depressants.

Question:  Benefits of metronome therapy?

Answer by Dr. LeWitt:  This is undergoing research now.

Question:  (27:28)  What is being done to help with cognitive problems?

Answer by Dr. LeWitt:  There are some medication trials being studied for this.

Question:  Neupro patch.

Answer by Dr. LeWitt:  It will likely be returning to the market in the US next year.  Benefits of over-night effects.

Question:  How does someone decide to stop driving?

Answer by Dr. George:  There are many non-motor symptoms that affect driving.  Speak with your physician if you or your family has concerns about driving.  Often an occupational therapist can do a driving evaluation.

Question:  Music therapy.

Answer by Dr. LeWitt:  This is part of the symposium in September.  People with gait problems have been able to overcome these problems with music.

Question:  Balance and walking problems due to PD.

Answer by Dr. Pfeiffer:  Multi-factorial due to the case.  Does falling and hitting one’s head disrupt the inner ear?  Probably.  Balance problems occur later in PD.  If it occurs early in PD, you ares probably dealing with a Parkinson’s Plus syndrome.

Answer by Dr. George:  Antivert is a drug that suppresses the balance organ in the inner ear.  This drug can make your balance worse in PD.

Answer by Dr. Goudreau:  Important to determine if balance problems only occur when levodopa wears off.  Many things contribute to balance problems, such as a pinched disc, impaired vision due to cataracts, etc.  A physician needs to review this.  Balance is a common problem in PD but other reasons should be considered.


Visual Impairment in PD

The Parkinson’s Disease Foundation (PDF) hosted a symposia on Parkinson’s on July 18, 2008.  The overall topic is “Mind, Mood and Body: Understanding Nonmotor Symptoms of PD.” Here’s a link to the archived recording of the symposia:


One of the panelists, Dr. John Goudreau, gave a good, albeit short, presentation on the topic of “Visual Impairment in Parkinson’s Disease.”  He is a neuro-ophthalmologist at Michigan State University.

Copied below are the notes I took from his talk along with relevant Q&A.  (The time markers refer to the time in the recording, if you want to refer to the original.)



Speaker:  John L. Goudreau, D.O., Ph.D., Michigan State University

Visual impairment is a common complaint in PD and ageing.  Many of the non-motor symptoms are common in ageing.


  • decreased acuity
  • “tired eyes”
  • irritation (such as grittiness) or pain
  • blurred or double vision
  • visual-spatial confusion

Functional impact:

  • decreased reading
  • decreased driving
  • risk factor for dementia and visual hallucinations
  • contributing factor in falls

Causes of visual impairment in PD:

  • decreased blinking and dry eyes syndrome
  • quality of tears is poor
  • convergence insufficiency
  • loss of retinal dopamine (causing loss of color discrimination and loss of visual contrast sensitivity)
  • brain pathology of PD (causing visual-spatial impairment)

Subtle changes in vision are apparent in early PD.  Is this a biomarker for early PD?  (38:45)  We could introduce neuroprotective drugs earlier.

Changes in retinal function progresses in parallel with PD.  Is this a biomarker for disease progression?

Treatment of impaired vision:

  • hydration (aqueous drops 4-5 times/day, viscous or gel preparations, increase humidity in house, punctal occlusion for severe cases)
  • prisms
  • use of near vs. distance glasses
  • dopaminergic medications can help vision (and vision may fluctuate along with these meds)  (41:30)

Q&A with the Panel

Question:  Any link between PD and pal optic nerves (sp?)?

Answer by Dr. Goudreau:  The optic nerve fiber layer is not the one that seems to degenerate in PD.  The interconnection cells are degenerated in PD.

Question:  (56:40)  Severe double vision.

Answer by Dr. Goudreau:  With any of these non-motor symptoms, PD may not be the only explanation for them.  Severe double vision can be due to PD.  Need to see an ophthalmologist.  This can be treated with prisms.  Cover up one eye when reading.  Alternate the patch.

Question:  (14:36)  How do you do an eye exam in someone who has difficulty communicating?

