Can McArdle’s Sign Help Diagnose MS?

PARIS—McArdle’s sign, a rapidly reversible motor weakness induced by head flexion in patients with suspected multiple sclerosis (MS), may facilitate diagnosis in certain clinical situations, according to a study presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. “McArdle’s sign, when defined as a greater than 10% neck flexion-induced reduction using isoinertial finger extension on a measurement device, is highly specific and moderately sensitive for a diagnosis of MS,” said Brian G. Weinshenker, MD, and colleagues. Dr. Weinshenker is Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.

Dr. Weinshenker and colleagues quantified McArdle’s sign in finger extensors using a torque measuring device and assessed its specificity for MS. They enrolled 25 healthy controls and 76 patients with detectable finger extensor weakness, 52 with MS, 24 with other myelopathies, and five with peripheral nerve lesions. Patients were not selected for having McArdle’s sign. Dr. Weinshenker and his team evaluated McArdle’s sign blinded to diagnosis by measuring change in finger extensor strength in successive trials of head extension and flexion, first clinically and then with a torque measuring device. McArdle’s sign was clinically rated from zero (absent) to three (marked). In the quantitative measurement, the patient applied maximum extension strength of four fingers on a bar using isometric (against fixed object) and isoinertial (against a constant resistance) maneuvers. The researchers then averaged the percentage decrease in strength over four trials.

Baseline strength was similar in the three patient groups. The median clinical McArdle’s sign was one (range, zero to three) in patients with MS, zero (range, zero to two) in other myelopathies, zero (range, zero to one) in healthy controls, and zero in all patients with peripheral nerve lesions. The isometric and isoinertial maneuvers provided similar quantitative results, but the isoinertial maneuver had superior diagnostic performance. Head flexion resulted in 17% (± 17%) isoinertial strength reduction in patients with MS versus 1% (± 6%) in other myelopathies, 1% (± 5%) in healthy controls and -3% (± 10%) in patients with peripheral nerve lesions.

A multivariate regression analysis eliminated confounding by baseline strength. Receiver operator curves were generated to assess the diagnostic properties of the test; the area under the curve was 0.82 in patients with MS versus healthy controls and 0.83 in patients with MS versus other myelopathies for isoinertial testing. A 10% drop in strength with flexion was 100% specific and 62% sensitive for MS compared with other myelopathies and a 6% drop, 92% specific and 73% sensitive, for MS compared with healthy controls. Quantitative McArdle’s sign correlated with clinical McArdle’s sign by referring physician and technician (r = 0.58). McArdle’s sign correlated with Expanded Disability Status Scale (r = 0.41) and pyramidal score (r = 0.49) in patients with MS, but was evident in some patients in very early phases of MS and minor disability.

PARIS—McArdle’s sign, a rapidly reversible motor weakness induced by head flexion in patients with suspected multiple sclerosis (MS), may facilitate diagnosis in certain clinical situations, according to a study presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. “McArdle’s sign, when defined as a greater than 10% neck flexion-induced reduction using isoinertial finger extension on a measurement device, is highly specific and moderately sensitive for a diagnosis of MS,” said Brian G. Weinshenker, MD, and colleagues. Dr. Weinshenker is Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.

Dr. Weinshenker and colleagues quantified McArdle’s sign in finger extensors using a torque measuring device and assessed its specificity for MS. They enrolled 25 healthy controls and 76 patients with detectable finger extensor weakness, 52 with MS, 24 with other myelopathies, and five with peripheral nerve lesions. Patients were not selected for having McArdle’s sign. Dr. Weinshenker and his team evaluated McArdle’s sign blinded to diagnosis by measuring change in finger extensor strength in successive trials of head extension and flexion, first clinically and then with a torque measuring device. McArdle’s sign was clinically rated from zero (absent) to three (marked). In the quantitative measurement, the patient applied maximum extension strength of four fingers on a bar using isometric (against fixed object) and isoinertial (against a constant resistance) maneuvers. The researchers then averaged the percentage decrease in strength over four trials.

