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REVIEW ARTICLE
Year : 2021  |  Volume : 69  |  Issue : 7  |  Page : 228-256

Role of Greater Occipital Nerve Block in Headache Disorders: A Narrative Review


Department of Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi, India

Date of Submission01-Mar-2021
Date of Decision01-Mar-2021
Date of Acceptance02-Mar-2021
Date of Web Publication14-May-2021

Correspondence Address:
Debashish Chowdhury
Professor, Department of Neurology, GB Pant Institute of Post Graduate Medical Education and Research, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.315993

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 » Abstract 


Background: The proximity of sensory neurons in the upper cervical spinal cord to the trigeminal nucleus caudalis (TNC) neurons and the convergence of sensory input to TNC neurons from both cervical and trigeminal fibers underscore the rationale of using greater occipital nerve block (GON-block) for acute and preventive treatment in various headache disorders.
Objective: The aim of this study was to critically review the existing literature regarding the safety and efficacy of GON-block in various headache disorders.
Methods: We searched the eligible studies in English by searching in PubMed till December 31, 2020 for randomized controlled trials (RCTs), observational studies, open-label studies, case series, and case reports on the efficacy and the safety of GON-block for the treatment of headache disorders using the keywords “greater occipital nerve block”, “headache” and “treatment”. Studies using combination of GON-block and other peripheral nerve blocks (PNBs) and C2/C3 blocks were excluded.
Results: Seventy-two eligible studies were reviewed. Based on RCTs and open-label studies, good evidence of the efficacy of GON-block was found for migraine, cluster headache (CH), post-dural puncture headache (PDPH), cervicogenic headache (CGH), and occipital neuralgia (ON). The analgesic effect of GON-block outlasted its anesthetic effect by days to weeks. Evidence for acute and short-term (transitional) treatment was more robust than for long-term prevention. GON-block was found to be safe and the treatment-emergent adverse effects (TEAEs) were generally mild and transient.
Conclusion: GON-block is a useful modality of treatment in various headache disorders because of many attractive features such as its early effect in reducing the severity of pain, sustained effect following a single injection, easy technique, minimum invasiveness, minimum TEAE, no drug-to-drug interactions, and negligible cost.


Keywords: Acute treatment, efficacy, greater occipital nerve block, headache, preventive treatment, safety
Key Messages: Our review found that the greater occipital nerve block (GON-block) is an efficacious and safe treatment option in various headache disorders such as migraine, CH, PDPH, CGH, and ON. Its role in other headache disorders is still anecdotal and needs further trials.


How to cite this article:
Chowdhury D, Datta D, Mundra A. Role of Greater Occipital Nerve Block in Headache Disorders: A Narrative Review. Neurol India 2021;69, Suppl S1:228-56

How to cite this URL:
Chowdhury D, Datta D, Mundra A. Role of Greater Occipital Nerve Block in Headache Disorders: A Narrative Review. Neurol India [serial online] 2021 [cited 2021 Jun 16];69, Suppl S1:228-56. Available from: https://www.neurologyindia.com/text.asp?2021/69/7/228/316090




In the last two decades, greater occipital nerve block (GON-block) has emerged as an alternative treatment option for many primary and secondary headache disorders.[1],[2] GON is the principal sensory nerve innervating the occipital area. It derives most of its fibers from the cervical (C2) dorsal root. The convergence of sensory neurons of C2 in the upper cervical spinal cord and the neurons of the trigeminal nucleus caudalis (TNC) provides the rationale for using GON-block for acute and preventive treatment in various headache disorders.[3],[4] GON-block targets the anatomical and the functional continuum between trigeminal and cervical fibers in the so-called trigemino-cervical complex (TCC).[5] It is believed to modulate the excitability of second-order neurons receiving input from both trigeminal and cervical afferents when either of them is stimulated.[6],[7] Additional advantages of GON-block include safety, low cost, easy technique, and little potential for the drug to drug interactions.[8] In this review, we shall critically examine the role of GON-block as a treatment option for various headache disorders.


 » Materials and Methods Top


We identified potentially eligible studies by searching in PubMed till December 31, 2020 for randomized controlled trials (RCTs), observational studies, open-label studies, case series, and case reports on the efficacy and the safety of GON-block for the treatment of headache disorders in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The keywords used were “greater occipital nerve block”, “headache” and “treatment”. The search terms were used as keywords and in combination as MeSH terms to maximize the output from literature findings. Only the studies published in English were included. Studies that assessed only the GON-block (with or without trigger point injections) were included whereas the studies that used GON-block with other peripheral nerve blocks (PNBs) or C2/C3 blocks were excluded from this review.


 » Results Top


PRISMA flowchart is shown in [Figure 1]. All the three authors independently read the titles and the abstracts and excluded from the analysis the articles which did not pertain to the efficacy and safety of the GON-block in headache disorders. Of a total of 226 articles, 72 were included in this review.
Figure 1: PRISMA flow diagram showing the progression of article selection and the numbers of articles at each step

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Evidence of the efficacy for migraine

RCTs

Ashkenazi et al.[9] compared GON-block with or without steroid (triamcinolone) in 37 patients of transformed migraine. Twenty minutes after the injection, mean headache severity decreased significantly in both the groups from baseline but did not differ significantly between the two groups. Similarly at 4 weeks, the number of headache-free days and analgesic consumption improved from baseline but did not differ significantly between the two groups.

Kashipazha et al.[10] using a similar design performed GON-block bilaterally once every month for two months in 52 patients. In both the active and placebo groups, pain severity, pain frequency, and analgesic use were significantly lower than pre-treatment (P < 0.001) at 2, 4, and 8 weeks after the intervention. However, no difference was observed in the outcome between the two groups.

Inan et al.[11] administered GON-block with bupivacaine versus saline once per week for four times in chronic migraine (CM) patients (42 in each group); thereafter blinding was removed and both groups received GON-block with bupivacaine, administered once a month for 2 months. After 1 month, the number of headache days and headache severity decreased significantly in the bupivacaine group. After changing the placebo group with bupivacaine, both the groups showed a similar significant decrease in headache days and headache severity in the second and third months.

