At some point, a
shoe falls in a person's brain, molecularly speaking. Something shifts in
a neural network and a still hand holding a coffee cup starts to shake.
"After I got my tremor" becomes someone's new way of marking
time.
Neurologist Allen Mandir, M.D., longs to know what sparks
this shift. But a key step in doing that-linking small changes in the
brain with their effects on movement-hasn't yet happened. For one thing,
no one has a precise-enough handle on tremors. "Many think a tremor is a
tremor is a tremor," Mandir says, "yet tremors vary, not only by specific
disease but within the course of it."
Mandir puts a monitored finger through the paces.
Recently, Mandir and a team
including psychiatrist Laura Marsh, M.D., improved an existing
method to quantify tremors, a tactic that could insure earlier and better
diagnosis of Parkinson's disease (PD) and other motor ills. A full-blown
parkinsonian shake --the large-amplitude, 5-cycle-per-second variety-- is
obvious, he says. "But now we can detect early tremor so subtle even the
patient doesn't know about it." Before long, the technique should bring
precision to marking where patients stand in the course of motor disease.
You can also follow treatment progress, he says.
Basically, Mandir
singles out a finger and affixes three accelerometers --devices similar to
air-- bag sensors in automobiles. Software he created transforms finger
data into a printout of tremor depth and frequency. With it, he can
distinguish cerebellar, parkinsonian and essential/physiological tremors
or some unexpected mixes: He recently found the constant hand movement of
many Parkinson's disease patients tinged with aspects of benign essential
tremor.
Also, because drug treatments for motor disease
prompt "pretty strong" placebo effects, quantifying tremor can eliminate
that patient bias, he says.
But tremor's not Mandir's sole focus.
He's also deconstructing the akinesia--difficulty
initiating movement-- and slowness of movement, orbradykinesia that mark motor disease. By focusing on
basic movements wired in the primate brain --in this case, a simple
back-and-forthing of the hand between two marks on a table-- he gets a
normal baseline reading to compare with motor disease
patients.
With electromyelography, the team records electrical
activity in target muscles. Typically, three phases of firing appear: a
burst when movement begins, when it's carried out and when muscles put on
the brakes. "PD patients, however, don't shut off like they should. They
overshoot; they undershoot. The crisp pattern is gone. You can see
bradykinesia's slow movement for example, or akinesia's simultaneous
firing of opposing muscles."
One surprising find --that PD
patients move more normally when someone says "go"-- may spark a novel way
to improve ability. "The 'go' signal may help evade bradykinesia and
akinesia," says Mandir. He's confirmed the effect in monkeys and is
testing a patient-carried device that gives audible cues.
Mandir
has quantified things so well at the muscle level he's able to spot
corresponding events in the brain. With functional MRI, he has matched
brain activity to the three phases of his movement task. Most important,
he can map the bursts' origin in the brain. The supplementary motor area,
for example, appears linked to readying and initiating movement. "In PD
patients, that area atypically fires at a low rate, doesn't build and
screws up the timing of movement."
Everyone knows the substantia
nigra as the seat of Parkinson's, he adds, but proving other areas are
involved has great importance for therapy. "We're seeing PD's effects
throughout the brain. My hope is that the disease's pathology is minor;
correct it and there'll be a massive righting of the brain." For more information, call
410.614.1216.
