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News from the AAN Annual Meeting: A Report Card on Neurological Conditions

Friedman, Roberta Phd

doi: 10.1097/01.NT.0000398694.55572.72


Progress not imaginable two decades ago now marks many fields of neurology practice — multiple sclerosis (MS), stroke and epilepsy, as well as emergent technologies in Parkinson disease and Alzheimer disease. This was the bright picture offered by outgoing AAN President Robert Griggs, MD, in his presidential plenary lecture here at the 2011 AAN annual meeting in Honolulu.

Dr. Griggs, professor of medicine, neurology, pathology, pediatrics and laboratory medicine at the University of Rochester and its Center for Human Experimental Therapeutics, pointed out that the brain sciences currently bow only to cancer as the most funded line of research, and that should make it easier to recruit the best and the brightest. In the last decade the US has doubled its percentage of graduating MDs entering neurology, with 50 percent of MD-PhDs now at work in the neurosciences.

Dr. Griggs noted that neurologists “are brilliant” in bringing advances from the lab into preclinical testing. But to move beyond academic science into clinical trials and take on health disparities — “for this, we are not quite as good.”

When it comes to quality measures, Dr. Griggs said, “this is the less familiar: how to change patient and physician behavior; to affect health policy, promote global initiatives — we haven't given enough thought to this alien territory where other specialties are ahead; our funders at NINDS haven't yet championed this.

“We are hypnotized by spectacular neuroscience; we need to be more focused on changing behaviors in that teachable moment,” Dr. Griggs said, referring to the chance in patient visits to share the so-called “life's simple seven” habits of lifestyle such as not smoking, finding and treating high blood pressure, eating food low in cholesterol and saturated fats, pursuing an active lifestyle, and maintaining a healthy weight, along with regular medical exams. He noted that “199 of 200 people are not doing what we know will prevent stroke.”

Brought into Dr. Grigg's presentation by video, Petra Kaufmann, MD, NINDS associate director for clinical research, said: “Neurologists need to design trials that matter and are not too burdensome.”

NINDS has created a new clinical research network to improve efficiency, Dr. Kaufmann said. For example, clinical trials now use one institutional review board (ethics committee) for all sites, getting studies up and running quickly. NINDS Director Story Landis, PhD, noted, also by video, that robust early trials are needed before taking drug candidates into phase 3 trials.

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Dr. Griggs enlisted colleagues to give additional video “report cards” summarizing the state of the art for five diseases that neurologists often encounter.. Roger Albin, MD, professor of neurology and co-director of the movement disorders clinic at the University of Michigan Health System in Ann Arbor, said that the motor aspects of Parkinson disease respond to the mainstay strategy of replacing missing dopamine, but “now that we have changed the natural history of the disease,” other features are becoming more challenging. Neurologists need to focus on treating non-motor symptoms, as well, he said.

Dr. Albin noted that deep brain stimulation for select patients is very effective but neurologists need to balance that with the risks of surgery and possible cognitive or behavioral effects.

With new insights allowed by optical genetic techniques to peer into the working brain, pioneered by and described here at the meeting by Karl Deisseroth, MD, PhD, of Stanford University, “we have potential for a real physiological understanding of Parkinson disease, and that will allow us to design therapies much more rationally,” Dr. Albin said.

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Speaking about epilepsy, Jacqueline French MD, professor of neurology and director of translational research and clinical trials at the Comprehensive Epilepsy Center at New York University, said that a medicine chest of 17 antiepilepsy drugs allows neurologists “to render two thirds of our patients seizure free” and surgery for targeted patients can be effective, as well. Adjunct approaches, such as vagus nerve or deep brain stimulation will improve the quality of life for many, she noted. Dr. French serves on the editorial advisory board for Neurology Today.

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David S. Knopman, MD, professor of neurology at Mayo Clinic in Rochester, MN, spoke about hope for those confronting Alzheimer disease. “I prescribe,” said Dr. Knopman, “but I point out that this will only relieve symptoms for a short time, and that there is no prevention.” But he said, “there are cardiovascular risk factors that if you treat for in midlife, almost certainly this will have benefit later.”

