Functional MRI reveals new findings in brains of diabetic patients

Researchers in the U.K. have used functional MR imaging to show that patients with diabetic peripheral neuropathy (DPN) respond differently to heat and pain stimulation compared with diabetic patients without peripheral neuropathy.

DPN affects around 40% of diabetic patients and has significant associated morbidity and mortality. Both hyper- and hyposensitivity to pain are prominent features, as is disability resulting from limb amputation. But the pathogenesis of DPN remains poorly understood and there are no effective treatments.

DPN is widely thought of as a disease of the peripheral nerves, and much research has been done on abnormalities in peripheral nerve physiology, according to Dr. Iain Wilkinson and his colleagues in the academic radiology department of the University of Sheffield. MR studies have highlighted central nervous system involvement, showing lower spinal cord volumes and proton-spectroscopic thalamic abnormalities in patients with DPN. An understanding of CNS involvement may change the emphasis of treatment development, they noted in a traditional poster at the ISMRM-ESMRMB meeting in Berlin.

The Sheffield team used BOLD functional MRI to monitor the neuroanatomical correlates to heat-pain stimuli in 12 men with diabetes (mean age 54 ± 12 years). A detailed neurological evaluation that included neurophysiological tests was performed to diagnose and stage the severity of DPN. Only four subjects did not have neuropathy. Of those with DPN, four had painful DPN and four had painless DPN. The cohort was later expanded to include six patients in each of the three groups.

All patients underwent MRI at 3T on an Achieva system from Philips Medical Systems. Heat-pain stimulation was provided by an MR-compatible Peltier-type device (Medoc TSA-II). Whole-brain susceptibility-weighted datasets were acquired using a single-shot, gradient-recalled echo-planar technique (TE = 35 ms, TR = 3000 ms, SENSE factor 1.5). Images were postprocessed offline using statistical parametric mapping.

"Analysis indicated significant differences in the brain's BOLD hemodynamic response to heat-pain between diabetic subjects. Those without neuropathy showed greater response than those with DPN," Wilkinson wrote. "For those with DPN, patients with painful neuropathy showed significantly greater response than those with painless neuropathy."

The anatomical areas involved included the primary somatosensory cortex and lateral frontal and cerebella regions.

The study indicates that the brain's response to externally applied acute heat-pain stimulation is different for diabetic patients with and without DPN. These differences occur within the frontal lobe, which is often associated with high-level perception and cognitive function, as well as the cerebellum, which may implicate processing speed action.

"It remains unclear whether the observed differences in BOLD response to acute heat-pain stimulation DPN are associated with intracranial pathology, spinal dysfunction, or peripheral nerve generation," the authors concluded.