Sunday, September 30, 2012

Bicycle Built for Two

Bicycle bicycle bicycle
I want to ride my bicycle bicycle bicycle

I want to ride my bicycle
I want to ride my bike
I want to ride my bicycle
I want to ride it where I like

-Queen, “Bicycle Race”

It won't be a stylish marriage --
I can't afford a carriage,
But you'd look sweet upon the seat
Of a bicycle built for two.

-Harry Dacre, "Daisy Bell (Bicycle Built for Two)"

~ ~ ~

In the world of hipsters and wannabes, wedding blogs and Pinterest, anyone who is between the ages of 20 and 40, or knows anyone between the ages of 20 and 40, will have already been familiar with the adorable image of a tandem bicycle on a wedding invitation (if you haven’t yet, don’t worry – it’s coming.)  However apt the image of a tandem bicycle might be for a new marriage or young love, in the unexpected setting of Parkinson’s disease, it makes an even more fitting, touching and literal symbol of not only love and devotion but even cutting edge medical promise, as well.

~ ~ ~

Parkinson’s Disease is a devastating neurological condition in which the afflicted slowly lose control over the movements of their body.  Slowness, tremors, deterioration of speaking ability and balance are some of the major manifestations of this disorder that affects an estimated 1 million Americans, and for which there is no cure.  In addition to problems with movement, people with PD also commonly suffer from depression, dementia, sexual difficulties and sleep disturbances.

PD is a progressive, degenerative nerve disorder that affects the neurons in the brain that control movement. The main neurons affected are located in the substantia nigra of the basal ganglia, which serve as the coordination center for signals coming from the cortex of the brain to the spinal cord in order to move muscles on command.  Their deterioration causes a deficiency of dopamine, a key chemical for proper brain function and the main neurotransmitter that they produce.  This is where the bicycles come in.

In the spring of 2010, Dr. Bastiaan Bloem of the Radboud University Nijmegen Medical Center in the Netherlands was visited by a patient with advanced Parkinson’s.  This man had been afflicted with the condition for ten years, and he had been left nearly unable to walk at all, with a severe balance deficit, feet that repeatedly froze on the floor and a tremor that would cause him to fall after just a few shuffling steps.

This patient told his doctor that he could, however, still ride his bike perfectly – and was determined to prove it.  So doctor and patient went out to the parking lot, and with the help of a nurse to get him on the bike and shoved off, the patient rode off in perfect control, making a U-turn at the end of the parking lot and pedaling smoothly back, all Parkinson’s symptoms vanished.  The moment he brought the bike to a halt and stepped off, he froze immediately, unable to move his legs in a single step.  The episode was filmed and photographed, and the images were published in the April 1st, 2010 issue of the New England Journal of Medicine.

Dr. Bloem – wheels turning, as it were – then asked 20 of his other patients severely affected by Parkinson’s disease if they could ride a bike.  It turned out that they all could. 

One explanation for the finding, according to Dr. Bloem, could be that bicycling uses a different part of the brain than walking – and that this part might not be so severely affected by Parkinson’s disease.  It could be, perhaps, that bicycling doesn’t require very much input from the part of the brain that’s diseased in Parkinson’s patients, the basal ganglia.  It’s the basal ganglia that processes signals for voluntary movements, and its impairment is the reason Parkinson’s patients freeze – the part of the brain that tells them what to do next isn’t functioning.  It’s certainly possible that one of the reasons the Dutch patient wasn’t showing any sign of Parkinson’s while riding a bike is that riding a bike doesn’t require a lot of signal processing in the basal ganglia.  Nurses helped the patient onto the bike and got him going, but once he was going, he could keep doing the same thing without much thought about motor strategies.  (Gives new significance to the old adage, “like riding a bike.”)