Palamar et al.[12] studied ultrasound-guided unilateral GON-block (bupivacaine versus saline injection) in 23 patients of refractory CM. Visual analog scale (VAS) scores on the ipsilateral side of injection showed a significant decrease in the active arm when compared to baseline (within the group comparison). However, when compared between the groups (active versus placebo), the VAS scores did not differ. There was no change when VAS scores were analyzed for the side that did not receive the injections.

Dilli et al.[13] studied the efficacy of single bilateral or unilateral GON-block in 63 migraine patients [both episodic migraine (EM) and CM]. The active group received GON-block with local anesthetic (LA) and methylprednisolone (MPS) and the placebo group received 0.25 mL 1% lidocaine (to create numbness over the GON dermatomal region) and saline. The frequency of moderate or severe headache (primary outcome) showed at least 50% reduction in 30% of patients for both the groups at 1 month. Secondary outcome measures also did not show any difference between the groups.

Cuadrado et al.[14] studied the short term efficacy of a single injection of bilateral GON-block (bupivacaine versus saline injection) in 36 women with CM. They also analyzed the effect of the GON-block on pressure pain thresholds (PPTs) at different territories. The assessments were done at 1 h and 1 week after the GON-block showed a significant absolute reduction in mean frequency of moderate or severe headache days and the reduction of any intensity headache days in the active group as compared to placebo. The proportion of patients showing ≥50% reduction in moderate or severe headache days was also higher in the active group. Overall, PPTs increased after the LA blockade and decreased after the placebo.

Gul et al.[15] assessed 44 patients of CM once per month for 3 months following GON-block. The mean number of headache days and VAS scores were significantly lower as compared to pretreatment in the active group at the first, second, and third months, whereas in the control group, they became non-significant after the second and third months.

Friedman et al.[16] analyzed the effects of bilateral GON-block in 28 patients (13 in the active and 15 in the sham group) with acute migraine. Complete headache freedom at 30 min after the procedure, higher frequency of sustained pain relief (no requirement of additional medication) and a significant improvement of pain score was observed in patients with the GON-block but none in the sham group.

Flamer et al.[17] used USG-guided GON-block in 40 patients with CM one time, either unilaterally or bilaterally depending on the laterality of headache. GON-blocks were given over the distal site (at the level of the superior nuchal line 2–3 cm lateral to the external occipital protuberance) in 20 patients and at the proximal site (between the spinous process of C2 and the transverse process of the C1) in 20 patients. Short term effects in terms of reduction of numerical rating scale (NRS) pain score at 24 h and 1 week were observed in both proximal as well as distal groups. However, the longer reduction in NRS score at 1 and 3 months was seen in the proximal group only. Significant reduction of headache days per week at 1 month and improvement of sleep interruption at 1 week were also observed in both the groups.

Friedman et al.[18] in a randomized, double-dummy study used GON-block with 6 mL of 0.5% bupivacaine and intravenous (IV) physiological saline in one group versus sham GON-block with 6 mL of normal saline and IV metoclopramide (10 mg) infusion in the other during an acute migraine attack in the emergency department. Of 99 patients, 51 patients received GON-block and 48 patients received metoclopramide. Mean improvement of pain (0–10 pain scale) at 2 h after the injection was 5 and 6.1 in GON-block group and metoclopramide group, respectively. Sustained headache relief and headache freedom at 48 h after injections were observed in 28% and 6%, respectively, in the GON-block group and 38% and 15%, respectively, in metoclopramide group. Thirty-three percent of patients in the GON-block group and 17% in the metoclopramide group required rescue medication in the emergency following the injections.

Open-label studies

Young et al.[19] in a 47-year-old woman of CM with brush allodynia used unilateral GON-block and bilateral tender point injections at C2 and left C5 paraspinal and trapezius muscles and observed complete resolution of allodynia and pain at 5 min after the injections.

Ashkenazi et al.[20] used GON-block along with trigger point injections in 19 patients of episodic or transformed migraine with brush allodynia and assessment was done at 20 min after the block. Of 19 patients, 4 patients received only GON-block (LA and steroids), and the remaining 15 patients along with GON-block also received trigger point injections (LA). The pain was reduced in 17 patients (89.5%) after 20 min of the injections. Similarly, a significant reduction of allodynia over the trigeminal area and in the cervical area was observed after the injections.

Rozen et al.[21] observed a dramatic response of complete disappearance of headache and neurological symptoms after bilateral GON-block in two patients of hemiplegic migraine.

Takmaz et al.[22] prospectively used GON-block in 10 women suffering from migraine. Patients were given three GON-blocks at weekly intervals and thereafter repeated if required for a maximum of five sessions. A total of 74 injections were performed. Patients responded in terms of reduction in total pain score, migraine attacks, and mean analgesic consumption up to 6 months.

Young et al.[23] used GON-block with LA in 25 patients of EM or CM with brush allodynia over trigeminal distribution and assessment was done at 5 min and 1 week after the block. Improvement of average scores of headache intensity by 64%, allodynia by 75%, and photophobia by 67% was observed after 5 min of the block. Allodynia was improved significantly faster than pain and the mean duration of benefit noted after the block was 4 days.

Weibelt et al. [24]studied 150 patients of CM of which 37 received unilateral and 113 received bilateral GON-block. Fifty-two percent of patients experienced ≥50% reduction in headache days, 54% experienced ≥50% reduction in functionally incapacitating headache days and 60% reported their headaches 'much better' or 'better' at 1 month compared to baseline. No influence of medication overuse headache (MOH) on the likelihood of treatment response was seen.

Baron et al.[25] used unilateral GON-block in a 45-year-old woman with basilar-type migraine. Complete resolution of headache, photo, and phonophobia, visual disturbances, nausea, imbalance, and speech symptoms were observed within several minutes after the block.

Casas-Limon et al.[26] observed dramatic improvement of hemiplegic aura symptom along with headache within 50 min after bilateral GON-block with LA in a 26 years woman of migraine.