“We now recognize amyloid accumulation begins decades before people become symptomatic,” Dr. Knopman said. “Reduction of the amyloid in midlife is critical.”

Dr. Knopman added: “I fully believe we are on the verge of identifying targets” for new treatments such as therapies aimed at tau.

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Ralph Sacco MD, chair of neurology at the Miller School of Medicine at the University of Miami, and president of the American Heart Association, the first neurologist to serve in that position, pointed out that nearly 80 percent of potential stroke patients live within 60 minutes of a primary stroke center. He noted that telehealth improves access for others, in which neurologists can coordinate teams to address acute stroke with IV tPA [tissue plasminogen activator]; given within 4.5 hours of a stroke, this is effective. Aspirin within the first 48 hours is also a proven stroke aid, Dr. Sacco said.



Rare diseases remain a challenge, and hope must be provided for families that their efforts matter, Dr. Griggs said, showing a video clip of a family with Batten disease and interviews with a former trainee, Erika Augustine, MD, at the University of Rochester, who is starting to enroll for a clinical trial in the disease.

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For MS, “the field has seen really exciting changes over the last 15 years,” said Anne Cross, MD, professor of neurology at Washington University School of Medicine, in her video report. “We can stop the disease in its tracks for many patients.”

For those who don't respond to the front line drugs, there are newer ones that now can be effective, such as natalizumab, Dr. Cross continued. She cited the recent approval of an orally active drug, fingolimod, which performed better in a head-to-head trial with interferon beta 1A (Avonex) and referred to other orally active drugs and monoclonals. One issue patients have to consider is that some of the stronger, longer acting immunosuppressants could increase the risk for cancer or autoimmune disease, Dr. Cross noted.

Commenting on Dr. Grigg's progress report, Robert Lisak, MD, chair of neurology at Wayne State University School of Medicine in Detroit, said: “For those of us who have been in the field as long as Berch (Griggs) and I have, a talk on therapy in neurology back then would have been a very short talk.”

“Laying out the process of how treatments have come about, along with the challenges, should have been instructive for those in the audience who have not been involved in translational medicine,” he said.

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In a separate presentation during the presidential plenary session focused on his decades of work in MS, Stephen Hauser, MD, professor and chair of neurology at the University of California-San Francisco, agreed that the drugs lined up in the MS pipeline are not only giving hope but are also already “providing unique windows into the underlying biology of the disease.”

Dr. Hauser noted that the key lesion in MS is “vesiculated myelin and always with a macrophage in the vicinity.” Prior models did not truly replicate the human disease, Dr. Hauser asserted. “Clearly B cells are central players in development of focal lesions in MS.”

“We knew for more than 30 years that the HLA gene is involved,” said Dr. Hauser. “After a long fallow period, the second phase of the human genome project allowed many more genes to be linked to MS, with 57 gene variants now identified. All have small effects on MS risk as compared to HLA,” Dr. Hauser noted, “two are involved with vitamin D synthesis or degradation and most of the others are immune related.”

“We are going to have to make sense of the 80 to 1100 mutated genes that we all seem to tolerate in our genome,” Dr Hauser said. Analysis of a thousand people with primary progressive MS has turned up the same variations as those with relapsing MS.

Dr. Hauser called direct to consumer gene testing “problematic yet people want their genetic information now and the genie is out of the bag. The cost is only getting cheaper, it may soon be a thousand dollar genome, but,” he said, “as a number of observers have noted, it is still a million dollar analysis.”

Commenting on Dr. Hauser's lecture, Robert Lisak, MD, chair of neurology at Wayne State University School of Medicine in Detroit, said: “Stephen (Hauser) was perfect in describing how they determined that B cells or their products were involved in pathogenesis, using animal models and human data, to get suggestions of what might be an effective approach, in this case, depleting B cells. And then you take the results from the treatment trial to go back to the lab and learn more.”

©2011 American Academy of Neurology