Answer by Dr. Goudreau:  There are limits.  But there are some basic parts of the exam that could probably still be done.

Question:  (15:30)  Impairment in visual-spatial processing.

Answer by Dr. Goudreau:  Challenging area.

Emotional and Cognitive Aspects of PD

The Parkinson’s Disease Foundation (PDF) hosted a symposia on Parkinson’s on July 18, 2008.  The overall topic is “Mind, Mood and Body: Understanding Nonmotor Symptoms of PD.”  Here’s a link to the archived recording of the symposia:


The second speaker, Dr. Matthew Menza, gave a good presentation on the topic of “Emotional and Cognitive Aspects of Parkinson’s Disease.”

Even though this presentation was focused on PD, some references are made to LBD.  And, of course, there are emotional and cognitive aspects to all of the atypical parkinsonism disorders.

The most important thing I got from Dr. Menza’s presentation is that SSRIs should *not* be considered as the first line treatment in dealing with depression in PD.  A recent study showed that an old antidepressant, nortriptyline (Pamelor), performed better than Paxil, an SSRI.  Other drugs that are similar to nortriptylnie are Cymbalta and Effexor.

Of the atypical parkinsonism disorders, the only antidepressant that has been studied is Elavil (amitriptyline) in PSP.  Otherwise, I’m not aware of any studies.  You might take this recent PD research to your MD to find out if his/her recommendation would change based upon the new info.

Dr. Menza spent some amount of time on antipsychotics.  He explained that there was good data to recommend Clozaril and that in some studies Seroquel performed no better than the placebo.

He did talk about Lewy Body Dementia a couple of times, but I didn’t think his description was very good.  (Dr. Menza is a neurologist and psychiatrist.)

These are my notes from his presentation and his answers to the questions directed to him.  Of course it’s much better to watch the video yourself.


Robin’s notes from:

Emotional and Cognitive Aspects of Parkinson’s Disease
Matthew Menza, M.D., Prof. of Psychiatry and Neurology, Robert Wood Johnson Medical School

Non-motor symptoms of PD include:
* sleep disturbances, fatigue, and excessive daytime sleepiness
* depression
* drug reactions, including psychosis and impulsivity
* mild cognitive impairment to dementia

The non-motor symptoms have become the focus of research because they are so important to how patients feel day to day.

Depression:  about 40% have some.  It has a major impact on quality of life and functioning (faster progression of motor symptoms; greater decline in cognitive skills; greater decline in ability to care for self).  Depression often precedes the PD diagnosis.

Symptoms of depression include:  sadness, lack of appetite, sleep problems, lack of interest and motivation, fatigue, crying spells, etc.  Some of these symptoms are seen in PD without depression.  (6:22)

Depression is very inter-related with anxiety (worrying about things in an excessive way).  Anxiety is a common symptom in PD.

What causes depression in PD?  Probably a mix of neurochemical changes in the brain that accompany PD and the stress of living with an illness.

We encourage people to get involved in support groups.  There’s a lot of knowledge in SGs about handling day to day problems.  SG members may have common wisdom that MDs may not know about.

Try relaxation techniques to help yourself forget worries and get to sleep.  Even counting sheep.

Psycho-therapies are being modified and written expressively for those with PD.  Best to find a psychiatrist or psychologist who has experience with PD.

Exercise is a good treatment for depression.

NIH funded an 8-week trial of PD and paroxetine CR (an SSRI), nortriptyline (a tricyclic), and placebo.  This is the largest and first of placebo-controlled studies on antidepressants and PD.  This study is not yet published.  (Other studies are in the works.)  Big improvement in depression for both anti-depressants but nortriptyline was much better than paroxetine.  [paroxetine CR = Paxil CR; nortriptyline = Pamelor]  Nortriptyline affects both serotonin and norepinephrine in the brain.  Paroxetine affects only serotonin.  This study calls into question the use of SSRIs as first line treatment in PD.  Two other newer drugs that affect both serotonin and norepinephrine are Cymbalta and Effexor.  Paxil was effective for some in the study.  (23:48)

Sleep problems in PD are more common than would be expected from age alone.  50-75% of people with PD have trouble with sleep.  In their current study, sleep was the #1 predictor of quality of life (even more than motor problems).  The most common sleep problem is difficulty staying asleep (74-88% of patients).  Other problems:  poor quality sleep, difficulty falling asleep, muscle movements (PLMS and RLS; up to 15%), sleep apnea (up to 12%), RBD, morning headaches.