Inan et al.[27] assessed 78 migraine patients and compared those who received GON-block with medical prophylaxis and those without. GON-block was applied weekly in the first month and then monthly for 2 months. Headache attack frequency, duration, and severity decreased significantly from the baseline in both the groups but there was no significant difference between the groups at the third month.

Okmen et al.[28] treated 60 migraine patients with GON-block four times weekly for one month. VAS and the number of attacks were lower in the following 6 months compared to prior values statistically. MIDAS scores were lower in the third and sixth months compared to baseline values.

Kocer et al.[29] used GON-block once a month for 3 months bilaterally in 9 cases of refractory CM (defined as nonresponsive to three preventive drugs in adequate doses for 3 months each for a total duration of at least1 year). Eight of nine patients reported a marked decrease in frequency and severity of migraine attacks and improvement in MIDAS as compared to baseline.

Cuadrado et al.[30] used GON-block in 18 patients of migraine with prolonged or persistent aura. Of 22 auras that were treated, 19 auras (86.4%) responded to GON-block. Complete response was more common in cases with prolonged auras lasting <1 week than in those with persistent auras.

Safiabadi et al.[31] treated 16 patients of CM with unilateral GON-block. The assessments done at 2 weekly intervals for 6 weeks showed significantly decreased headache frequency (all three fortnights) and headache severity (in the first and second fortnight only) but not headache duration as compared to baseline.

Unal-Artık et al.[32] retrospectively compared unilateral versus bilateral GON-block in 23 and 18 patients of CM, respectively. GON-blocks were performed weekly for 4 weeks followed by monthly injections for 2 months. Headache days, duration, and VAS did not show any difference between the two groups.

Allen et al.[33] analyzed the efficacy of GON-block in 562 migraine patients. GON-blocks were given either with bupivacaine (0.25%/0.5%) or lidocaine (1%). Repeated GON-blocks were given in 334 patients and the response was noted after 1 to 4 weeks. Significant, moderate, and minimal responses were seen in 58%, 23% and 18.5% of patients, respectively. Patients with repeated GON-blocks had a greater response than those with a single GON-block.

Vigano et al.[34] studied neurophysiological correlates of clinical improvement after GON-block in 17 CM patients (12 with MOH). There was a decrease in monthly headache days by 35%. Eight CM patients reverted to EM and MOH resolved in 11 of 12 patients. The neurophysiological correlates like visual evoked potential habituation and intensity dependence of auditory evoked potential improved after GON-block when compared to 19 healthy controls.

Ulusoy et al.[35] studied 84 patients with CM by using GON-block weekly for 3 weeks, and then monthly for 2 months. The VAS and HIT-6 (headache impact test-6) scores, headache attack frequency, headache days per month, nights awaken with headaches, the number of emergency visits, the duration of attacks, and MIDAS scores were significantly reduced after GON-block compared to pre-treatment values. Anxiety, depression, and the sleep quality index were also improved with GON-block. Studies documenting the evidence of efficacy of GON-block in migraine are summarized in [Table 1].
Table 1: RCTs and open-label studies on the efficacy and safety of GON-block in migraine

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Evidence of the efficacy for tension-type headache (TTH)

Open-label study

Leinisch-Dahlke et al.[36] did not find a positive response after GON-block with LA and steroid over 2 weeks follow-up in 11 (73%) of 15 patients of chronic TTH (CTTH). In fact, headaches were exacerbated in 4 (27%) patients [Table 2].
Table 2: RCTs and open-label studies on Efficacy and safety of GON-block in trigeminal autonomic cephalalgias and other primary headaches

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Evidence of the efficacy for trigeminal autonomic cephalalgias (TACs)

Cluster headache (CH)

RCTs

Ambrosini et al.[37] used GON-block in 13 patients of CH [episodic cluster headache (ECH)-9 and chronic cluster headache (CCH)-4] with LA & steroids versus 10 patients of CH (ECH-7 and CCH-3) with LA & physiological saline. Significant improvement was found after 4 weeks in the verum-group compared to the placebo group. Eleven patients (85%) became attack free within the first week after the GON-block (none in the placebo). Among the responders, 8 patients remained attack-free for 4 weeks.

Leroux et al.[38] administered GON-block in 21 patients of CH (ECH-14 and CCH-7) with steroids (cortivazole; 3.75 mg in 1.5 mL) versus placebo in 22 patients of CH (ECH-14, CCH-8). GON-block was given 2–3 times over a period of 90 days. Twenty patients of 21 in the steroid-group had a mean of ≤2 daily attacks after GON-block as compared to only 12 of 22 placebo-group (P = 0.012) and fewer mean attacks in the first 15 days after the block as compared to the placebo-group (P = 0.004).

Open-label studies

Peres et al.[39] used GON-block (lidocaine and triamcinolone) in 14 patients with ECH and CCH. One week after the GON-block, 67% of ECH and 60% of CCH patients showed a reduction in the duration (48.5 ± 17.3 min vs 23.9 ± 26.3 min), attack frequency (3.1 ± 1.4 vs. 1.1 ± 1.3), and attack intensity (9.1 ± 1.2 vs 4.3 ± 4.2). The mean number of headache-free days after the blockade was 13.1 days.

Busch et al.[40] prospectively studied 15 patients with CCH using only prilocaine. Three patients did not have an attack on the day of the block, 3 patients till next day, 1 patient till next 3 days. One patient had fewer intensive attacks for 1 week and 1 patient did not have autonomic symptoms for 3 days. There was, however, no change in headache attack frequency after 1 week of the block.

Gantenbein et al.[41] found a complete response in 63% of patients of ECH (n = 31) and 29.9% patients of CCH (n = 29) and the duration of effect after a single GON-block lasted for a median of 25 and 14 days in ECH and CCH groups, respectively.

Lambru et al.[42] prospectively studied 83 patients of CCH and found a positive response of GON-block in 47 (57%) patients that lasted for a median of 21 days (range 7–504 days).

