The role of interventional pain procedures in Migraine and Cluster Headache

1.
Trattamenti interventistici
nelle Cefalee
Dr. Gaetano Terranova
U.O. Medicina del Dolore
ASST Lodi

2. https://www.ichd-3.org

3. Migraine

4. Lifetime prevalence : 14700/100,000
1-year prevalence: 11300/100,000
Female to male ratio: 3
Prevalence: 14,7% Mundial population
5% of migraine! Transformed migraine, chronic daily
headaches
3-13% of migraine! Chronic migraine
1-2% of migraine! Refractary to medical therapy
(Preventive medication
Migraine! second most frequently identified cause of
short-term absence (47%)
Migraine ! cost the NHS in the UK £150 million per year
Epidemiology of Migraine

5. 79% of patients reported
restrictions in their daily living
because of CH.
13% reported inhibition also outside
of cluster periods.
Jensen RM et all., Burden of Cluster Headache
June 1,2007
Epidemiology of Cluster Headache
Lifetime prevalence : 124/100,000
1-year prevalence: 53/100,000
Male to female ratio: 4.3
Episodic CH vs chronic CH: 6.0
4-13% Episodic -> Became Chronic
12% Episodic-> Prolonged
spontaneus
remission
55% of Chronic -> Persist
10-20% of CH-> Drug resistant
Episodic CH-> 6000€/year
Chronic CH-> 20000€/year
Fischera, 2008 Headache

6. Interventional
Pain Procedures
in Headache
(Rescue
Therapies):
• Cluster
Headache
• Chronic
Migraine
• Medication
overuse

7. Pathophysiology of migraine

8. Visual cotex
Trigeminocervical complex
ON, OFF,
Neutral cell
Migraine: a neurobiological disorder
Cortical Spreading
Depression

9. The migraine network
Target of interventional procedures in
migraine:
- Trigeminocervical complex! more
frequently used: occipital nerve

10. Indications occipital nerve block:
1. Migraine
Migraine with aura
Migraine without aura
Status migrainosus
Chronic migraine
2. Tension-type headache
3. Cluster headache
4. Chronic daily headache
5. Hemicrania continua
6. New daily persistent headache
7. Cervicogenic headache
8. Posttraumatic headache
9. Post-dural puncture headache
10. Occipital neuralgia
11. Trigeminal neuralgia
12. Tapering medication overuse
M.A. Mays and S.J. Tepper

11. Peripheral Nerve Blocks
Evidence Base
Despite the common use of peripheral nerve blocks in the care of
patients with headache, there has been no standard approach for
the performance of this procedure. A survey D.F. Garcia-Roves et
al.465 conducted by the American Headache Society SpecialI
interest Section for Peripheral Nerve Blocks and other
Interventional Procedures (AHS-IPS) showed that 69% of
responding providers used the technique, but the pattern of use,
dosages, volumes, and injection schedules varied greatly .
Considering this, an endeavor was initiated by the AHS-IPS trying to
establish a standardized peripheral nerve block methodology.
Blumenfeld A, Ashkenazi A, Napchan U, et al. Expert consensus recommendations for the performance of peripheral nerve blocks for headaches: a narrative review.
Headache. 2013;53:437–46.

12. Robbins et al., Headache 2016
Efficacy, Adverse Events, Level of Evidence and Recommentations for the Prophylactic Therapy of
Cluster Headache

13. MEDICATION OVERUSE
HEADACHE (MOH)
Ensure patient is on
optimal doses of
prophylactic meds
Wean off the responsible
abortive meds
Behaviour therapy and
psychological support
Consider other interventions to
help during the weaning process
TREATMENT MEDICATION OVERUSE:
Evidence shows that the majority of patients with this disorder improve after:
• Discontinuation of the overused medication, as does their
responsiveness to preventative treatment.
• Simple advice on the causes and consequences of Medication-
overuse headache is an essential part of its management. An explanatory
brochure is often all that is necessary to prevent or discontinue medication
overuse.
• Prevention is especially important in patients prone to frequent headache.
• GON Block may be consider to help tapering medication (Case series, RR)
Occipital nerve
block

14. Ultrasound guided GON Block
1. Ultrasound guided occipital nerve block: The procedure can be
performed either distally at the nuchal line or more proximally
between C1 and C2
• Blumenfeld A, Ashkenazi A, Napchan U, et al. Expert consensus recommendations for the performance of peripheral
nerve blocks for headaches–a narrative review. Headache. 2013;53:437-446.
• Ashkenazi A, Blumenfeld A, Napchan U, et al. Interventional procedures special interest section of the American.
Peripheral nerve blocks and trigger point injections in headache management– a systematic review and suggestions
for future research.Headache. 2010;50:943-952.

