Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Rubin reports he is a consultant for Merck Sharp & Dohme Corp.

SYNOPSIS: Carpal tunnel syndrome (CTS), when seen in the very elderly, is usually severe and is not reliably diagnosed by ultrasound. Nerve conduction studies and electromyography are the most sensitive and specific tests to make accurate diagnosis of CTS.

SOURCE: Mulroy E, Pelosi L. Carpal tunnel syndrome in advanced age: A sonographic and electrodiagnostic study. Muscle Nerve 2019; Apr. 26. doi: 10.1002/mus.26496. [Epub ahead of print].

Affecting 1-5% of the population, with a 3:1 female:male ratio, carpal tunnel syndrome (CTS) is the most common entrapment neuropathy, occurring most often in obese women, and least so in thin men. Diabetes, hypothyroidism, and rheumatoid arthritis, as well as pregnancy and aromatase inhibitors, are associated with CTS, but evidence that age plays a factor is controversial. Diagnosis usually is confirmed by electrodiagnostic studies, with ultrasonography showing a significantly increased cross-sectional area of the median nerve compared to controls, offering a painless way of making the diagnosis. However, ultrasound may not be reliable in the very elderly.

Data from all patients referred to the Department of Clinical Neurophysiology, Auckland, New Zealand, between May 2014 and May 2015, who had undergone both electrodiagnostic and ultrasonographic studies of the median nerve, were reviewed retrospectively and divided selectively into two age groups, 40-65 years and 80-95 years. Electrodiagnostic studies conformed to recommendations of the American Association of Neuromuscular and Electrodiagnostic Medicine, and, to minimize operator bias, in all instances were preceded by ultrasound evaluation of the median nerve, performed by the same operator, consisting of evaluating the maximum median nerve cross-sectional area at the wrist as well as wrist-to-forearm ratio. Statistical analysis comprised Pearson’s correlation coefficient and Shapiro-Wilk and Student t-tests.

Among a total of 92 patients and 110 hands included in the study, 59 were 40-65 years of age and 33 were 80-95 years of age. CTS was more severe, both clinically and electrodiagnostically, in the very elderly, whereas, paradoxically, maximal median nerve cross-sectional area at the wrist was significantly larger in the younger group.

Additionally, as CTS severity worsened in the younger group, so too did maximal median nerve cross-sectional area increase at the wrist, whereas this correlation was not seen in the elderly group. Mid-forearm median nerve cross-sectional area was similar in both age groups. Sensitivity of nerve ultrasound was significantly lower in the elderly group, with 46% of clinically abnormal hands and 39% of electrodiagnostically abnormal hands having normal ultrasound median nerve cross-sectional area measurements. No correlation was found in the elderly group between ultrasound and electrodiagnostic measurements. Electrodiagnostic testing was 100% sensitive in both groups with clinically moderate or severe CTS.

COMMENTARY

Despite a high prevalence, the etiology of CTS often remains uncertain. In 2002, a twin study in the United Kingdom suggested that the strongest risk factors for CTS in women were genetic.¹ Recently, the authors of a genome-wide association study, using 12,312 CTS cases and 389,344 controls from in the UK Biobank resource, identified 16 novel susceptibility loci for CTS, suggesting that genetic variants implicated in skeletal growth and extracellular matrix architecture alter the environment through which the median nerve traverses, thus predisposing to CTS. Mendelian randomization analysis revealed a causal association between short stature and a higher risk for CTS, with CTS patients, on the average, 2 cm shorter than controls. Connective tissue abnormalities appear causally connected to carpal tunnel syndrome.²

REFERENCES

1. Hakim AJ, Cherkas L, El Zavat S, et al. The genetic contribution to carpal tunnel syndrome in women: A twin study. Arthritis Rheum 2002;47;275-279.
2. Wiberg A, Ng M, Schmid A, et al. A genome-wide association analysis identifies 16 novel susceptibility loci for carpal tunnel syndrome. Nat Commun 2019; Mar. 4. doi: 10.1038/s41467-019-08993-6.