RBD (REM behavior disorder) is a particular concern.  PD accounts for 27% of RBD cases.  32% had injured themselves and 64% had assaulted their spouse.  Acting out dreams.  Can be a few vocalizations or something more dramatic.  People are reluctant to talk to MDs about this.  There’s a good treatment for RBD that works most of the time.

Excessive daytime sleepiness (EDS) occurs in up to 51% of PD patients.

Sleep attacks (sudden onset of sleep, usually without much warning) are associated with nearly every dopaminergic medication but especially Mirapex and Requip.  3.8% of PD patients had sudden attacks while driving.  Some still debate whether these attacks are caused by these drugs or EDS.

Sleep disturbances in PD may be related to nocturia (frequent need to urinate at night), pain, dystonia, akinesia, difficulty turning, etc.  Sleep is regulated by adrenergic, serotonergic, cholinergic, and various peptidergic symptoms which are disrupted (variably) in PD.  Depression is a major risk factor.  Dopaminergics can also worsen sleep (produce arousal and suppress REM).  (33:00)

Treatment of sleep disturbances includes:  exercise, sleep hygiene, intermittent use of sleep meds (Lunesta, Ambien, etc).  Some medications may help daytime sleepiness including Provigil, Ritalin (an older stimulant), and sometimes amantadine (Symmetrel).

Sleep hygiene:  regular sleep hours; avoid excess time in bed; regular get-up time regardless of sleep quality; avoid daytime naps (of 2 hours in length; 15 minutes is OK); use bed for sleep or sex; relaxation; physical activity; sunlight in morning; bedroom quality (noise, temperature, humidity); avoid evening stimulants; avoid large evening meals.  If you are worrying, get out of bed.  (36:34)

Two categories of unusual behaviors that sometimes accompany meds given for PD:  psychosis (hallucinations and delusions); impulse control disorders (including gambling, binge eating, buying, hypersexuality).

Psychosis is rare in untreated PD.  Can be caused by all PD meds though psychosis is somewhat more frequent with dopaminergic receptor agonists.  Biggest risk factor for developing psychosis is memory impairment.

Hallucinations (seeing something that isn’t really there) occurs in approximately 30% of PD patients.  Usually these are mild.  The problem is when hallucinations are frightening.

Delusions (belief that isn’t shared by other people in your world) occur in 3-17% of patients.  Can cause major problems and be very disruptive.  Generally later in illness when memory begins to fail.  Typically persecutory (eg, fear of being poisoned, infidelity).  Please bring these up with your MD.

There was just a large study on impulse control behaviors just discussed.  Seem to occur more frequently with Mirapex and Requip but can also occur with Sinemet.  (42:03)

In the face of these problems (psychosis or impulse control disorders), the first thing MDs do is reduce the dopamine medication.  “Motion-emotion conundrum.”  If reducing the parkinson meds doesn’t solve the problem, then MDs look to antipsychotics.  (43:08)  The first antipsychotic given is Seroquel.  If that doesn’t work, then Clozaril is tried.  Clozaril requires a weekly blood sample.  Clozaril is very effective.  (43:42)

In early PD, most develop a little of what could be described as “mild cognitive impairment.”  This is impairment of tasks requiring the frontal lobe of the brain — planning, judgment, and recall memory.  This doesn’t cause major problems.  Dopamine replacement leads to some improvement.  (44:39)

The more difficult thing is the more serious memory impairment that happens later in the disease.  Quite a few people develop this.  This is not Alzheimer’s.  This is much, much slower in development than Alzheimer’s, and generally less severe.  There are trials out there looking at the typical AD drugs (such as Exelon) in PD.  In one study, Exelon had a slightly positive response, and some with PD can take this drug.  It’s worth trying.  There is a question if Namenda will work.