Rozen et al.[43] in a cross-sectional observational study found a positive response of GON-block in 9/10 patients of treatment-refractory CCH.

Gonen et al.[44] in a retrospective study found a significant reduction of attack duration during the first 28 days after a single GON-block in 51 patients of ECH and CCH. In 28 (54.9%) patients, there were no attack or cluster bouts after a single GON-block.

Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing (SUNCT)

Porta-Ertesam et al.[45] observed complete remission of headache for 48 h after the GON-block in a patient of SUNCT and improvement of headache attacks persisted for nearly 3 weeks. Studies documenting the evidence of efficacy of GON-block in TACs are summarized in [Table 2].

Evidence of the efficacy for other uncommon primary headaches and neuralgias and craniofacial pain syndromes

Orgasmic headache

Selekler et al.[46] found excellent response in a patient with an orgasmic headache after a single GON-block. The patient reported no orgasmic headache from 4th day i.e., first day of intercourse after the GON-block till the end of follow-up at the 10th week.

Hypnic headache

Rehmann et al.[47] noted a positive response after 2 GON-blocks with an interval of 2 weeks in a patient with hypnic headache.

Occipital neuralgia (ON)

Vanderhoek et al.[48] used GON-block in 1 patient and GON-block with radiofrequency ablation in another patient of ON. Both the patients responded immediately after the intervention and the benefit persisted for several months in 2nd patient.

Kastler et al.[49] in a retrospective study analyzed the effect of CT-guided GON-block in 33 patients of ON. The block was performed over the first bend of the GON between the inferior obliqus capitis and semispinalis capitis muscles. Pain reduction >50% was observed in 86.5% of the procedures. The mean pain relief duration was 9.15 months (range 3–24). Excellent results (above 75% pain decrease) were obtained in 62.5%. Acute pain medication could be discontinued in 15 patients (54%) and decreased in 6 patients (21%).

Trigeminal neuropathy

Weatherall et al.[50] used GON-block in a 69-year-old woman with idiopathic trigeminal neuropathy. GON-blocks were given twice at an interval of 8 weeks. At 8 weeks, her facial sensory disturbances became less severe and less extensive and after 3 months of 2nd block, although no further improvement was noted, symptoms stabilized. Studies documenting the evidence of efficacy of GON-block in other primary headaches are summarized in [Table 2].

Evidence of the efficacy for secondary headaches

Cervicogenic headache (CGH)

RCT

Lauretti et al.[51] in a randomized double-blind study used GON-block in 30 patients of refractory cervicogenic headache (CGH) first by classic technique and subsequently by suboccipital compartment technique. Patients were divided into 3 groups: group 5-first received GON-block with 5 mL infiltrate by classic technique and then with 5 mL infiltrate by suboccipital technique, group 10- first received GON-block with 5 mL infiltrate by classic technique and then with 10 mL infiltrate by suboccipital technique and group 15-first received GON-block with 5 mL infiltrate by classic technique and then with 15 mL infiltrate by suboccipital technique. Significant decrease in pain intensity (VAS) was observed in all patients of sub-occipital compartment technique and persisted for 24 weeks whereas for only 2 weeks in classic technique. Similarly, a significant reduction in analgesic consumption was achieved for 2 weeks after GON-block by classic technique as compared to 24 weeks after GON-block by sub-occipital compartment technique.

Open-label studies

Vincent et al.[52] et al. noted a significant reduction of headache intensity in patients with CGH immediately after the GON-block and the response persisted for 2 weeks after the block.

Hecht et al.[53] noted good response after the GON-block in 80% of the 10 patients with post-concussive CGH.

Arman et al.[54] in a retrospective study analyzed the effects of GON-block or C2/C3 facet joints block in 58 patients of CGH. Twenty-nine patients were distributed in each group. Response in terms of >50% reduction of pain was observed in 62.5% and 50.5% in C2/C3 group and GON-block group, respectively. Significant reduction of pain (NRS) at 1 week and 1 month after treatment was observed in both the groups as compared to baseline. The pain reduction (frequency) one week after blocking in C2/C3 group was significantly more than the GON-block group (53.79 ± 19.71 vs 67.58 ± 23.85, P = 0.02).

Ertem et al.[55] noted a significant reduction in headache intensity after 3 GON-blocks over 3 months in 21 patients of CGH.

Rothbart et al.[56] reported a patient with CGH and coexisting hemicrania continua (HC) who had a quick relief within 10 min after using GON-block that persisted up to 2 months.

Post dural puncture headache (PDPH)

Open-label studies

Matute et al.[57] showed complete resolution of headache after GON-block in 2 patients (100%) of PDPH

Akin Takmaz et al.[58] observed dramatic improvement of headache after GON-block in a 29 year-old man with PDPH with complete resolution of pain within 2 min after the block. Although a milder intensity pain recurred after 12 h, it disappeared completely after a repeat block.

Niraj et al.[59] noted that in 18 patients of PDPH, a single GON-block relieved not only the postural headache but also the photophobia, nausea, and neck stiffness and these effects persisted for 6 weeks.

Akyol et al.[60] found a significant reduction in headache intensity within 24 h after GON-block in PDPH patients. However, the effect was sustained beyond 24 h only in patients with relatively milder intensity with pre-block VAS score between 4 and 6.

Uyar Turkyilmaz et al.[61] in a retrospective study noted significant improvement in headache intensity at 10 min, 2 h, and 24 h after a single GON-block in 16 patients with PDPH.

Medication overuse headache

Karadas et al.[62] used GON-block in 105 patients with a triptan overuse headache and not taking prophylactic medications. The patients were divided equally into 3 groups: group 1––abrupt withdrawn of triptan and no GON-block, group 2––abrupt withdrawn of triptan and single GON-block and group 3––abrupt withdrawn of triptan and weekly three-stage GON-block. GON-block was given with lidocaine and the patients were followed at second and fourth month after the GON-block. Significant reduction of the number of headache days, triptan intake, and headache intensity at second and fourth month was noted in group 3 as compared to group 1 but not between group 1 and group 2. Similarly, a significant reduction in the number of headache days, triptan intake and headache intensity at fourth month was noted in group 3 as compared to group 2.