15. THE ROLE OF ULTRASOUND IN DIAGNOSIS
THE ETIOLOGY OF OCCIPITAL NEURALGIA
1. Diagnosis of occipital nerve entrapment: by demonstrating enlarged,
abnormal, swollen nerve:
• The normative sonographic data indicate that the GON cross-sectional area is 2.060.1 mm2 at C1-2
level. The mean GON cross-sectional area in symptomatic patients following entrapment was
4.162.6 mm2
• Mosser SW, Guyuron B, Janis JE, Rohrich RJ. The anatomy of the greater occipital nerve: Implications for the etiology of migraine headaches. Plast Reconstr Surg. 2004;113:693-697
• Narouze S, Souzdalnitski D. Occipital nerve entrapment the semispinalis capitis muscle diagnosed with ultrasound. Cephalalgia.2013;33:1358-1359.
• Cho JC, Haun DW, Kettner NW. Sonographic evaluation of the greater occipital nerve in unilateral occipital neuralgia.J Ultrasound Med. 2012;31:37-42.
10. Greher M, Moriggl B, Curatolo M,

16. 2. Diagnosis of the cause of entrapment:
• entrapment within the suboccipital muscles
• impingement by arterial vessels impingement
by venous aneurysms/malformations
• muscle space occupying lesion

17. Pulsed radiofrequency of GON

19. Ultrasound guided occipital peripheral nerve pulsed radiofrequency
in occipital neuralgia (2C - to be consider)
In February 2016, there are 2 prospective studies and one retrospective multicenter study with
promising results.
• Vanelderen P, Rouwette T, De Vooght P, Puylaert M, Heylen R, Vissers K, Van Zundert J. Pulsed radiofrequency for the
treatment of occipital neuralgia: A prospective study with 6 months of followup. RegAnesth Pain Med. 2010;35:148-151.
• Choi, HJ, Oh IH, Choi SK, Lim YJ. Clinical outcomes of pulsed radiofrequency neuromodulation for the treatment of occipital
neuralgia. J Korean Neurosurg Soc. 2012;51:281-285.
• Huang JHY, Galvagno SM Jr, Hameed M, et al. Occipital nerve pulsed radiofrequency treatment: A multi-center study evaluating
predictors of outcome. Pain Med. 2012; 13:489-497.

20. OCCIPITAL NERVE STIMULATION
Indications
Occipital nerve stimulation (ONS) offers the potential for a
minimally invasive, low-risk, and reversible approach to
managing intractable headache disorders contrary to
neuroablative techniques.
ONS had been used successfully in the treatment of:
• Occipital neuralgia 1 – 4 (Level III of Evidence)
• Chronic migraine and headache5 (Level II of Evidence)
• Transformed migraine 4
• Cluster headache 5 – 9 (Level II of Evidence)
• Hemicrania continua 6 , 10 (Level II of Evidence)
References
1. Weiner RL, Reed KL. Peripheral neurostimulation for control of intractable occipital neuralgia. Neuromodulation. 1999;2:217–21.
2. Kapural L, Mekhail N, Hayek SM, Stanton-Hicks M, Malak O. Occipital nerve electrical stimulation via the midline approach and subcutaneous surgical leads for treatment of
severe occipital neuralgia: a pilot study. Anesth Analg. 2005;101:171–4.
3. Johnstone CHS, Sundaraj R. Occipital nerve stimulation for the treatment of occipital neuralgia-eight case studies. Neuromodulation. 2006;9:41–7.
4. Oh MY, Ortega J, Bellotte JB, Whiting DM, Alo K. Peripheral nerve stimulation for the treatment of occipital neuralgia and transformed migraine using a C1-2-3
subcutaneous paddle style electrode: a technical report. Neuromodulation. 2004;7:103–12.
5. Schwedt TJ, Dodick DW, Hentz J, Trentman TL, Zimmerman RS.Occipital nerve stimulation for chronic headache-long-term safety and effi cacy. Cephalalgia. 2007;27:153–7.
6. Schwedt TJ, Dodick DW, Trentman TL, Zimmerman RS. Occipital nerve stimulation for chronic cluster headache and hemicrania continua: pain relief and persistence of
autonomic features. Cephalalgia. 2006;26:1025–7.
7. Burns B, Watkins L, Goadsby PJ. Treatment of medically intractable cluster headache by occipital nerve stimulation: long-term follow- up of eight patients. Lancet.
007;369:1099–106.
8. Burns B, Watkins L, Goadsby PJ. Treatment of intractable chronic cluster headache by occipital nerve stimulation in 14 patients. Neurology. 2009;72:341–5.
9. Magis D, Allena M, Bolla M, De Pasqua V, Remacle JM, Schoenen J. Occipital nerve stimulation for drug-resistant chronic cluster headache: a prospective pilot study. Lancet
Neurol. 2007;6:314–21.
10. Burns B, Watkins L, Goadsby PJ. Treatment of hemicrania continua by occipital nerve stimulation with a bion device: long-term follow-up of a crossover study. Lancet
Neurol. 2008;7:1001–12.

