Introduction
Methods
Patients
Study design
Surgery and stimulation
Outcome and statistical analysis
Results
Study population
Center/patient no. | Group | Sex | Age (years) | Disease duration (years) | Attack side | Onset clinical form | Attacks/week | Pain intensity | Sumatriptan injection/week | Oxygen use |
---|---|---|---|---|---|---|---|---|---|---|
C1/P1 | On/Off | M | 52 | 35 | Left | Episodic | 14 | 9 | 1 | No |
C1/P2 | Off/On | M | 40 | 12 | Right | Chronic | 14 | 5 | 14 | No |
C1/P3 | Off/On | M | 51 | 8 | Left | Episodic | 19 | 2 | 15 | No |
C1/P4 | On/Off | M | 44 | 10 | Left | Chronic | 28 | 10 | 0 | No |
C1/P5 | On/Off | M | 47 | 7 | Right | Chronic | 11 | 6 | 11 | No |
C2/P1 | Off/On | M | 50 | 20 | Right | Episodic | 20 | 5 | 0 | No |
C2/P2 | Off/On | F | 42 | 3 | Left | Chronic | 7 | 8 | 1 | Yes |
C3/P1 | On/Off | F | 42 | 7 | Right | Episodic | 53 | 6.5 | 0 | Yes |
C3/P2 | Off/On | M | 36 | 7 | Left | Chronic | 9 | 5 | 11 | No |
C4/P1 | Off/On | M | 39 | 18 | Right | Episodic | 14 | 5 | 14 | No |
C4/P2 | On/Off | F | 43 | 6 | Right | Chronic | 7 | 7 | 1 | Yes |
Mean | 44.1 | 12.1 | 17.8 | 6.1 | 6.2 |
Effect of electrode implantation
Effect of the stimulation during the randomized phase
Active stimulation followed by sham stimulation (On–Off group) (n = 5) Median [range] | Sham stimulation followed by active stimulation (Off–On group) (n = 6) Median [range] | Difference between active and sham stimulation in the On–Off group Mean [95% CI] | Difference between active and sham stimulation in the Off–On group Mean [95% CI] | P value (treatment effect) | |||||
---|---|---|---|---|---|---|---|---|---|
Baseline (week 8) | End of On period (week 12) | End of Off period (week 17) | Baseline (week 8) | End of Off period (week 12) | End of On period (week 17) | ||||
Attacks/week | 11 [2–42] | 18 [1–55] | 6 [1–49] | 16 [7–25] | 14.5 [0–28] | 9 [6–21] | 0.2 [−24.0; 23.6] | −2.7 [−25.7; 20.31] | 0.927 |
Sumatriptan (injection/week) | 7 [1–13] | 0 [0–18] | 1 [0–6] | 11.5 [1–29] | 12.5 [0–33] | 6.5 [0–25] | 2 [−9.0; 13] | −5.3 [−24.1; 13.5] | 0.349 |
Pain intensity | 5.5 [4–9] | 5 [3–8] | 5.5 [3–8] | 6 [2–9] | 5.7 [0–10] | 4.5 [2–9] | 0 [−1.4; 1.4] | 0.3 [−9.5; 10] | 0.357 |
PGIC | na | 2 [1–7] | 2 [1–6] | na | 2 [1–4] | 4 [1–7] | 0.8 [−20.1; 21.8] | 1.3 [−4.2; 6.8] | 0.853 |
HAD-A | 8.8 [5–10] | 8 [3–12] | 6 [4–14] | 11.5 [6–15] | 8 [5–10] | 9 [6–15] | 0.2 [−23.6.1; 24.0] | −2.6 [−25.5; 20.3] | 0.927 |
HAD-D | 8.5 [3–13] | 9 [4–13] | 1 [0–6] | 9.5 [1–13] | 4 [1–9] | 8 [1–16] | 1.3 [−22.4; 25.1] | 5.3 [−1.08; 11.7] | 0.154 |
SF 12-MS | 33.1 [28.1–52.1] | 34.5 [31.6–56.2] | 30.3 [17.8–59.9] | 36.4 [27.5–53.3] | 48.9 [24.9–54.2] | 36.7 [16–52.9] | 5.8 [−12.8; 24.4] | −8.7 [−27.3; 9.9] | 0.197 |