Secondary SUNCT

Choi et al.[63] found a positive response after GON-block in a patient with atypical SUNCT following whiplash injury. The patient reported no more pain, lacrimation, or conjunctival injection after the three blocks given at one weekly interval.

Post traumatic headache (PTH)

Seeger et al.[64] studied 15 pediatric patients of PTH (14 completed the follow-up). Nine participants received a single GON-block, 4 had a second block, and 1 received a total of five blocks. Nine participants had a full response, 1 had a partial response and the remaining four had no improvement.

Spontaneous intracranial hypotension

Niraj et al.[65] et al. found a positive response after bilateral GON-block in a patient of spontaneous intracranial hypertension (SIH). The positive response was sustained for a period of 5 months after a single block. Studies documenting the evidence of efficacy of GON-block in secondary headaches are summarized in [Table 3].
Table 3: RCTs and open-label studies on the efficacy and safety of GON-block in secondary headaches

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Evidence of the efficacy of GON-block for a mixed population of headache disorders

RCT

Terzi et al.[66] used GON-block in 20 patients each of migraine, TTH and CGH. Each group was divided equally into active and placebo arms. The assessment was done at 5 10 and 30 min. Significant reduction of pain over the orbitonuchal (ONC) and the orbitofrontal area was noted in CGH after GON-block as compared to placebo whereas in migraine and TTH patients, the pain reduction occurred only in the ONC area.

Ryu et al.[67] used USG-guided GON-block in 54 patients of primary headache of varied etiology (TTH 25, migraine12, cluster 9 and new daily persistent headache8). They were divided into 2 groups and given either GON-block (1 mL levobupivacaine (0.1%) and 1 mg dexamethasone) or 1 mL of 50 units botulinum toxin type A. Reduction of VAS score at 1 week after the intervention was observed in both the groups but was significantly lower in the botulinum toxin group at 4, 8, and 24 weeks.

Open-label studies

Saadah and Taylor[68] studied 112 patients with treatment-refractory severe headaches who received 118 injections on separate headache episodes (unclassifiable: 7%, vascular: 31%, tension: 45%, post-infection: 11% and post traumatic: 6%). Relief of headache was observed in 62% of unclassifiable headache, 97% of vascular headache, 96% of tension headache, 75% of post-infection headache and 100% of post-traumatic headache. Sustained relief longer than 1 week was achieved in 65%.

Anthony et al.[69] used GON-block first with LA only and then with steroid only in 50 patients each of migraine and ON. Immediate relief of headache after the first block (LA only) was noted in 84% and 88% of patients of ON and migraine, respectively. The headache returned within 4 to 24 h in 20 patients of ON and within 3 h to 3 days in 20 patients of migraine. After the second block (steroid only), 88% of 50 patients with migraine became headache-free with a mean duration of 32 days (10–66 days) and 87% of 86 patients with ON became headache-free with a mean duration of 31 days (16-144 days).

Afridi et al.[70] studied 101 patients with CDH (54 migraine, 19 CH, 7 HC, 10 new daily persistent headache (NDPH), and 11 other headaches). A complete (pain-free) and partial response was seen in 9 and 17 patients, respectively, with migraine and 10 and 3 patients, respectively, with CH. The mean duration of complete and partial response after a single GON-block was 9 days and 61 days, respectively, in migraine and 17 days and 52 days, respectively, in CH. Tenderness over the GON, not the local anesthesia after the injection was found to be strongly predictive of outcome. Four of 10 patients with NDPH, 1 of 7 with HC, 1 of 1 with chronic paroxysmal hemicrania (CPH), and SUNCT showed complete response whereas partial response was noted in 5 patients with HC, 6 with NDPH, 2 with CGH, 2 with post-traumatic headache (PTH), and 1 patient with low CSF pressure headache.

Tobin et al.[71] studied the effects of repeated GON-blocks in primary and secondary headache disorders. Total 121 patients were included in the study and follow-up data were available for 108 patients (migraine: 57, ON: 35, Post-concussive headache: 12, CH: 2, non-ON: 2). Overall, 83 patients (77%) responded to GON-block with a mean benefit duration of 6.6 ± 6.1 weeks. Migraineurs with symptomatic MOH were associated with an increased risk of GOB-block failure than those with ON.

Na et al.[72] used GON-block in 26 patients of CGH and ON either by USG guidance (n = 13) or blindly (n = 13) and the response was noted immediately. The success rate in achieving complete block was higher in USG-guided group as compared to the blind procedure.

Shim et al.[73] used GON-block in 31 patients of CGH and 14 of ON. The GON-block was given either USG guidance (n = 22) or blindly (n = 20). Significant reduction of headache intensity was observed in both the groups at 1 week. Although the response persisted at 4 weeks in both the groups, a more sustained benefit was observed in the USG-guided block group as compared to the blind block group.

Jurgens et al.[74] in a retrospective chart review analyzed the response of occipital nerve block in 20 patients with craniofacial pain syndrome. Of 20 patients, 8 were trigeminal neuralgia, 6 were trigeminal neuropathic pain, 5 were persistent idiopathic facial pain and 1 was ON. A total of 25 occipital nerve blocks were given and the response rate of the blocks was 52%. Eleven patients (55%) showed a positive response with a global improvement of at least 50% pain from baseline. The response rate was highest in ON (100%) followed by trigeminal neuralgia (75%). The effects lasted for an average of 27 days.

Gelfand et al.[75] studied 46 children (<18 years) (migraine: 35, NDPH: 9 and chronic undifferentiated TAC: 2) and 40 completed the follow-up. Overall, 53% benefitted from GON-block and significant benefit was seen in 28%. Mean latency for the onset of benefit and mean duration of benefit was 4.7 days and 5.4 weeks, respectively. Sixty-two percent of migraine patient and 32% of NDPH patients benefitted after single GON-block.