Another theory regarding the reason for this phenomenon is that it could be that the rhythmic pressure of the pedals on patients’ feet cues the nervous system to allow a cycling movement.  He suggests that the rotary motion of the pedals may provide an external pacing cue that keeps the Parkinson’s patients on track.  Given appropriate visual or emotional cues, people with Parkinson’s can dance, walk without freezing and perform complex movements for a few minutes at a time.  For example, there are many stories about patients with PD being caught in a building on fire and finding themselves able to run down stairs and escape safely, only to have symptoms return as soon as they got outside.  But this kinesia paradox, as it is known, does not last long, and is entirely different from being able to ride a bike flawlessly for miles at a time.  Until now, it was not known that patients with Parkinson’s could ride bikes.

In fact, the "bicycle sign" might help clinicians differentiate between the Parkinson’s disease and Parkinsonism of other disorders.  Patients with atypical Parkinsonism lose their ability to cycle during the early phase of the illness, while patients with Parkinson's disease continue to ride well.  This has important treatment implications because atypical Parkinsonism disorders can often look very similar to Parkinson's disease, but respond differently to therapy.  There is a legitimate question of whether or not the bicycle sign is universally applicable, given environmental and cultural differences between patients (Dr. Bloem and his patients reside in the the Netherlands, where absolutely everyone rides a bike.) 

~ ~ ~

While there are a number of useful medications that help ease Parkinson’s disease symptoms for a few hours, advancements in significant relief have eluded Parkinson’s researchers.  In a surprising and somewhat whimsical discovery, new evidence suggests that tandem cycling may bring a longer relief from the disease’s symptoms, with improvements lasting for weeks at a time.

The serendipitous discovery was made in 2003 when neuroscientist Jay Alberts, then a Parkinson’s disease researcher at Emory University in Atlanta, rode a tandem bike across the state of Iowa with his friend Cathy Frazier, a Parkinson’s patient.  The two were riding the staewide bicycle tour to raise awareness of the neurodegenerative disease, but they also found, much to both of their surprise, that her tremors disappeared after about an hour of riding.  She told him that she felt great while riding and that it was as if she didn’t have the disease.  They also noticed that her handwriting improved.  Patients with Parkinson’s often develop micrographia, meaning that their handwriting becomes small and illegible.  Alberts’ friend Cathy had noticed the progressive shrinking and illegibility of her handwriting as her PD progressed, but during this bike tour, she wrote on a birthday card with beautiful, large, legible letters.  It made Alberts take note.

Alberts wondered if this mysterious side effect of the tandem bike ride held an intriguing medical possibility: the improved motor control in the arms and hands even though only the legs were exercising seemed to suggest that there was some change taking place in the central nervous system that improved global motor function, perhaps by triggering the release of biochemical messengers.

Now a researcher at the Cleveland Clinic, Jay Alberts has conducted several studies with Parkinson’s patients inspired by these discoveries and his passion for biking.  Many patients are able to lower their medication dosages and regain motion in extremities.  Other patients have regained their sense of smell from bike riding, which is commonly lost in PD and often one of the first symptoms that patients notice before being diagnosed.

Dr. Alberts had volunteers with Parkinson’s ride a solo stationary bicycle at his or her own pace.  Most chose a pedaling cadence of around 60 revolutions per minute, a relatively non-strenuous level of exertion.  He then placed them on the back seat of a tandem bike that had been modified to ensure that the back rider would have to actively pedal; he or she could not just passively let the pedals turn.  On the tandem, the rider in front had been instructed to pedal at a cadence of about 90 RPM and with higher force output or wattage than the patients had produced on their own.  The result was that the riders in back had to pedal harder and faster than was comfortable for them.

Tandem bike riding has turned out to be beneficial therapy for patients, but Alberts determined it was because the exercise was forced.  The challenge of pedaling much faster than normal activates the part of the brain that controls body movements and releases dopamine, which is what improves symptoms in Parkinson's patients.  According to Alberts, the medications often given for symptom improvement in PD activate certain areas of the brain or increase the blood flow there, and an almost identical pattern of activation is seen in the brains of patients who have done forced exercise.

