SAN DIEGO – A new adverse event may be emerging for dalfampridine – trigeminal neuralgia in multiple sclerosis patients with a preexisting trigeminal injury, or worsening of the condition in those who already have it, according to Dr. Gary Birnbaum, director of the Multiple Sclerosis Treatment and Research Center at the Minneapolis Clinic of Neurology.
Within a month of starting the drug at his clinic, three women with well-controlled trigeminal neuralgia "had very significant increases in the severity of their trigeminal pain," he said.
Dr. Gary Birnbaum
Stopping the drug brought some temporary relief to two, but they soon relapsed and their pain is now "very, very difficult to control," requiring substantially higher pain medication doses than before, he said.
In the third woman, the pain continued despite stopping the drug and no longer responded to pain medication. It was so severe that she contemplated suicide; she eventually had a trigeminal rhizotomy.
They had "very, very severe pain after" starting dalfampridine (Ampyra), "and it didn’t get better" when it was stopped. "That is what’s disquieting about it," Dr. Birnbaum said at the American Academy of Neurology (AAN) annual meeting.
A fourth patient developed trigeminal neuralgia after 18 months on the drug; the side of his face had only been numb previously. He now requires pain medications for the condition. Brain MRIs of all four patients were stable.
"Irreversible injury [appears] to have occurred in our three patients, and perhaps even in the fourth. Dalfampridine needs to be used with caution in multiple sclerosis patients with preexisting trigeminal neuralgia as well as in those with evidence of preexisting trigeminal nerve injuries," Dr. Birnbaum said.
When prescribing the drug, "I have to tell [patients] now that there’s a possibility that their trigeminal neuralgia may get worse, and it may not get better if they stop [the drug]. They have to take that into consideration," he said in an interview.
The four cases are not the first to be reported since the potassium channel blocker was approved for MS in 2010 to improve walking.
Investigators from the Mayo Clinic in Scottsdale, Ariz., reported two cases at AAN’s 2012 annual conference, both within a month of starting the drug and both in patients whose trigeminal neuralgia had been in remission. One patient responded to pain medications, the other needed a rhizotomy.
"As I talk to [physicians] about these data," people come up and say, "I’ve seen the same thing," Dr. Birnbaum said.
Dalfampridine improves action potential conduction in demyelinated axons. Perhaps when sensory nerves – such as the trigeminal – have a preexisting injury, that effect can lead to a type of "metabolic exhaustion" that makes the injury worse.
"Could there be a similar phenomenon with motor nerves? Perhaps one sees an initial improvement in motor function, but in the long term could this perhaps be deleterious? I have no data to support that, but the implication is that [it’s] a possibility," he said.
Dr. Birnbaum is a paid consultant to TEVA, Serono, Genzyme, Questcor, and Biogen Idec. Biogen Idec and Hoffman-LaRoche have both supported his research.