Kim et al.[76] in a retrospective chart review noted the response after GON-block in 10 migraine and 3 ON patients. Headache intensity significantly decreased after the block with a mean duration of relief of 148.05 days.

Zifpel et al.[77] in a retrospective study used USG-guided GON-block with LA and steroid in 12 patients of refractory occipital neuralgia or craniofacial pain syndrome of varied etiology. A total of 21 infiltrations were given either unilaterally or bilaterally. The blocks were effective in 93.4% of the patients as determined by immediate post-block headache intensity reduction (>50% decrease of VAS score). Clinical efficacy in terms of reduction of pain intensity (VAS) at 1 week, 1 month, and 3 months was achieved in 80%, 66.7%, and 60%, respectively.

Pingree et al.[78] used USG-guided GON-block with LA and steroid in 14 patients with occipital neuralgia or CGH. GON-block was successful in 12 patients (86%) as determined by the absence of light-touch sensation in the dermatomal distribution at 30 min after the block. Significant decrease in pain score (NRS) at 4 weeks after the block was achieved as compared to baseline.

Kastler et al.[79] used MRI-guided GON-block with LA and steroid in 9 patients of refractory craniofacial pain syndrome with occipital tenderness and 2 of CH. Of 16 of total GON infiltrations, clinical success in terms of headache intensity reduction (>50% decrease of VAS score) was achieved in 7 patients (63.6%) with a mean self-reported improvement of 78%.

Puledda et al.[80] treated 159 children and adolescents with disabling headaches with GOB-block (79% had CM, 14% NDPH, 4% TACs, 3% secondary headache and one patient CTTH). Improvement was seen in 68% of patients with CM, 67% with TACs, and 59% with NDPH lasting on average for 9 ± 4 weeks. Studies documenting the evidence of efficacy of GON-block in a mixed population of headache disorders are summarized in [Table 4].
Table 4: RCTs and open-label studies on the efficacy and safety of GON-block done in a mixed population of headache disorders

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Adverse effects of GON-block

Overall, GON-block use in headache disorders has been found to be very safe. Most of the RCTs as well as open-label studies did not find any serious TEAE. Of 72 studies reviewed, TEAE were reported only in a few studies (8 RCTs in migraine,[11],[12],[13],[14],[15],[16],[17],[18] 2RCT in CH,[37],[38] 1 RCT in CGH[51] and 21 open-label studies). Majority of the TEAE were mild and transient. The commonly reported TEAE in RCTs were neck pain, dizziness, injection site pain, and vertigo [Table 5]. Other TEAE reported in open-label studies[22],[24],[32],[33],[36],[41],[42],[43],[44],[49],[54],[55],[64],[68],[70],[72],[74],[75],[77],[79],[80] included vasovagal syncope, presyncope, tenderness at injection site temporary numbness at the injection site, transient neck pain, transient dizziness or lightheadedness, redness in the injection site, burning at the injection site, facial edema, sleep disturbances, steroid acne, oral candidiasis, transient bradycardia, palpitation, neck stiffness, mild occipital neuralgia, transient neck torticollis, minor bleeding from the injection site, initial worsening of migraine, transient hypophonia and dysphagia, local site soreness, transient tingling/numbness in the distribution of injected nerve immediately after the injection, allergic reaction, local hematoma, redness at the injection site, nausea, pseudoseizure, and headache. Rozen et al.[43] found that one patient with CH developed unilateral avascular necrosis after receiving 30 injections and two others developed mild occipital neuralgia. One patient with PTH developed alopecia (1.5 × 1.5 cm) which resolved completely in 1 month.[64]
Table 5: Comparison of adverse effects between active and placebo/active comparator group in the RCTs using GON-block in headache disorders*

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 » Discussion Top


Our review found that GON-block can be an effective and well-tolerated treatment option for various primary and secondary headache disorders. Few reviews on the effectiveness of GON-block in various headache disorders have been published in the past.[1],[81],[82],[83],[84],[85],[86],[87],[88],[89],[90],[91],[92],[93] Our review further expands that literature based on many recently published studies and critically analyzes the role of GON-block in various headache disorders. Before analyzing the available evidence, we will present a brief historical background of the use of GON-block in headache disorders.

Brief Historical background: The story of occipital nerve blocks started with the recognition of ON as a clinical entity. Way back in 1821, Beruto et al.,[94] described ON as a sharp, lightning-bolt pain radiating from the occiput to the vertex. William Osler's textbook mentions the “tender occipital nerve zones” and mentions entities like cervico-occipital and occipito-cervical neuralgias.[95] Since the 1930s, astute clinicians started recognizing that occipital zone tenderness occurs commonly in various headache disorders and that these can be alleviated by occipital zone injections.[96],[97] Penfield in 1932 observed that by sectioning the internal half of the trigeminal root at the point where the extracranial sensory fibers (of the scalp) and the intracranial fibers (meningeal) of the upper part of the head meet, intractable headache in some patients can be cured.[98] By the 1960s, C2-C3 root or occipital nerve zone blocks with LA or a LA plus corticosteroid were being widely used as a medical therapy of ON.[99],[100],[101] Based on these premises, Sadaah and Taylor in 1978 treated a 45-year-old woman with a chronic and unresponsive headache that evolved from common migraine with occipital zone injections and found a favorable response.[68] In 1987, they reported their favorable experience of using occipital zone injections in 112 patients with “sustained headaches” of various aetiologies.[68] By 2000, GON-block was being widely used in various headache disorders.[102] A randomized trial in patients of “transformed migraine” was conducted in 2007 to see if the addition of steroid (triamcinolone) to the anesthetic agent in the block improves the outcome.[9] The first expert opinion on the use of GON-block in headache disorders[1] was published in 2008 followed by expert consensus recommendation of the American Headache Society Special Interest Section for PNBs and other Interventional Procedures (AHS-IPS) in 2013.[83]

Migraine: Ten RCTs and 13 open-label studies and 4 case reports were reviewed. GON-block was used in migraine as an acute treatment, in migraine with aura, in children with migraine, in high-frequency unresponsive migraine, and in CM patients as a short-term and long-term preventive. There was significant heterogeneity amongst the studies in terms of the study design, the methodology of GOB-block, and the outcome measures.