This is an exciting finding because it contrasts with some earlier results involving voluntary exercise and Parkinson’s patients.  In those experiments, the activity was helpful, but often in a limited, localized way.  Weight training, for instance, led to stronger muscles, and slow walking increased walking speed and endurance.  But such regimens typically did not improve Parkinson’s patients’ overall motor control.

The forced pedaling regimen, on the other hand, did lead to better full-body movement control, which prompted Dr. Alberts to conclude that the exercise must be affecting the riders’ brains as well as their muscles.  His theory that was substantiated when he used functional M.R.I. machines to see inside his volunteers’ skulls.  The scans showed that, compared with Parkinson’s patients who hadn’t ridden, the tandem cyclists’ brains were more active.

Dr. Alberts suspects that in Parkinson’s patients, the answer may be simple mathematics. More pedal strokes per minute cause more muscle contractions than fewer pedal strokes, which, in consequence, generate more nervous-system messages to the brain. There, he thinks, biochemical reactions occur in response to the messages, and the more messages, the greater the response.

This raises fascinating questions not only about whether exercise can help to combat the disease but also whether intense, essentially forced workouts affect brains differently than gentler activity does, even in those of us who are healthy.  In lab animals, forced and voluntary exercise can lead to different outcomes.  Mice and rats generally enjoy running, and they will voluntarily hop aboard and run on a wheel placed in their cages.  But if an animal is placed on a treadmill and the speed controlled so that it must keep pace, often with help from a finger prod or electrical shock, the activity becomes forced.

Interestingly, the effects in animals, especially on their brains, are typically more beneficial after forced exercise.  In one study from 2008, rats forced to run wound up with significantly more new brain cells after eight weeks than those who ran when they chose, even though the latter animals ran faster.  And in another experiment, mice that were required to exercise on treadmills subsequently performed better on cognitive tests than those given access to running wheels.

A small eight-week study was launched to gauge the effects of forced exercise in which the patients underwent hour-long sessions of forced riding, pedaling at 80-90 RPM.  And the results were impressive: there was a 35% improvement in motor functioning, significant lessening of tremors and better body control for the patients who did the forced exercise compared with those exercisers who pedaled a stationary bike at their own pace, and the improvement lasted for four weeks after the cycling sessions ended.

Whether forced exercise would similarly affect healthy brains is unknown at this point, he says, as is the question of whether riding on the back of a tandem behind a stronger cyclist is the only qualifying exercise.  It seems likely that intense exercise of any kind should produce comparable brain reactions.  There is even some data showing that people who exercise intensely have a lower risk of developing Parkinson’s and other neurological diseases. 

In addition to motor difficulties, individuals with Parkinson's disease often experience cognitive declines.  And although pharmacologic therapies are helpful in treating motor deficits in PD, they do not appear to be effective for cognitive complications.  While acute bouts of moderate aerobic exercise have been shown to improve cognitive function in healthy adults, individuals with PD often have difficulty with exercise, for obvious reasons.  Another recent study looked the effects of passive leg cycling on executive function in PD, which was assessed with two different tests before and after the cycling.  Volunteers showed significant improvements on the test after exercising, and the difference between times to complete the two exams significantly decreased from pre- and post-cycling times.  It is thought that the improved executive function after passive cycling may be the result of increases in cerebral blood flow, which correlates with theories regarding post-cycling motor function improvement as well, suggesting multiple benefits from forced exercise in patients with PD. 

Regardless, bicycling offers patients an opportunity to be symptom-free while they are riding, to look and feel normal, and to get some real cardiovascular exercise even when their disease is so far advanced that they cannot walk.  The humble tandem bike was one of the Top 10 Medical Innovations for 2010 at Cleveland Clinic.  Remember how awesome that is the next time a bride-to-be tells you how totally adorable she thinks it would be to exit her reception on one.  It could add just the perfect element of kitsch to her perfectly color-coordinated DIY wedding.  But it could also hold the key to someday saving lives.


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