WESTBERG had yanked four nerves from where they emerged from his spinal cord
in the neck region. The injury left his left shoulder, arm and hand completely
paralysed. The prognosis for this damage, which is regarded as a particularly
severe form of brachial plexus injury, is not good. The paralysis is considered
incurable and permanent, and the arm withers through lack of use.
But through a medical feat that some experts still have difficulty accepting,
Westberg regained the use of his arm after neurosurgeon Thomas Carlstedt at the
Karolinska Hospital in Stockholm reattached two of the torn nerves to their
original site in the spinal cord. Carlstedt鈥檚 repair job appears to have
provided a channel along which new axons, the projections that carry nerve
messages, could grow from the cell bodies in Westberg鈥檚 spinal cord to the
muscles of his arm. Today, Westberg can lift a kilogram weight, and he has
regained about 40 per cent of normal movement in his arm, which has made the
difference between a lifetime of disability and continuing in his job as a car
mechanic.
His remarkable recovery also challenges the conventional notion that when the
nerve cells of the spinal cord are damaged they die, and are neither repaired or
replaced, but irretrievably lost. Against all the odds, it appears that cells in
Westberg鈥檚 spinal cord have grown new axons, which must be well over a foot long
and extend into two of his major arm muscles.
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Not surprisingly, reaction to this 鈥渕iracle鈥� recovery has been mixed.
Neurophysiologist Clifford Woolf of University College London is cautious. He
says that the results 鈥渟trongly suggest鈥� that new axons have grown from the
spinal cord to the muscle, but he adds that Carlstedt and his colleagues must
successfully repeat the operation in more patients, and ultimately confirm their
finding by showing a direct axonal connection from the spinal cord to the
muscles in a postmortem examination of one of those patients.
Ten tedious years
Surgeon Rolf Birch at London鈥檚 Royal Orthopaedic Hospital, on the other hand,
is a firm believer. He calls the technique 鈥渁 truly significant breakthrough鈥�
which provides the only hope of restoring function in many brachial plexus
injuries. Carlstedt has just completed a one-month stint in London working with
Birch and his colleagues, who want to develop the technique to treat their share
of the 350 British adults who suffer brachial plexus injuries each year, usually
in car, motorbike and water-skiing accidents.
Getting to the point where other neurosurgeons were prepared to take
seriously Carlstedt鈥檚 idea for the brachial plexus repair operation was a long
haul. It took 鈥渢en long, tedious years,鈥� before he had perfected his operation
in animals, he says. That work showed that the cell bodies in the spinal cord
start to die within two weeks of the spinal nerves being damaged. But if the
nerves were reconnected during the first month while the majority of cell bodies
were still alive, new axons would grow to the muscles.
Carlstedt鈥檚 decision to attempt the procedure in humans coincided with
Westberg鈥檚 accident and, mindful of the time factor, he had him under the knife
within weeks. To expose the spinal cord, Carlstedt cut through the bony spinal
column and the thick protective membrane called the dura. Two of the four spinal
nerves which had been damaged in the accident were completely wrenched from the
spinal column and were beyond repair. However, the other two were pulled from
the cord, but not the column, and so were candidates for reconnection.
Spinal nerves fork just outside the spinal cord. One root carries sensory
information to the spinal cord from receptors in the skin, organs and muscles;
the second carries instructions to the muscles about when to contract. Carlstedt
took the second root of each nerve and surgically attached it just beneath the
surface of the cord, in one case using a graft taken from a minor nerve in the
leg as an extension.
Axons grow only 1 millimetre per day, so it took many months for them to grow
from the spinal cord to the muscles of the arm. Nine months after the surgery,
Carlstedt first recorded electrical activity that was characteristic of a
nervous input in the biceps and triceps of Westberg鈥檚 left arm, suggesting that
cell bodies in the spinal cord had sent new axons to the muscles. Shortly after
that, Westberg found that he was regaining the ability to contract those
muscles.
In order to eliminate the possibility that another nerve had somehow
compensated for the damaged ones, Carlstedt injected a local anaesthetic
directly into the intact nerve that was most likely to have taken over some of
the function of the damaged ones. Blocking that nerve hampered the deltoid
muscle on top of Westberg鈥檚 left shoulder, but had no effect on his new-found
ability to contract his biceps and triceps (Lancet, vol 346, p
1323).
Carlstedt admits that, at first, even he found it hard to believe Westberg鈥檚
spectacular recovery despite the fact that his animal studies had strongly
suggested that the surgery would work. In a key experiment, he had performed the
same operation on six monkeys with similar spinal injuries. Three regained the
use of their damaged arms. In postmortem examinations of these animals,
Carlstedt found that a dye injected into the monkeys鈥� biceps before their death
had diffused along axons connecting the muscle to the spinal cord and ended up
in cell bodies within the spinal cord. This proved that cell bodies had sent out
new axons that went all the way to the muscles.
Since Westberg鈥檚 recovery, Carlstedt has restored muscle function to another
patient and is waiting to see what happens to four others who have undergone the
operation. Two more patients have showed no improvement. Carlstedt suspects that
the problem with these patients is that their operations were delayed for more
than 4 months as they were referred to the Karolinska from other hospitals.
Now Carlstedt and Morten Reisling, a neuroscientist at the Karolinska
Hospital, are looking for ways to further improve movement in the arm after the
operation, and to widen the window of time for successful surgery. When axons
outside the spinal cord or the brain are damaged, chemicals called neurotrophic
factors stimulate their regrowth. Earlier this year, neurobiologist Fred Gage at
the Scripps Institute in La Jolla, California, announced that implanting
connective tissue cells that make neurotrophic factors into the brains of mice
also stimulates the growth of new axons. Carlstedt speculates that when the
spinal nerves are reattached they mimic that effect by sucking up neurotrophic
factors from out side and transporting them to the spinal cord. Carlstedt and
Reisling are now testing whether injecting these factors can also help keep cell
bodies alive in the damaged spinal cords of rats.
Carlstedt is confident that his spinal nerve operation can be refined.
Perhaps one day it will even be used to help repair severed spinal cords, the
most devastating of all spinal injuries. After all, the major impediment has
been overcome, he says. 鈥淲e鈥檝e shown that regeneration in the spinal cord, which
had been thought to be impossible, can happen.鈥