GON-block was found to be useful in alleviating pain and allodynia within 5 to 20 min in migraine.[19],[20],[23] One RCT in transformed migraine observed immediate response after GON-block within 20 min.[9] One RCT in acute migraine found that GON-block was superior to placebo in terms of achieving headache freedom at 30 min and improvement of pain score at 60 min after the injection.[16] Another RCT showed a robust response at 1 hour.[14] Similarly, three case reports also observed prompt and excellent recovery of neurological symptoms after GON-block in patients of hemiplegic migraine[21],[26] and 1 patient of basilar type migraine.[25] One open-label study found a promising response of aura symptoms after GON-block in migraine patients with prolong or persistent aura.[30] A recent RCT however found that injection GON-block was not as efficacious as IV metoclopramide for the acute treatment of migraine in the emergency department.[18]

Based on the results of the 4 RCTs,[11],[12],[14],[15] that studied the role of GON-block exclusively in CM patients, GON-block was found to be superior to placebo and well-tolerated.[8] One RCT[14] showed short term (1-week post-GON-block) improvement, two RCTs at 1 month[11] and 3 months[15] after the block, whereas the fourth RCT[12] observed reduction of severity, frequency, and analgesic use at 2, 4, and 8 weeks after the single GON-block in migraine patients as compared to baseline. Two retrospective studies also observed a good response after GON-block for at least 1 month in pediatric patients of CM.[75],[80] Only 1 RCTs[13] did not find any significant difference between GON-block and placebo (in terms of headache frequency reduction in patients with migraine). It is possible that the difference could not be detected because of the use of 0.25 mL 1% lidocaine in the placebo group which might have produced some therapeutic effect.

All open-label studies showed good efficacy of GON-block for the prophylactic treatment of migraine in adults, adolescents, and children. GON-block reduced the headache severity and frequency in 35% to 68% of patients of CM. However, the headache duration in CM did not decrease with the GON-block.[31] Two open-label studies also showed significant improvement of MIDAS after GON-block.[28],[29] In addition, improvement of anxiety, depression, and sleep quality index was observed after GON-block.[35] The analgesic effects after the GON-block far exceeded the local aesthetic effect of LA. Studies showed that the beneficial effects after a single GON-block persisted for up to 4 weeks[12] and could extend up to 3 months on repeated injection (3 injections) at monthly intervals.[29] Even after a single GON-block, one study reported a significant decrease in NRS at 3 months.[17] More data is needed regarding the predictors of a favorable outcome following GON block in CM as studies reported conflicting results.[14],[24],[32],[70] GON-block has also found to be efficacious for migraine and status migrainosus during pregnancy.[103]

Thus, our review found that the GON-block can be an effective acute and short-term preventive treatment option for migraine patients. Its long-term preventive efficacy however needs to be assessed by further RCTs.

TACs: GON-block has been used successfully for the treatment of different TACs. Literature showed a positive response after GON-block in ECH and CCH,[37],[38],[39],[40],[41],[42],[43],[44] PH,[70] HC,[70],[104] and SUNCT[45],[63],[105],[106] patients.

Two RCTs[37],[38] and 5 open-label studies[39],[41],[42],[43],[44] in CH showed excellent results after GON-block in CH. RCTs observed a significant reduction of attack frequency within 1-2 weeks after the injection and 85% of the patient became attack-free within the first week after injection as compared to none in the placebo group. Similarly, open-label studies also showed a positive response in terms of reduction of attack frequency after GON-block in episodic as well as chronic CH. By and large, the positive response developed within 1-2 weeks after the block and persisted for 3-4 weeks. Mostly the GON-block was used with steroids with or without LA. The only study[40] which did not show significant improvement in CH after the injection used only LA agent (prilocaine) without steroid. Thus, GON-block in CH should include steroids. In fact, two studies used steroids exclusively and found positive results.[38],[44] GOB-block is thus very useful as a transitional preventive in ECH and has also been found to lessen the headache burden in CCH. Also, the systemic side effects of oral steroids which are frequently used during acute cluster periods can be avoided. The evidence of the effectiveness of GON–block in other TACs such as PH,[70] HC,[70] and SUNCT[45] is less robust although a handful of case reports observed a positive and sometimes dramatic outcome in headache relief.

Other primary headaches: GON block was found to be effective in NDPH in 2 case studies.[70],[80] Improvement was also observed in one patient with a hypnic headache.[47] On the contrary, a single open-label pilot study[36] did not observe any improvement at 2 weeks after the GON-block in patients of CTTH. Therefore, more studies are required in these groups of disorders.

Neuralgias: Despite the fact that GON-block primarily developed as a treatment modality for ON, no RCT is available on its use for ON. However, eight studies[69],[71],[72],[73],[74],[76],[77],[78] involving mixed cohorts of headaches patients including ON showed a good efficacy of GON-block in ON.

Secondary headaches: Three most common secondary headache disorders in which GON-block was studied as an acute and preventive therapy are PDPH, MOH, and CGH. Three open-label studies[59],[60],[61] showed significant improvement of headache in PDPH patients immediately after the GON-block and the effect persisted for up to 1-6 weeks. One RCT,[51] 4 open-label studies,[52],[53],[54],[55] and 1 case report[56] observed a good response after GON-block in CGH. GON-block was found to be effective in PTH,[64] SIH,[65] and one patient with orgasmic headache.[46]

RCTs involving a mixed group of headache disorders: Two RCTs[66],[67] that studied the role of GON-block in a mixed population of migraine, THH, CH, NDPH and CGH were difficult to interpret because the efficacy results were not available for the individual headache groups. Nevertheless, both show good efficacy of GON-block in these headache disorders although, in one study,[67] it was inferior to Botulinum toxin in decreasing the pain severity over the long term.

