Many options to treat nystagmus, more in development

Baltimore-While once there was little to be done for patients with nystagmus, a series of medications has been discovered over the past 25 years that help many individuals with different forms of the condition, and more options are on the horizon, said David Zee, MD, professor of neurology and ophthalmology, the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore.

"Until about 1980, there were no effective medications that could treat nystagmus with any significant amount of improvement," Dr. Zee said. In the past, many of the drugs used to treat various forms of nystagmus were similar to anticonvulsants or sedatives, with their effect at least partly attributable to the drowsiness they caused, he added.

In 1980, however, investigators discovered that a drug called baclofen (Lioresal, Novartis Pharmaceuticals), used to treat spasticity, could effectively stop periodic alternating nystagmus (PAN).

PAN is caused by instability produced by loss of gamma-aminobutyric acide (GABA)-mediated inhibition from the Purkinje cells of the cerebellar nodulus into the vestibular nuclei, and baclofen provides the missing inhibition, stopping the nystagmus.

Pendular nystagmus

The search for additional therapies led to progress in the treatment of elliptical or pendular nystagmus, which is common in patients with multiple sclerosis and particularly debilitating. Gabapentin (Neurontin, Pfizer), a mild anticonvulsant, was found to cause improvement in about half the patients who received it to relieve symptoms of nystagmus. Dr. Zee said. Gabapentin is used off-label for nystagmus therapy.

At roughly the same time, a medicine called memantine (Namenda, Forest Laboratories Inc.) was found to be effective in some patients for treatment of the same type of nystagmus. "It was not 100% cured and it was not in all patients, but there was significant improvement in a lot of patients," Dr. Zee said.

Memantine was initially available only in Europe; it was recently approved in the United States for treating memory loss in patients with Alzheimer's disease. This made the drug available to physicians who wanted to use it off-label for nystagmus.

The arrival of this drug is another step forward for certain nystagmus patients. "This is really important because with pendular nystagmus the eyes are never still; they are always moving, so there is no time when the eyes are still enough that the visual system can really take in new visual information and analyze it properly," Dr. Zee said.

Yet another promising medication for nystagmus associated with multiple sclerosis is levetiracetam (Keppra, UCB Pharm Inc.), which is FDA approved for the treatment of partial seizures in adults and children 4 years of age and older with epilepsy. Because this drug is mild and has few side effects, it could be an appropriate choice for some patients with nystagmus in off-label use, Dr. Zee said.

Another advance came from German physicians who discovered treatments for downbeat nystagmus called 3,4-diaminopyridine and 4-aminopyridine that are effective in at least half of patients treated with these agents, according to Dr. Zee.

Researchers have also found a new use for a drug formerly used in glaucoma therapy known as acetazolamide (Diamox, Barr).

"This improves some of the symptoms of patients who have a rare condition in which they have episodic imbalance and episodic nystagmus," Dr. Zee said.

Acetazolamide decreases attacks of episodic ataxia type 2 and sometimes decreases gaze-evoked and downbeat nystagmus as well, he added.

No drug tends to be effective in treating all forms of nystagmus because the disorder has many different causes, Dr. Zee said. Also, he said that scientific advances could produce further breakthroughs in the near future.

"We are learning so much from molecular biology about what kinds of chemicals are transported across cell membrane that we can now make some predictions based upon this new knowledge and a careful analysis of the eye movement as to what medicines might work," Dr. Zee said. "We are moving a little bit away from simply empiricism and developing a rational basis for choosing medications."

He added that an engineering approach is used to pinpoint where the oscillations of nystagmus originate in the brain, while physiology and neuropharmacology are enlisted to try to predict what medication might affect the oscillation in various parts of the loop.