BOB
Drug helps spinal cord injury patients
TORONTO, Sep 28 (Reuters) -- Encouraging results have been observed
following a
3-month trial of the drug 4-aminopyridine, a potassium channel blocker,
in patients with
long-standing spinal cord injury.
It is among the few beneficial effects of drug therapy in long-standing
spinal cord injured
patients reported, Dr. Jack Segal of the Veteran's Affairs Medical
Center, Long Beach,
California, said at the joint meeting of the American College of
Clinical Pharmacology, the
Canadian Society of Clinical Pharmacology, and the Royal College of
Physicians and Surgeons
of Canada.
Segal reported that on average, patients regained at least 1 to 1.5
neurological levels of function
after 3 months of treatment with 30 milligram per day doses of
4-aminopyridine. Control
patients on low-doses (6 mg/day) of the drug showed no significant
improvement in any of the
primary or secondary outcomes over the same study period, he added.
Following injury to the spinal cord, many of the nerves at the site of
the injury lose their
protective, myelin sheath. This interferes with the conduction of nerve
impulses across the
damaged areas. The drug 4-aminopyridine is thought to be capable of
helping impulses cross
demylinated nerves, thus restoring some function.
The study involved 21 patients, all with spinal cord injuries of at
least 2 or more years duration.
Of these, 14 were quadriplegic, with paralysis affecting all four limbs,
and seven were
paraplegic, with paralysis affecting the lower limbs.
Sixteen patients received full-dose (30 mg/day) 4-aminopyridine, while
six patients received 6
mg/day 4-aminopyridine and served as controls. The investigators looked
at the patients'
composite motor scores as well as tests of sensation. Both measures
increased significantly
after 3 months in the 30 mg/day group relative to baseline.
"This improvement translated not only into scores that we could
quantitate, but there were
significant changes in patients' ability to carry out activities of
daily living," Segal said. For
example, some patients became able to independently transfer from
wheelchair to bed. Others
reported enhanced sexual function and some patients recovered bowel and
bladder function,
Segal noted.
A significant improvement was also seen in spasticity, increased muscle
tone and uncontrolled
spasms, which is a common problem in spinal cord-injured patients.
Spasticity frequently
manifests as painful muscle spasm, especially at night. "As a result,
some patients who hadn't
had a full night's sleep for years reported significant improvement in
sleep," Segal said.
Equally, if not more importantly, he said, 4-aminopyridine improved
pulmonary function by
30% to 40%. Since pulmonary infections are a frequent cause of morbidity
and death in the
spinal cord patient, the ability of 4-aminopyridine to strengthen
respiratory muscles and the
diaphragm, and to improve the patient's ability to breathe, cough and
clear secretions could
directly translate into a reduced susceptibility to pulmonary
infections, Segal said.
He warned that 4-aminopyridine is contraindicated in acute spinal cord
injury because it carries
an increased risk of seizure in the acute injury setting. However, Segal
said that the drug can be
considered in patients whose injuries are a year or more in duration.
Taken with meals, the drug
is also reasonably well tolerated, he added, with no serious adverse
events observed in the
study group of patients over the 3-month trial.
Segal also noted that longer-term treatment with 4-aminopyridine, which
many of the patients in
this initial study have remained on, may continue to enhance sensory and
motor function. In his
experience, patients who continue with treatment go through interludes
where they suddenly
gain additional, noticeable improvement in function, which are followed
by plateaus. This
phenomenon suggests that patients with long-standing spinal cord
injuries may continue to
improve with longer term use of 4-aminopyridine, he commented.