Safety: GON-block was remarkably well tolerated and the TEAE were mild and transient. RCTs in migraine[11],[12],[13],[14],[17] and CH[37],[38] did not observe any serious TEAE. Two absolute contraindications for using GON-block are known allergy to LA and open skull defect craniotomy.[107],[108] Care should be taken for patients who are on anti-platelets and anti-thrombotic agents as local bleeding can occur following GON-block. Post injection, the local site needs to be pressed for 5–10 min.[83] Systemic toxicity has been extremely rare in the recommended doses. Accidental intravascular injection during GON-block can be avoided by withdrawing the plunger before injecting the LA.[81]

Addition of steroids with LA: The addition of steroids to LA was not beneficial in migraine patients as shown by two RCTs (although the sample sizes were small).[9],[10] On the contrary, the combination of LA and the steroid or the steroid alone was found to be very effective in CH.[37],[38],[41],[42],[43],[44] Similarly, steroids were used successfully in addition to LA in patients with CGH,[51],[55] PDPH.[59],[61] Case reports also showed the effectiveness of GON-block with steroids and LA in SUNCT,[63] orgasmic headache,[46] hypnic headache,[45] and SIH.[65] Corticosteroids block the nociceptive C-fibers in substantia gelatinosa reversibly[39] and are also thought to reduce dynamic mechanical allodynia in migraine patients.[20] Effects of LA may also be prolonged by steroids.[109] Various types of steroid preparations have been used that included triamcinolone, MPS, betamethasone, cortivalzole, and dexamethasone. Some specific adverse events such as alopecia, hypo-pigmentation, and cutaneous atrophy can occur with the use of steroids during the GON-block.[110] It should be used with caution in patients with diabetes and glaucoma and repeated blocks with steroids should be avoided as systemic side effects can occur.[111] Long-acting agents like dexamethasone and betamethasone are the preferred choices during pregnancy.[83]

Laterality: One retrospective study suggested that unilateral block may be as good as bilateral blocks in migraine but the sample size was too small.[32] In CH, the GON-block has been given ipsilateral to the side of the headache in most of the studies although in one retrospective study better response after bilateral GON-block[41] was seen. GON-block was used bilaterally in patients with PDPH,[59],[60],[61] hypnic headache,[47] and SIH.[65] It has been shown in experimental animals that the convergent neurons in the TCC have inputs from both the ipsilateral and contralateral cervical afferents.[112],[113] Hence, theoretically, bilateral GON-blocks may provide better results but this awaits confirmation by an RCT.

Localization of injection site: Tender point palpation with the use of standard anatomical landmarks has been used by most of the studies. However, GON has a variable course and few cadaveric studies suggested variable coordinates for the injection site.[114],[115] However, the clinical implications for these variations remain uncertain. Ultrasonography, CT and MRI-guided GON-block aids in better identification of the injection site but probably is difficult to adopt in wider clinical practice. A more proximal injection at the C2 level as compared to the standard site at the superior nuchal line may show more sustained analgesic benefit as shown in a recent RCT.[17] Besides the accuracy of the site of injection, other factors such as posture change (assumption of supine position just after receiving the in sitting position) may enhance the effectiveness of the GON-block injection.[116]

Type of LA: Commonly used amide LA agents such as lidocaine and bupivacaine act by reversibly blocking sodium channels within unmyelinated C-fibers and myelinated nerve fibers that prevent pain signal transmission.[117] Other agents used as LA were prilocaine, ropivacaine, and levobupivacine. Bupivacaine (0.25 or 0.5%) has a longer onset (8–12 min) and duration of action (4 and 8 h) whereas lidocaine (1% -2%) has a rapid onset (4 to 8 min) and shorter duration of action (1 to 2 h) although the former is more cardiotoxic. American Headache Society Special Interest Section for PNBs and other Interventional Procedures (AHS-IPS) has recommended lidocaine concentration of 1%–2% (10–20 mg/mL) and bupivacaine concentration of 0.25%–0.5% (2.5–5 mg/mL) and the volume of injection of 1.5–3 mL per nerve.[83] However, two recent studies have shown an injectate of 5 mL (a cadaveric study)[118] consistently involved most major nerves in the suboccipital area and 10% lidocaine (a retrospective clinical study)[76] may produce a larger area of the block with a greater degree of headache relief. One study also analyzed the TEAE of using lidocaine 1%, 2%, and 5% in 89 consecutive patients of ON and found no significant differences although there was a trend of higher TEAE in the group receiving 5% lidocaine.[119] Few studies used a combination of lidocaine and bupivacaine possibly to augment quicker onset and longer duration of action, the recommended volume ratio (lidocaine/bupivacaine) being 1:1-1:3.[83] The role of additional diluents such as saline to LA remains questionable. Needle gauge sizes of 25, 27, or 30G with a needle length of 0.5 to 1 inch and a 3 to 5 mL syringe is typically used.[81],[83]

Frequency of GON-block: Median duration for a complete and partial response following single GON-block in migraine and CH has been reported as 1–2 weeks[10],[14],[70] and 4–8 weeks[37],[41],[42],[70], respectively. The recommended frequency of GON-block for migraine is therefore once every 2–4 weeks. Some researchers have used an intensive phase of weekly GON-block followed by monthly injections in migraine.[11],[15],[27] In CH, if required, GON-block was repeated in some of the studies.[38],[41],[42],[43] The purpose of the injection is also a deciding factor for repetition. If the GON-block is given for rescue care, repetition is not required when the patient experiences prompt relief after the injection. On the contrary, for transitional care like weaning from pain medication overuse or when preventive medications are yet to establish response, re-treatment may be required with 2-4 weeks interval.


 » Conclusion Top


Our review found good evidence for the beneficial role of GON-block in CH, migraine, PDPH, CGH for acute and short term headache relief. It may also be useful for other uncommon primary and secondary headache disorders based on anecdotal reports but need further evidence. Its role for long-term prevention in migraine, especially CM needs further trials. It is safe, well-tolerated, cheap, and does not have any systemic side effects or drug-to-drug interaction. Hence, it is an attractive option for treating various headache disorders.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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