Dealing with cognitive impairment includes:  household safety (and preventing wandering), reminders as to the structure of the house, day care, in-home help.

It’s important to educate yourself about psychiatric issues.  Sometimes you have to educate your physician about psychiatric issues in PD.  (46:39)

Question: Is bipolar a precursor to PD?
Answer:  I don’t think so but on the other hand certainly people with PD can develop bipolar disorder (though this would be unusual).  Bipolar disorder hits people early in life.  (48:00)

Question:  Can you elaborate on Lewy bodies?
Answer:  In Lewy body disease, there is wide distribution of Parkinson’s pathology across the brain.  This is a variant of PD where the cognitive impairment and memory impairment progresses much, much more rapidly than in normal PD.  And the individuals are much more sensitive to the adverse side effects of PD.  It’s a much more rapidly progressive illness than normal PD.  Not much is known about LBD.  It can be quite a trial.  (49:10)

Question:  What were the side effects related to nortriptyline?  (50:06)
Answer:  The newer antidepressants are better tolerated.  Surprisingly, nortriptyline (an older med) was well tolerated.  There was more constipation in the nortriptyline group.  Our lesson from the study:  don’t start with an SSRI.  (51:13)

Question:  When will a cure happen?
Answer:  Someday there will be a cure.  But what do you do now?  We need research on the problems we are having right now.  (51:56)

Question:  Can you comment on the French clozapine study?
Answer:  There have been two well-controlled Clozaril trials showing Clozaril is better than placebo for psychosis.  Weekly blood draws for six months can be a problem for some.  Some of the Seroquel trials did not show that Seroquel was any better than placebo.

Question:  Can we view panic reactions as a behavioral equivalent of a motor tremor?
Answer:  I suppose you could look at them that way.  Sometimes those with anxiety have panic attacks.  I don’t know if it’s the same neurochemically.

Question:  Depression vs. anger.  Can anger be a stimulus?
Answer:  Anger can motivate people to make changes in behavior.  If people are having a lot of anger, it’s usually based on relationships and chronic problems.  Counseling may be helpful in determining cause of anger.  Is the anger a personality change?

Question:  What determines sexual dysfunction?  Compared to what you used to do?  Frequency?
Answer:  These problems are happening in people who are older, some of whom have less interest in sex.  Autonomic dysfunction can contribute.  There are also relationship issues.  If something has dramatically changed compared to the past, then we look to some cause (medication?) for the problem.  (56:09)

Question:  If a person with PD is on bipolar meds, and needs an antidepressant, is there a conflict?  Are they more likely to become manic?  Any connection?
Answer:  This is complicated.  Lithium (a bipolar med) can sometimes not be at all well-tolerated in PD.  Med changes have to be made.  But there are some bipolar meds that those with PD can take.  Depression would be seen as a function of bipolar disorder.  In bipolar disorder, we generally try not to use antidepressants because this can worsen the mania.  But we do use them in conjunction with a mood stabilizer.  (58:10)

Question:  My husband becomes agitated and anxious.
Answer:  Agitation can be many things.  Impulsivity can be a personality change.  Is there a change in impulsivity?

Question:  How effective is Remeron for depression in PD?
Answer:  We have no idea.  Remeron is a new kind of antidepressant.  It works differently than Paxil, Prozac, that class.  Remeron tends to be very helpful with sleep.  It has a lot of antihistaminic and anticholinergic effects so it can make constipation worse.  Each antidepressant needs to be studied individually:  does this drug work in this person?

Question:  Is depression in PD hereditary?  (00:48)
Answer:  We don’t know.  We think that in non-PD depression has a hereditary component (“somewhat more likely” to develop PD).  Many people, however, with no family history develop depression, and many people with a family history of depression who never develop it.  Is there something different about PD and depression compared to PD without depression?  We don’t know but it’s a good question.