Botulinum Toxin and/or Greater Occipital Nerve Block for Patients With Chronic Migraine
Phase: NA
Conditions: Chronic Migraine Headache, OnabotulinumtoxinA, Greater Occipital Nerve Block, Combination Therapy
Sponsor: Beni-Suef University

 
Botulinum toxin and/or Greater Occipital Nerve Block for Patients with 
Chronic Migraine 
 
Thesis Submitted for Partial Fulfillment of Master Degree in Neurology 
Prepared by  
Rakia Mohamed Taha Basiouny 
(M.B.B.CH) 
Faculty of Medicine - October 6 University 
Under supervision of 
Dr. Amr Hassan Al Sayed 
Professor of Neurology  
Kasr Al Ainy Faculty of Medicine – Cairo University  
 
Dr. Mona Hussein Tawfik 
Professor of Neurology 
Faculty of Medicine - Beni-Suef University 
Dr. Mona Ali Abosrea 
Lecturer of Neurology 
Faculty of Medicine - Beni-Suef University 
Faculty of Medicine 
Beni-Suef University 
2026 
Official Title:Botulinum Toxin and/or Greater Occipital Nerve Block for Patients With Chronic Migraine 
Protocol ID:RakiaBasiouny97$ 
Date:April 2026 
NCT Number:Not yet assigned 

 
1 
 
Introduction 
Chronic migraine (CM) is a highly disabling neurological disorder affecting 
approximately 1–2% of the global population and about 8% of individuals with 
migraine (Global Burden of Disease Collaborators, 2017; Karaoğlan et al., 
2022). The consequences of CM extend beyond pain, imposing substantial 
functional, psychological, and socioeconomic challenges. Individuals with CM 
usually experience significant impairments in daily functioning, reduced health-
related quality of life, and diminished productivity (Serrano et al., 2013; Ford 
et al., 2021). The condition contributes to considerable healthcare costs, 
emphasizing the need for effective preventive therapeutic strategies (Bonafede 
et al., 2018). 
Management of CM is multifaceted, encompassing acute, preventive, and 
non-pharmacologic strategies. Acute therapies, including triptans and 
nonsteroidal anti-inflammatory drugs (NSAIDs), are often limited by 
medication overuse, which itself is a risk factor for chronification (Bigal & 
Lipton, 
2009). 
Preventive 
pharmacotherapy 
includes 
beta-blockers, 
anticonvulsants (e.g., topiramate), tricyclic antidepressants, and more recently, 
monoclonal antibodies targeting the CGRP pathway (Schwedt, 2018). Non-
pharmacologic strategies such as cognitive-behavioral therapy (CBT), 
biofeedback, and relaxation training are increasingly recognized as essential 
adjuncts in CM management. Lifestyle modifications including avoidance of 
migraine triggers, adequate sleep hygiene, good hydration, and dietary 
regulation further support headache prevention (Meise et al., 2022). 
OnabotulinumtoxinA (BoNT-A) is an established prophylactic therapy for CM. 
Its proposed mechanism involves inhibition of peripheral nociceptive input and 
attenuation of central sensitization (Gazerani et al., 2006). The PREEMPT 
clinical trials demonstrated significant reductions in headache frequency and 
sustained improvement in quality of life following treatment with BoNT-A, 

 
2 
 
leading to regulatory approval of BoNT-A for CM prevention (Diener et al., 
2010; Aurora et al., 2011). 
Greater occipital nerve block (GONB) is another therapeutic approach used in 
chronic migraine and other headache disorders. By targeting the sensory 
innervation of the occipital region, GONB can provide rapid pain relief and 
short-term reduction in migraine burden (Diener et al., 2012). However, the 
duration of benefit is often limited to days or weeks, and standardized protocols 
remain lacking due to scarce high-quality randomized trials (Ashkenazi & 
Levin, 2007; Sun-Edelstein et al., 2016). 
Despite strong evidence supporting BoNT-A and emerging evidence for GONB 
in chronic migraine, no high-quality randomized controlled trials have directly 
compared combination therapy versus BoNT-A alone and GONB alone. 
Existing studies focus on each treatment independently, and the potential 
synergistic effect of the two therapeutic approaches remains insufficiently 
evaluated. This creates an important clinical gap regarding whether combination 
therapy offers superior benefit to monotherapy. 
Given the rapid but transient effect of GONB and the slower onset but sustained 
effect of BoNT-A, we hypothesize that combination therapy with BoNT-A and 
GONB will result in immediate and prolonged reduction in monthly migraine 
days and improved patient-reported outcomes compared with either BoNT-A 
alone or GONB alone. 
 
Aim of the work: 
The main objective of this study is to compare the efficacy, patient-reported 
outcomes, and safety of three therapeutic approaches for treatment of chronic 
migraine, Onabotulinumtoxin A (BoNT-A) combined with a greater occipital 
nerve block (GONB), BoNT-A monotherapy, and GONB monotherapy. 
 