SF 12-PS | 29 [24.4–31.2] | 28.3 [27.2–29.0] | 33.8 [27.5–34.9] | 34.7 [32.2–46.5] | 37.9 [28.4–46.5] | 43.4 [28.1–51.5] | −3.9 [−13.1; 5.3] | 2.8 [−15.4; 21] | 0.197 |
Effect of the stimulation during the open phase
Before implantation (week 4) Median [range] | End of open phase (week 52) Median [range] | Difference between end of open phase and baseline Mean [95% CI] | P value | |
---|---|---|---|---|
Attacks/week | 14 [7; 53] | 8 [0; 23] | 8.16 [–18.3; 34.7] | 0.082 |
Pain intensity | 6 [2; 10] | 4.5 [0; 10] | 1.1 [–7.1; 9.3] | 0.499 |
Sumatriptan (injections/week) | 1 [0; 15] | 0.5 [0; 26] | –0.1 [–11.3; 11.1] | 0.288 |
HAD-A | 13 [5; 18] | 7.5 [0; 14] | 6.3 [–5.1; 17.7] | 0.008 |
HAD-D | 10 [1; 16] | 4.5 [1; 15] | 4.1 [–6.48; 14.7] | 0.052 |
SF12-MS | 33.2 [27.5; 53.3] | 37.0 [20.7; 56.6] | –0.6 [–26.5; 25.2] | 0.953 |
SF12-PS | 32.7 [24.4; 46.5] | 39.7 [25.2; 50.5] | 4.3 [–16.7; 25.3] | 0.173 |
Patient | Long-term responder | Before implantation | 1-year follow-up |
---|---|---|---|
C1P1 | Yes | Verapamil 240 mg | No treatment |
Lithium 800 mg | |||
C1P2 | No | Verapamil 1440 mg | Verapamil 1440 mg |
C1P3 | No | Verapamil 1200 mg | Verapamil 1200 mg |
C1P4 | Yes | Verapamil 600 mg | Verapamil 1080 mg |
Lithium 400 mg | |||
C1P5 | No | Verapamil 720 mg | No treatment |
Lithium 800 mg | |||
C2P1 | Yes | Verapamil 960 mg | Verapamil 360 mg |
Lithium 1000 mg | Lithium 500 mg | ||
C2P2 | Yes | Lithium 800 mg | Divalproex 1500 mg |
Fluoxetine 40 mg | |||
C3P1 | Yes | Verapamil 360 mg | Verapamil 360 mg |
Prednisone 20 mg | |||
C3P2 | No | Verapamil 480 mg | Verapamil 480 mg |
C4P1 | Yes | Verapamil 720 mg | Verapamil 720 mg |
C4P2 | No | No | Verapamil 240 mg |
Adverse events
AE related to surgery | 2 |
Superficial infection (hardware removal) (SAE) | 1 |
Neck pain along the lead | 1 |
Transient AE related to test stimulation (Resolving after voltage reduction or contact change) | 5 |
Complex oculomotor disturbancesa | 4 |
Loss of consciousness with hemiparesia (SAE) | 1 |
AE and changes during “On” period | 6 |
Mild hunger increase | 3 |
Mild hunger decrease | 1 |
Mild libido decrease | 2 |
AE and changes during “Off” period | 8 |
Mild hunger increase | 2 |
Mild hunger decrease | 1 |
Mild thirst increase | 1 |
Mild thirst decrease | 1 |
Mild libido decrease | 1 |
Increased testosterone level | 1 |
Shorten menstrual cycle | 1 |
AE and changes related to chronic stimulation | 8 |
Facial flush attacks | 1 |
Changes in blood pressure response to posture | 1 |
Severe micturition syncopes (SAE) | 1 |
Basal blood pressure changes | 0 |
Basal heart rate changes | 0 |
Body temperature changes | 0 |
Moderate weight increase (5 kg) | 1 |
Mild hunger increase | 1 |
Mild hunger decrease | 1 |
Mild libido decrease | 1 |
Significant electrolyte changes | 0 |
Increased testosterone level | 1 |
Other significant hormonal changes | 0 |