This prospective study was approved by the Institutional Review Board (IRB), Faculty of Medicine (code number: R/19.04.483), and (the ClinicalTrials.gov identifier: NCT04454541) all patients had a written informed consent.
The study was performed in the period between May 2019 and December 2019 at out-patient clinics of the Neurology Department, University Hospital.
Sixty patients were included in this study. All 60 patients had cervicogenic headache disorders which were diagnosed according to the criteria of the International Classification of Headache Disorder version III (ICHD-III beta version) [3].
This study included patients from both sexes, and patients’ ages were more than or equal to 18 years old.
Younger age patients, patients not fulfilling the criteria of cervicogenic headache ICHD-III beta version, patients with a history of occipital nerve stimulation, patients with a history of occipital nerve injection, patients with a history of any occipital region surgical intervention, patients with a history of allergic reaction to any of materials used in the procedures, pregnant or lactating patients, patients with uncontrolled hypertension, patients with uncompensated congestive heart failure, patients with uncontrolled diabetes mellitus, patients with chronic liver disease, patients with chronic renal failure, patients with infectious and/or inflammatory diseases, patients with neoplasm and/or vascular disease, and patients with antiplatelet or anticoagulant therapy that may interfere with the procedure were excluded from this study.
Before the procedure, a full clinical neurological examination was performed on all patients. Routine laboratory investigations were done for all patients like renal function tests, liver function tests, complete blood count, and measurement of prothrombin time (PT) and activated partial thromboplastin time (APTT). Electrocardiography (ECG) was done for all patients. Measurement of saturation of pulse oxygen (SpO2) was done for all patients.
Pain intensity was evaluated for all patients according to the visual analog scale (VAS) (0–10) (the pain VAS is a uni-dimensional, widely used scale in the measurement of the intensity of the pain comprising a horizontal (HVAS) or vertical (VVAS) line, usually 10 cm (100 mm) in length) [18, 19].
Pain intensity evaluation was performed at the time of the initial diagnosis and performed later at the 2nd and 4th weeks after the procedures. The evaluation was performed by using the VAS for the side that affected by cervicogenic headache in a blinded manner.
Primary outcome headache-free interval 30 min after the procedure is described as a decrease of pain intensity about 30% from the basal procedure level.
All procedures were performed using an ultrasound machine (Logiq. P5 pro model, GE brand, GE health care, France manufacture) with a high-frequency linear array transducer (7–15 MHz); the US machine provided adequate penetration with a high-resolution image. The scanning was done in both transverse and longitudinal planes. Real-time ultrasound imaging was done by using both gray-scale and color Doppler techniques for accurate occipital artery localization.
Interventional procedures
Before the procedure, upper extremity venous access was established in all patients of both groups. Blood pressure (BP) and heart rate (HR) were measured for all patients. Electrocardiogram (ECG) was done for all patients, and pulse oxygen saturation (SpO2) was also measured for all patients.
Before the procedure, all patients were infused with intravenous Ringer’s solution 2 mL/kg/h and continuing low-flow of non-humidified oxygen (2 L/min) with a nasal cannula. During the procedure, respiratory signs were monitored closely.
Greater occipital nerve block
The patient was lying in a prone position. For accurate localization of the occipital nerve, ultrasound-guided GONB was done by using a linear transducer that was sheathed in a sterile plastic package. To locate the occipital nerve, we searched first for the occipital artery in the medial one-third of the superior nuchal line in the area between the occipital tubercle and mastoid process by using both gray-scale and color Doppler ultrasound techniques (Fig. 1).
Before the injection, the scalp was cleaned with iodine, and the skin was sterilized.
In all patients, the occipital nerve was seen just medial to the occipital artery. Greater occipital nerve block was done by applying the injection just medial to the occipital artery by using a 22-gauge needle that was advanced beneath the lateral border of the ultrasound linear transducer with real-time ultrasound guidance and an in-plane technique.
We detected the injected side according to the clinical symptoms of the patients and the painful side reported in the patients’ headache complaint. During the procedure, we injected 10 ml of 0.5% isobaric bupivacaine. After injection, the patients were asked to lie down for 30 min to avoid dizziness.
Multifidus cervicis plane block (MCPB) group
The patient was asked to lie in a lateral position with the affected side directed upwards. Multiple gel cushions were placed under the patient’s head, neck, and arm in order to make the patient’s neck in a stable and mildly anterior flexion position. We determined the spinal level by the identification of the transverse process of the seventh and sixth cervical vertebrae (C7 and C6). The seventh cervical transverse process (C7) differs from the cervical vertebrae above by the presence of a rudimentary anterior tubercle and a prominent posterior tubercle. The transverse process of the sixth cervical spine with its characteristic sharp anterior tubercle could be visualized by moving the ultrasound transducer cranially; this allows for the easy identification of the consecutive cervical segments.
Before the procedure, all aseptic preparations of the injection area were done, and we used lidocaine 1% to anesthetize the skin.
The needle (22-G, 0.7 mm × 60 mm, Plexufx, B-BRAUN, Tokyo, Japan) was introduced in-plane through the skin under continuous ultrasound guidance. The needle was advanced into the fascial plane between the semispinalis cervicis and multifidus cervicis muscles for the MCP block by injection of 20 ml of 0.5% isobaric bupivacaine (Fig. 2).
After the procedure, all patients were continuously monitored by non-invasive monitoring 1 h before discharge to home.
Informed consent
All patients had a written consent before they were included in this study, and these consents were done after a complete explanation of the procedure steps, side effects, complications, and hoping benefits for all patients.
Statistical analysis
We used the clinical outcome variables for the intention-to-treat analysis. The data were presented as means and standard deviations (SD). The comparison between the studded groups was carried out using the t test, analysis of variance (ANOVA) with the Tukey test, Honestly Significantly Different (HSD) test, Cochran-Armitage trend test, and Kruskal-Wallis test. Hommel’s adjustments were carried out to correct the significance levels for multiple and post hoc testing. Hodges-Lehmann estimate of the median difference with a 95% confidence interval (95% CI) was used to determine the differences in the clinical variable outcome. The normality of variables was evaluated using the Shapiro-Wilk statistic.
The predictors of cervicogenic headache were determined by VAS through the conduction of a correlation analysis. Descriptive statistics, including frequency distributions for categorical variables, medians, and quartiles one and three (Q1, Q3) for continuous variables, were used for the characterization of the study sample at baseline assessment. Score changes between baseline and follow-up visits were assessed by comparing the frequency and median distributions at each time point, in the overall samples, and stratified by whether or not participants were deemed responders. For all analyses, P values are two-sided, and the significance level was set at 0.05. The α level was set at 0.05 for all tests.
A prior G-power analysis was done using the results obtained from previous studies and assuming alpha error of 0.05 and beta error of 0.2 (power of the study 80%). A sample size of 30 patients per each group was calculated.