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NEWS FROM THE AAN ANNUAL MEETING: Diaphragm Pacing for ALS Patients How to Identify Best Candidates

Rukovets, Olga

doi: 10.1097/01.NT.0000431663.17135.ea
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Based on retrospective data on pre-operative measures that had been used for 30 implanted diaphragm pacing systems (DPS) in patients with amyotrophic lateral sclerosis, investigators identified three different tests and clinical exams as predictors for who would most benefit from DPS.

What tools can help predict an amyotrophic lateral sclerosis (ALS) patient's response to electrical stimulation of the diaphragm to help with breathing? According to an analysis of data on the NeuRx Diaphragm Pacing System (DPS) — which the FDA approved in 2011 through a humanitarian device exemption — three pre-operative tests and clinical judgment are helpful. The investigators reported their findings at the AAN annual meeting in March.

Robert Baloh, MD, PhD, director of neuromuscular medicine in the department of neurology at Cedars-Sinai, and colleagues, examined retrospective data on pre-operative measures that had been used for 30 implanted DPS devices; the DPS uses surgically implanted electrodes along a patient's diaphragm to send electrical pulses that cause the diaphragm to contract.

According to their data, Dr. Baloh said, clinical judgment and results from three pre-operative tests — forced vital capacity (FVC), radiographic SNIFF testing, and a bilateral phrenic nerve conductive study — can help predict the most (and least) eligible patients for the DPS.

FVC is the most commonly used criterion here and in many ALS centers for observing function of the diaphragm and capacity to breathe, Dr. Baloh said. The FDA criteria state that FVC cannot be less than 45 percent of predicted normal values. The SNIFF test, which looks at the movement of the diaphragm fluoroscopically while a person sniffs, to see how well the diaphragm is moving — helps neurologists determine if both sides of the diaphragm moving at all. If so, are they moving normally or paradoxically, that is, is the diaphragm moving in the wrong direction, indicating that it's essentially paralyzed, Dr. Baloh explained.

The researchers had compared each patient's pre-operative test results with intra-operative findings during direct diaphragm stimulation. “We also looked at the patients overall clinical picture after placement of the device to come to our overall conclusions,” Dr. Baloh said.

The parameter that best matched with successful diaphragm stimulation was the SNIFF test, followed by the phrenic nerve to diaphragm compound muscle action potential (CMAP), and then the FVC, the study authors reported. Moreover, they wrote, applying the three parameters along with clinical assessment of the patient can support successful intra-operative diaphragm stimulation. “We are looking at either improving these three parameters or finding new criteria to follow,” they concluded.

The overriding question, Dr. Baloh told Neurology Today, is how effective this device is for maintaining function of the diaphragm and improving quality of life for these patients. “That, of course, is not really what we were addressing here, but the work described here might help us to select the right patients to implant,” he told Neurology Today.

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In a telephone interview with Neurology Today, Kirsten Gruis, MD, an associate professor of neurology at Upstate Medical Center in Syracuse, NY, said that this abstract comes from a group of people with a substantial amount of experience with DPS, and so “their ability to report the clinical findings of the electrophysiology of the diaphragm and the pulmonary function tests before and after [implantation] adds further knowledge about what this device may be able to do or not be able to do for ALS patients going forward.”

These findings, she said, tell us that the “current information we have about diaphragm function before DPS implantation is reasonable to proceed with,” which is reassuring, but there are still many unanswered questions that warrant further investigation.

Dr. Gruis is a principal investigator of a randomized controlled trial evaluating DPS efficacy. Right now, she said, we have information about proof-of-concept — “that the device can be successfully implanted at a time when ALS patients have breathing muscle weakness and preliminary data suggest that it may be of benefit in improving diaphragm muscle function. We're taking the next step forward [with our trial, by] looking at the effectiveness of diaphragm pacing for survival and for diaphragm muscle function.”

Robert G. Miller, MD, director of the Forbes Norris MDA/ALS Research Clinic at California Pacific Medical Center in San Francisco, who has been involved with the FDA approval trials and post-approval trials for the DPS, said that the results were in line with what they have been seeing firsthand in their own clinic in San Francisco.

Dr. Miller said that he would even go one step further than the authors did, and, based on the work at his own center, conclude that “selecting patients as early as possible will ensure that the best response will be found intraoperatively. The most sensitive of the breathing tests is the MIP (maximum inspiratory pressure) and a very large number of patients, when they are first seen in the ALS center, will have a modest abnormality of the MIP, while other breathing tests are normal. That is the perfect time to educate the patients about both diaphragm pacing and also about non-invasive ventilation,” he told Neurology Today.

Dr. Miller and colleagues published a paper comparing MIP to FVC measures before noninvasive ventilation in the journal Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration in 2007 (

Research shows that the people who use non-invasive ventilation (NIV) live longer, have a higher quality of life, and lose breathing function more slowly than those who don't opt for NIV, he said. The data presented to the FDA, Dr. Miller continued, suggest that this may be true for the DPS also, since “there seemed to be a slowing in the rate of decline of pulmonary function in people who used the diaphragm pacer, and also nine months longer life on average for that group of patients.”

Currently, based on both their own experience and these abstract data, “we are presenting patients with these two options — diaphragm pacing and noninvasive ventilation — as soon as the MIP is at -60cm H20, [which is] the earliest indicator that the diaphragm is starting to get weak,” he said, and achieving excellent results.



Dr. Miller is the principal investigator on the REGISTRY trial, which is the post-approval study (PAS) based on the FDA approval of the DPS. In that study, he said, “we are trying to gather data and experience on people with DPS in order to be able to look more convincingly at what protocols are best for screening patients for this procedure, which patients are benefiting the most from the treatment, and the degree of benefit.”

We'd like to know, he added, if the increased survival time they found in the initial study will hold up for the next group of patients. “At the end of that study and the PAS study, we will have a lot more information about the value of diaphragm pacing — who is most likely to benefit and who is least likely to benefit — in order to guide our clinical use of this in the future,” Dr. Miller said.

For more commentary on the study, watch the accompanying video with Neurology Today Editor-in-Chief Steven P. Ringel and Associate Editor Robert Holloway, MD.



LISTEN UP: In a podcast, Robert Baloh, MD, director of neuromuscular medicine in the department of neurology at Cedars-Sinai, talked to Neurology Today about the currently available data on the Diaphragm Pacing System in ALS patients and what research still needs to be done:



TUNE IN: In a study presented at the AAN annual meeting last March, researchers reported that three pre-operative tests combined with clinical judgment are helpful in predicting diaphragm excitability in amyotrophic lateral sclerosis (ALS) patients. In a video interview, Neurology Today's Editor-in-Chief Steven P. Ringel, MD, and Associate Editor Robert Holloway, MD, discuss the implications of these findings for ALS experts and patients:



A ‘BEST PAPER’ PICK: Neurology Today Editor-in-Chief Steven P. Ringel, MD, and Associate Editor Robert Holloway, MD, selected this as one of the noteworthy papers highlighted by the AAN Science Committee for presentation at the AAN annual meeting.

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•. AAN meeting abstract (2013): Selection criteria of diaphragm pacemaker implantation in ALS patients:
    •. FDA approval of NeuRx Diaphragm Pacing System (DPS):
      •. Neurology Today archive on DPS:
        ©2013 American Academy of Neurology