Baseline strength was similar in the three patient groups. The median clinical McArdle’s sign was one (range, zero to three) in patients with MS, zero (range, zero to two) in other myelopathies, zero (range, zero to one) in healthy controls, and zero in all patients with peripheral nerve lesions. The isometric and isoinertial maneuvers provided similar quantitative results, but the isoinertial maneuver had superior diagnostic performance. Head flexion resulted in 17% (± 17%) isoinertial strength reduction in patients with MS versus 1% (± 6%) in other myelopathies, 1% (± 5%) in healthy controls and -3% (± 10%) in patients with peripheral nerve lesions.

A multivariate regression analysis eliminated confounding by baseline strength. Receiver operator curves were generated to assess the diagnostic properties of the test; the area under the curve was 0.82 in patients with MS versus healthy controls and 0.83 in patients with MS versus other myelopathies for isoinertial testing. A 10% drop in strength with flexion was 100% specific and 62% sensitive for MS compared with other myelopathies and a 6% drop, 92% specific and 73% sensitive, for MS compared with healthy controls. Quantitative McArdle’s sign correlated with clinical McArdle’s sign by referring physician and technician (r = 0.58). McArdle’s sign correlated with Expanded Disability Status Scale (r = 0.41) and pyramidal score (r = 0.49) in patients with MS, but was evident in some patients in very early phases of MS and minor disability.

PARIS—McArdle’s sign, a rapidly reversible motor weakness induced by head flexion in patients with suspected multiple sclerosis (MS), may facilitate diagnosis in certain clinical situations, according to a study presented at the Seventh Joint ECTRIMS–ACTRIMS Meeting. “McArdle’s sign, when defined as a greater than 10% neck flexion-induced reduction using isoinertial finger extension on a measurement device, is highly specific and moderately sensitive for a diagnosis of MS,” said Brian G. Weinshenker, MD, and colleagues. Dr. Weinshenker is Professor of Neurology at the Mayo Clinic in Rochester, Minnesota.

Dr. Weinshenker and colleagues quantified McArdle’s sign in finger extensors using a torque measuring device and assessed its specificity for MS. They enrolled 25 healthy controls and 76 patients with detectable finger extensor weakness, 52 with MS, 24 with other myelopathies, and five with peripheral nerve lesions. Patients were not selected for having McArdle’s sign. Dr. Weinshenker and his team evaluated McArdle’s sign blinded to diagnosis by measuring change in finger extensor strength in successive trials of head extension and flexion, first clinically and then with a torque measuring device. McArdle’s sign was clinically rated from zero (absent) to three (marked). In the quantitative measurement, the patient applied maximum extension strength of four fingers on a bar using isometric (against fixed object) and isoinertial (against a constant resistance) maneuvers. The researchers then averaged the percentage decrease in strength over four trials.

Baseline strength was similar in the three patient groups. The median clinical McArdle’s sign was one (range, zero to three) in patients with MS, zero (range, zero to two) in other myelopathies, zero (range, zero to one) in healthy controls, and zero in all patients with peripheral nerve lesions. The isometric and isoinertial maneuvers provided similar quantitative results, but the isoinertial maneuver had superior diagnostic performance. Head flexion resulted in 17% (± 17%) isoinertial strength reduction in patients with MS versus 1% (± 6%) in other myelopathies, 1% (± 5%) in healthy controls and -3% (± 10%) in patients with peripheral nerve lesions.

A multivariate regression analysis eliminated confounding by baseline strength. Receiver operator curves were generated to assess the diagnostic properties of the test; the area under the curve was 0.82 in patients with MS versus healthy controls and 0.83 in patients with MS versus other myelopathies for isoinertial testing. A 10% drop in strength with flexion was 100% specific and 62% sensitive for MS compared with other myelopathies and a 6% drop, 92% specific and 73% sensitive, for MS compared with healthy controls. Quantitative McArdle’s sign correlated with clinical McArdle’s sign by referring physician and technician (r = 0.58). McArdle’s sign correlated with Expanded Disability Status Scale (r = 0.41) and pyramidal score (r = 0.49) in patients with MS, but was evident in some patients in very early phases of MS and minor disability.