 
3 
 
Patients and Methods 
Study design: 
This prospective, randomized, assessor-blinded, controlled trial will include 90 
patients diagnosed with chronic migraine. Participants will be randomly 
assigned to one of three treatment groups: Group 1 (n = 30) will receive BoNT-
A combined with GONB; Group 2 (n=30) will receive BoNT-A alone; and 
Group 3 (n = 30) will receive a GONB alone.  
Randomization will be performed using a computer-generated allocation 
sequence. Block randomization will be employed to ensure balanced allocation 
across the groups throughout the enrollment period. Randomization sequence 
will be generated by an independent investigator who is not involved in 
participant recruitment, clinical evaluation, intervention administration, or data 
analysis. Allocation concealment will be maintained using sequentially 
numbered, opaque, sealed envelopes (SNOSE), This procedure minimizes 
selection bias and preserves the integrity of the randomization process. 
Given the nature of the study, blinding of participants and treating clinicians is 
not feasible. However, to minimize detection bias, all outcome assessments will 
be performed by an independent investigator who will remain blinded to group 
allocation. In addition, the data analyst will be blinded to treatment assignments 
until completion of the primary statistical analysis, thereby preserving 
objectivity in data interpretation. 
The patients will be recruited from Neurology Clinic Beni-Suef University 
hospital during the period from January 2026 to January 2027.  
 
 
 
 
 

 
4 
 
Inclusion criteria: 
1. Diagnosis of chronic migraine according to the International 
Classification of Headache Disorders, 3rd edition (ICHD-3): headache 
occurring on ≥15 days per month for more than three months, with at 
least 8 days per month exhibiting migraine features. (International 
Headache Society, 2013) 
2. Age > 18 years 
3. Stable preventive migraine regimen for at least two months prior to 
recruitment 
Exclusion criteria: 
1. Co-morbid other 
2. Prior treatment with BoNT-A or GONB for headache within the previous 
3 months. 
3. Known hypersensitivity to BoNT-A or local anesthetics. 
4. Cervical anatomical abnormalities that hinder proper localization of 
injection sites or compromise the safety of the procedure 
5. Neuromuscular junction disorders (e.g., myasthenia gravis). 
6. Coagulation disorders or anticoagulant therapy that contraindicates nerve 
block. 
7. Significant psychiatric comorbidity that would impair proper pre and post 
treatment assessment. 
8. Pregnancy. 
 
Clinical assessment 
The patients will be subjected to a comprehensive headache assessment through 
face-to-face interviews with a neurologist who will be blinded to the type of 
intervention:  

 
5 
 
1) History taking focusing on: age, sex, disease duration, the presence of 
aura, allodynia, autonomic manifestations, and the current preventive 
migraine medications.  
2) Headache diary (at baseline and at one and three months after 
receiving treatment): It includes monthly migraine days (MMD) and 
monthly days with acute analgesics. 
3) The Arabic version of Headache Impact (HIT-6) (Hussein et al., 
2024): It will be performed for all included patients at baseline and at one 
and three months after receiving treatment. It is a six-item scale that 
assesses the impact of headache on daily activities, psychological well-
being, and social life, in addition to assessment of severity of pain, 
attention, and fatigue. Each item is rated using five responses (always, 
very often, sometimes, never, or rarely) (Kosinski et al., 2003). The total 
score ranges from 36 to 78, with higher scores indicating more severe 
headache (Gandek et al., 2003). 
 
4) The 12-item Allodynia Symptom Checklist (ASC-12): It will be 
performed for all included patients at baseline and at one and three 
months after receiving treatment. It is a validated instrument used to 
assess the presence and severity of cutaneous allodynia in patients with 
migraine. It includes 12 questions that evaluate the frequency with which 
patients experience pain or unpleasant sensations during everyday 
activities such as brushing hair, wearing glasses, resting the head on a 
pillow, exposure to heat or cold, or light touch. Each item is scored based 
on how often the symptom occurs, allowing calculation of a total score 
that classifies allodynia as absent, mild, moderate, or severe (Lipton et 
al., 2008). 
 

 
6 
 
5) The Migraine interictal burden scale (MIBS-4): It will be performed 
for all included patients at baseline and at one and three months after 
receiving treatment. It is a brief, validated tool designed to assess the 
burden experienced by patients between migraine attacks, capturing the 
often-overlooked interictal impact of the disorder. The scale evaluates 
four key domains: the effect of headaches on work or school 
performance, difficulties in planning or participating in social and leisure 
activities, the overall interference of migraine with daily life, and the 
emotional or affective toll experienced during headache-free intervals. 
Each of the four items is self-administered and scored based on frequency 
of impact, providing a clear and concise measure of interictal disability. 
The minimum score that can be obtained from the scale is 0, scores of 1–
2 indicate mild burden, scores of 3–4 indicate moderate burden, and 
scores above 5 indicate severe interictal burden (Buse et al., 2007).  
 
