Case study of an amputee regaining sensation and muscle function in a residual limb after peripheral nerve stimulation by intense focused ultrasound

C.K. Ezeokeke, M.S. Bobola, M. Selby, J.H. Ko, J.L. Friedly, P.D. Mourad

Brain Stimulation 2020 · 10.1016/j.brs.2020.01.003

human patientotherbehaviour

Specieshuman

Subjects1 participants

Sessions per subject1

Randomisedno

Blindingsingle

Sham / controlnone

Auditory controlnot reported

Readout timingonline

Anaesthesianot applicable

Readoutsbehaviour — Clinical observation and participant report of voluntary/involuntary muscle movement and cutaneous sensation; real-time diagnostic ultrasound imaging used to guide stimulation and to directly observe muscle movement

Direction of effectexcitatoryiFU stimulation of the non-functioning tibial nerve produced phantom limb sensations and, at a second intensity, involuntary followed by voluntary movement of the lateral gastrocnemius muscle and recovered cutaneous sensation, restoring motor and sensory function that had been absent since TMR surgery.

Adverse eventsnot reported

Exposures

Exposure 1: iFU stimulation of the tibial nerve

Target: tibial nerve — “non-functioning tibial nerve (distal transected nerve after TMR)”
Device: custom-built

Pulse timing
Waveform	continuous
Fundamental frequency (kHz)	2,000	✓✓✓
Pulse duration (ms)	not applicable
Pulse repetition frequency (Hz)	not applicable
Duty cycle (%)	not applicable
Sonication duration (s)	0.1	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	not reported
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported
Ispta, domain unspecified (W/cm²)	71.5, 66.5swept	✓✓✓

Protocol, in the paper’s words

Five individual 0.1-second iFU pulses were delivered per intensity value, spaced 1-2 seconds apart, using a ramp-up paradigm starting at low intensity and increasing until a first discernible sensation was achieved; after an initial 71.5 W/cm2 exposure, stimulation continued at a lower intensity (66.5 W/cm2) within 1 minute.

Exposure 2: iFU stimulation of the peroneal nerve

Target: peroneal nerve — “transected peroneal nerve”
Device: custom-built

Pulse timing
Waveform	continuous
Fundamental frequency (kHz)	2,000	✓✓✓⚑
Pulse duration (ms)	not applicable
Pulse repetition frequency (Hz)	not applicable
Duty cycle (%)	not applicable
Sonication duration (s)	0.1	✓✓✓

Pressure and intensity, by domain
Free-field pressure (kPa)	not reported
Free-field Isppa (W/cm²)	not reported
Free-field Ispta (W/cm²)	not reported
In-situ estimate	not reported
In-situ pressure (kPa)	not reported
In-situ Isppa (W/cm²)	not reported
In-situ Ispta (W/cm²)	not reported
Ispta, domain unspecified (W/cm²)	66.5	✓✓✓

Protocol, in the paper’s words

During the same session, the transected peroneal nerve was successfully stimulated at a comparable intensity value (66.5 W/cm2) as used for the tibial nerve.

Flags from extraction

exposures[0].unspecified_domain.isppa_w_cm2 — Paper labels this value 'spatial peak temporal average intensity' (which matches the schema's ispta_w_cm2 field name), but it is placed in isppa_w_cm2 because it is delivered as five discrete 0.1 s pulses rather than a continuous exposure long enough for a temporal-average interpretation to be unambiguous; flagged for reviewer judgement. No domain (free-field vs in-situ) is stated, so placed in unspecified_domain.
exposures[1].fundamental_frequency_khz — The 2.0 MHz frequency is stated explicitly only for the tibial nerve stimulation; the peroneal nerve stimulation used 'a comparable intensity value' with the same device in the same session, and frequency was not independently restated for it.
conditions — No vocabulary term covers post-amputation/TMR peripheral nerve injury; classified as other with condition_other text.