Sural Nerves Implicated in ALS

Read any overview of amyotrophic lateral sclerosis (ALS) and you will learn that ALS affects motor nerves but not sensory nerves-but is this correct? A study by an investigative team in the Department of Neurology at Emory University in Atlanta suggests that sural nerves indeed are affected. In reviewing cases entered into the Emory University motor neuron disease registry between 1997 and 2004, the team discovered that sural sensory nerve action potential (SNAP) amplitudes were abnormal in 36.4% (8 of 22) of sural nerve biopsies, with a mean reduction in amplitude of 35.5%. Furthermore, pathologic abnormalities, predominantly affecting large-caliber myelinated fibers, were present in 91% (21 of 22) of these biopsy specimens. SNAP amplitudes also were analyzed in 81 patients with ALS whose records included data on sural nerve studies but not biopsies. SNAP amplitudes were reduced in 21aeor about a quarter (25.9%)aeof these patients. The mean reduction in amplitude was 49.6%. "Age and gender distributions as well as the frequency of sural sensory nerve conduction abnormalities and mean reduction in SNAP amplitudes were similar in the [biopsy] and [no biopsy] groups, suggesting that the patients undergoing biopsy were representative of the broader ALS population," the team explained in a poster that they presented last year at the annual meeting of the American Neurological Association in San Diego. A CLINICAL PROBLEM OR NOT? A handful of small studies have emerged since the 1980s suggesting that sural nerves might be affected by ALS. Some suggest that an effect is present but subtle if not minor,1,2 while others suggest that sural nerve involvement is significant.3,4 Indeed, a very early study3 of 5 patients with "pseudopolyneuropathic" ALS generated findings similar to those of the Emory researchers. Sural nerve biopsies demonstrated "a severe loss" of myelinated fibers, with large fibers being most affected. In addition, "wallerian-like degeneration" was evident in teased fibers. The authors of the early study concluded that axonal degeneration of the sural nerve is evident in pseudopolyneuropathic forms of ALS. Another study that found abnormalities in sensory as well as motor nerve conduction velocities in patients with ALS suggested that nerve entrapment might be a contributing cause of sensory nerve involvement but that other factors, yet unexplained, also might be involved.5 In addition to capturing evidence of ALS-associated axonal degeneration of sural nerves, the Emory team identified 4 patterns of degeneration: irregular myelin; wallerian, which was the most predominant pattern; segmental demyelination; and intermodal variability of more than 50%. A blind reexamination by 3 neuromuscular pathologists of sural nerve biopsy specimens from patients both with and without ALS was undertaken to determine this finding as well as confirm the diagnosis. Patterns were elicited by teased fiber analysis of 7 biopsies in which demyelination was suspected (6 from patients with ALS and 1 from a control) before unblinding. A RESEARCHER SPEAKS Applied Neurology recently posed several questions to the lead author of the study, Mustafa Hammad, MD, DO, a fellow at Emory during the time of the study and currently an attending physician at Bay Medical Center in Panama City, FL. The exchange appears below in Q&A format: AN: Why did you and your colleagues decide to embark on this study? Hammad: ALS is a progressive degenerative disease of the upper and lower motor neurons. Although it is thought to be a pure motor neuron disease, many autopsy studies have shown involvement of the non-motor pathways, both in the familial and in sporadic forms. Sensory nerve involvement was suggested decades ago when Bertrand and van Bogaert6 mentioned in their neuropathology report of Charcot ALS that in the peripheral nerve "the sensory fibers are as poor in myelin as are motor fibers." Since then, sensory nerve involvement has been suggested by a number of morphologic, electrophysiologic, and quantitative sensory studies. However, those studies had small sample size, inconsistent results, and none reported both physiologic and pathologic changes in the same patients. The objective of this study was to assess the pathologic and electrophysiologic sensory nerve abnormalities in patients with ALS. AN: How did the neuropathologists "score" in identifying the pathologic biopsy specimens? Hammad: We had 22 ALS and 12 control sural nerve biopsies. The controls are biopsy specimens from patients with myopathy, fatigue, generalized weakness, or other nonspecific symptoms. Those control biopsies were interpreted as normal when they were initially read. All biopsies were randomly