6) The patient’s global impression of change (PGIC): It will be 
performed for all included patients at one and three months after 
receiving treatment. It is a widely used, outcome measure that provides a 
holistic assessment of perceived improvement or deterioration following 
treatment. It consists of a single, straightforward question in which 
patients rate the overall change in their condition compared with a 
specified baseline. It captures multiple dimensions of health, including 
symptom severity, functional limitations, emotional well-being, and 
overall quality of life, making it a valuable complement to more domain-
specific scales. It is typically scored using a 7-point Likert scale, where 
patients rate the overall change in their condition compared with baseline. 
The response options range from ―very much improved‖ to ―very much 
worse‖ (Diener et al., 2019).  
 

 
7 
 
7) Short Assessment of Patient Satisfaction (SAPS) scale: It will be 
performed for all included patients at one and three months after 
receiving treatment. It consists of the following seven items: satisfaction 
with treatment, explanation of the treatment outcome, medical care, 
respect by the physician, participation in medical decision making, time 
with the physician, and satisfaction with clinic/ hospital care. Responses 
scales are 5-point scales. SAPS scores were interpreted as follows:  0 -10 
= very dissatisfied, 11 - 18 = dissatisfied, 19 - 26 = satisfied, and 27 - 28 
= very satisfied (Yellen et al., 2002). 
 
Interventions 
 Group (1): Combination therapy (BoNT-A + GONB) 
          BoNT-A:  
 Administered following the PREEMPT protocol for migraine (Aurora 
et al., 2010). 
 Total dose: 155–195 units, distributed across standard injection sites 
including the frontal, temporal, occipital, cervical, and trapezius 
regions. 
 Injection technique: Intramuscular, as per established PREEMPT 
guidelines. 
GONB: 
 Administered bilaterally immediately after BoNT-A injections at 
baseline. 
 Medication: Lidocaine 1% - 2%, 1- 2 mL per side. 
 Technique: Targeted infiltration at the greater occipital nerve region, 
ensuring accurate delivery while minimizing risk of local 
complications. 
 
 

 
8 
 
 Group (2): BoNT-A monotherapy 
BoNT-A injections as above (at baseline).  
 Group (3): GONB monotherapy 
Bilateral GONB with Lidocaine as above (at baseline).  
 
Outcome 
 Primary outcome 
1. Responder rate: Proportion of participants achieved a ≥50% reduction in 
MMDs at one and three months after receiving treatment. 
 Secondary outcomes 
1. Time to first clinically meaningful response: Duration until participants 
achieve 30% decrease in MMDs. This threshold aligns with established 
IMMPACT recommendations for defining clinically meaningful 
improvement in chronic pain and migraine trials (Dworkin et al., 2008). 
2. Changes in patient-reported outcomes: Differences from baseline in 
the total scores of HIT-6, ASC-12, and MIBS at one and three months 
after receiving treatment. 
3. Acute medication use: Variation in frequency and dosage of acute 
migraine treatments at one and three months after receiving treatment 
compared to baseline. 
4. Patient-perceived improvement: Assessment of overall improvement 
using PGIC and SAPS scales at one and three months after receiving 
treatment. 
5. Safety and tolerability: Incidence and severity of adverse events, both 
local and systemic. 
 
 
 

 
9 
 
Ethical considerations 
Written informed consent will be obtained from the participants. Data will be 
confidential and anonymous. Administrative approvals will be sought from the 
head of selected facilities. Ethical approval will be sought from ethics 
committee, faculty of medicine, Beni-Suef University.  
Sample Size 
The sample size for this randomized controlled trial was calculated using 
GPower. A one-way ANOVA (fixed effects, omnibus) was selected to compare 
the primary outcome across the three study groups. Using an effect size of f = 
0.335, a significance level of α = 0.05, and statistical power of 80%, with three 
parallel groups, the minimum required total sample size was 90 participants. 
This corresponds to 30 participants per group, as shown by the GPower output 
(noncentrality parameter λ = 10.10, numerator df = 2, denominator df = 87, 
actual power = 0.805). This sample size ensures adequate power to detect 
clinically meaningful differences between the intervention arms. 
 
 

 
10 
 
Statistical analysis 
IBM SPSS (Statistical Package of Social Science) Version 25 will be used to 
analyze the data. Kolmogorov–Smirnov test will be used to test the normality of 
data. Categorical variables will be expressed as numbers and percentages. Non-
normally distributed quantitative variables will be expressed as median and inter 
quartile range (IQR). Normally distributed quantitative variables will be 
expressed as mean and standard deviation. Chi-squared test will be used for 
comparison between groups in categorical variables. Independent sample t test 
will be used for comparison between quantitative normally distributed variables, 
whereas Mann- Whitney test will be used for comparison between quantitative 
non-normally distributed variables. Correlations between quantitative variables 
will be done using Spearman or Pearson correlation test. P-value ≤0.05 was 
considered statistically significant. All tests will be two-tailed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
11 
 
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