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9.20.2016

Ongoing Study Improves Predictions of Which Chiari Malformation Patients Will Benefit from Surgery

A research team led by Noam Alperin, Ph.D., professor of radiology and biomedical engineering, and Director of the Physiologic Imaging and Modeling Lab, has continued to refine the means of determining which patients with a neurological disorder known as Chiari Malformation Type I (CMI) will benefit from surgery.

CMI is characterized by tonsillar herniation, a condition in which a part of the brain, the cerebellar tonsils, has descended out of the skull into the spinal area. The resulting crowding causes compression of parts of the brain and spinal cord and disrupts the normal cerebrospinal fluid physiology. Symptoms include severe headaches, gait problems, numbness in the extremities and motor weakness.

“The traditional determination of a diagnosis of CMI was a descent by the cerebellar tonsils of greater than 5 millimeters,” said Alperin. “The problem was that some patients who fit that definition have no symptoms, and some patients with a small descent have severe symptoms. Historically, for every 10 patients diagnosed with CMI who have corrective surgery, which involves removing a portion of the skull bone and/or brain tissue, three have had poor outcomes. Clearly we needed a more comprehensive way of identifying appropriate surgical candidates.”

Two years ago, Alperin’s team, collaborating with investigators from the University of Munich and the University of Pittsburgh, identified a group of complementing morphologic and physiologic measurements that better characterized CMI. The next step was to determine surgical outcomes based on the use of those measurements.

The researchers recruited 15 subjects in whom CMI was newly diagnosed and who underwent MRI measurements before and three months after surgery. More than 20 morphological and physiological parameters were used to assess quantitatively which were the best indicators of a positive outcome.

“Tested physiological measures were stronger predictors of outcome than the morphological measures in the study subjects,” said Alperin. “Maximal cord displacement and intracranial volume change during the cardiac cycle together with a measure that reflects the cerebral venous drainage pathway emerged as likely predictors of decompression outcome.”

An article describing the investigators’ latest findings, “Magnetic Resonance Imaging-based Measures Predictive of Short-Term Surgical Outcome in Patients with Chiari Malformation Type I: A Pilot Study,” was recently published in the Journal of Neurosurgery–Spine.

“This study is an important milestone,” said Alperin. “Our previous papers didn’t have surgical outcomes correlated with our parameters. Now we know who benefitted and who did not, even though all were classified as having Chiari based on our previous work. It’s the first time we have had quantitative evidence for determining the best surgical candidates. Even though it’s only a small number of patients, it’s still hard-to-ignore data. This is a valuable new insight.”

Alperin’s next step will be to apply for a continuation of the NIH grant in order to recruit several additional centers and expand the scale of study.

“We only used one surgical technique at UM; with a multi-center study we will be able to assess the efficacy of other surgical techniques as well,” said Alperin.

Miller School researchers participating in this phase of the study were two medical students, James Ryan Loftus and Carlos J. Oliu, Ahmet Bagci, Ph.D., senior research associate in radiology, Sang H. Lee, M.S., systems analyst in radiology, Ashish H. Shah, M.D., a resident in neurosurgical surgery, and Barth A. Green, M.D., professor of neurological surgery and Executive Dean for Global Health and Community Service.

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