21. Limited evidence suggested that response to occipital
nerve block may not be a useful predictor for
response to ONS treatment. While a subgroup analysis
from the PRISM trial and a small case series suggested
that ONS is more effective in patients without
medication overuse,the observed effectiveness was
similar between the ONSTIM trial (which excluded
patients with medication overuse) and the other trials
which allowed patients with medication overuse,
including the crossover trial by Serra and Marchioretto in
which 85% of the patients with chronic migraine also met
the criteria for medication overuse .

22. OCCIPITAL NERVE STIMULATION
Technical Problems and Complications:
• lead migration. (The major technical problem )The incidence of lead migration was 24 % after 3
months . In another review it was found to be 60 % 1 year postimplant and 100 % 3 year post-
implant .This led some practitioners to consider the use of self-anchoring leads in ONS with
encouraging preliminary results .None of the 12 patients required a surgical revision for lead
migration for a mean follow-up period of 13 months .
• occipital muscle spasms due to occipital muscle stimulation secondary to improper
leadplacement as described above
• lead fracture or disconnect, lead tip erosion, infection, unpleasant stimulation, and localized
pain at implant sites .

23. 10KHz SPINAL CORD STIMULATION IN CHRONIC REFRACTORY HEADACHE
17 pts

24. Clinical algorithm
Philosophy for this algorithm:
• Treatment >>> Simple to complex
• Degree of invasiveness>>> Minimal to major
• Overall cost >>> Least to most

25. CHRONIC MIGRAINE
Review possible causes
of chronicity; reverse
them
No medications overuse
headache (MOH)
Medications overuse
headache (MOH)
Botox injection
No response
IV infusions
No response
Chronic migraine
especially with
occipital pain
Occipital nerve blockPRF Occipital Nerve
Occipital nerve
stimulation
Chronic migraine
especially with
autonomic features
Sphenopalatine
ganglion block
Sphenopalatine
stimulation
OnaBoNT-A should be offered as a
treatment option to patients with CM
to increase the number of headache-
free days.
OnaBoNT-A should be considered to
reduce headache impact on health-
related quality of life.
PRF SPG
Ensure patient is on
optimal doses of
prophylactic meds
Wean off the responsible
abortive meds
Behaviour therapy and
psychological support
Consider other interventions to
help during the weaning process
Occipital nerve
block

26. OnabotulinumtoxinA is the only treatment approved by
the US Food and Drug Administration for the prevention
of headaches in patients with chronic migraine (CM).The
mechanism of action of onabotulinumtoxinA in treating
pain is most likely related to the inhibition of nociceptive
mediator release from afferent neurons, thereby
attenuating peripheral pain signaling to the brain. The
efficacy of onabotulinumtoxinA as a prophylactic
treatment for CM may be attributed to the notion that
extracranial administration decreases the release of
nociceptive mediators and decreases the sensitivity of
meningeal receptors through downregulation of their
activity.
The PREEMPT studies used a fixed-site, fixed-dose
injection paradigm where intramuscular injections of 155
Units of onabotulinumtoxinA were administered across 7
head and neck muscles and allowed physician discretion
to inject an additional 40 Units of onabotulinumtoxinA
across 3 muscle groups (the follow-the-pain approach).
OnabotulinumA for Chronic Migraine: The PREEMPT Study
Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, Diener HC, Brin MF, PREEMPT 1 Chronic Migraine Study
Group OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the
PREEMPT 1 trial. Cephalalgia. 2010;30:793–803. doi: 10.1177/0333102410364676

