Utility of recovery cycle with two conditioning pulses for detection of impaired axonal slow potassium current in ALS

Objective

Slow potassium current (I_Ks) is important in controlling nerve excitability and its impairment is known in various neurological diseases, including amyotrophic lateral sclerosis (ALS). I_Ks gives rise to the late subexcitability phase of the recovery cycle, which can be amplified by the use of multiple conditioning pulses. The clinical utility of this technique has not previously been explored.

Methods

Nerve excitability tests, including recovery cycles with single and double conditioning pulses 4 ms apart (RC and RC2, respectively) were performed in patients with ALS and control subjects. Late subexcitability values obtained by RC and RC2 were compared in both groups.

Results

RC2 was well tolerated in all the subjects. The threshold changes in late subexcitability by RC2 were greater than those by RC in both groups (mean (%): RC, 16.0/13.3; RC2, 34.9/29.4 (Control/ALS)). The ALS group showed lower threshold changes than controls by both methods. Statistical analysis between the ALS and control groups provided smaller P value by RC2 (P = 0.018) than by RC (P = 0.046). Also, RC2 provided non-significant, but slightly more distinguishing non-parametric rank analysis and greater Area Under the Curve (AUC) by Receiver Operating Characteristic (ROC). RC2 produced more identifiable single peak for late subexcitability than RC in an ALS patient whose late subexcitability was decreased.

Conclusions

Two conditioning stimuli provide greater threshold change for late subexcitability and possibly clearer identification of a peak threshold change than conventional recovery cycle. The findings obtained by this new protocol reinforce the previously reported impairment of I_Ks in ALS.

Significance

Amplification of I_Ks by double conditioning pulses is applicable in humans and may help elucidating its clinical significance in pathophysiology in neurological diseases.