27. Cluster Headache
Attacks of severe, strictly unilateral pain which is orbital, supraorbital,
temporal or in any combination of these sites, lasting 15–180 minutes and
occurring from once every other day to eight times a day. The pain is
associated with ipsilateral conjunctival injection, lacrimation, nasal
congestion, rhinorrhoea, forehead and facial sweating, miosis, ptosis and/or
eyelid oedema, and/or with restlessness or agitation.
Episodic
At least 2 cluster
remission >1 month
Chronic
Clusters occurring without a remission perio
or with remissions lasting < 1 month,
for at least 1 year

28. Schematic pathway representation summarizing the trigeminal-parasympathetic reflex
May, A. et al. (2018) Cluster headache
Nat. Rev. Dis. Primers doi:10.1038/nrdp.2018.6

29. The autonomic nervous system

30. Sphenopalatine ganglion anatomy
The SPG is located in the pterygopalatine fossa (PPF). The SPG has
rich parasympathetic (preganglionic axons and postganglionic cell
bodies and axons) and sympathetic (postganglionic axons)
components. The parasympathetic preganglionic cell bodies
projecting to the SPG originate in the superior salivatory nucleus
(SSN) of the facial nerve in the pons.
SPG block indication:
• Medically resistant cluster headaches
• Migraine
• Trigeminal autonomic cephalalgias
• Intractable orofacial pain syndromes

31. Spheno-palatine ganglion Block
Kwo Wei David Ho, Rene Przkora and Sanjeev Kumar. Sphenopalatine ganglion: block,
radiofrequency ablation and neurostimulation - a systematic review. The Journal of Headache and Pain (2
Case series and observational studies have
demonstrated its utility for treatment of
painful syndromes, with the based designed
study reaching 1C level of utility.

32. Intra-nasal Approch

33. Spheno-palatine ganglion radiofrequency
1. Sanders M, Zuurmond W. Efficacy of sphenopalatine ganglion blockade in 66 patients
suffering from cluster headache: a 12- to 70-month follow-up evaluation. J
Neurosurg. 1997;87:876–80.
2. Kwo Wei David Ho, Rene Przkora and Sanjeev Kumar. Sphenopalatine ganglion: block,
radiofrequency ablation and neurostimulation - a systematic review. The Journal of
Headach e and Pain (2017) 18:118
Sanders and Zuurmond did a case series on
SPG RFTC, which included 66 patients with a
diagnosis of episodic and chronic cluster
headaches.
–– 34 of 56 patients with episodic and 3 of 10
with chronic headaches reported complete
resolution of headaches during a mean
follow-up of 29 months.
R e c c o m a n d a t i o n 1 C ( s t r o n g
recommendation, low- or very-low-quality
evidence)
• SPG radiofrequency ablation (RFA) is
a valuable option to those patients
suffering from intractable chronic
cluster headaches, who responded
favorably – but only temporary to SPG
blocks.

35. Infra zigomatic Approch

36. Complications of SPG Block and RF Neurolysis
• Epistaxis is more common after nasal topical application of local
anesthetic; however, it can occur with the infrazygomatic approach if
the needle is advanced too far medially through the lateral nasal
wall .
• Intravascular injection and hematoma formation can occur after
maxillary artery or branches injury, which are located within the
pterygopalatine fossa However; cheek hematoma is more common but
much more benign deep hematomas.
• Infection is always a possibility, although very rare, if the oral or
nasal mucosa was accidentally penetrated
• Reflex bradycardia was reported during radiofrequency lesioning,
which could be explained by the rich parasympathetic connections to
the SPG .
• Radiofrequency lesioning of the SPG can result in permanent or,
more commonly, temporary hypoesthesia or dysesthesia in the
palate, maxilla, or posterior pharynx. Pulsed radiofrequency would
seem to be safer; however, there is limited data for its effi cacy .
• Dryness of the eye as a result of interruption of the
parasympathetic supply is also common; however, it is usually only
temporary.
• Temporary diplopia, which is more common after local anesthetic
injections rather than RFA, can be explained by the spread of the
injectate from the pterygopalatine fossa to the inferior orbital fi ssure
containing the abducent nerve . This is the reason why we limit the
injectatevolume to only 1–2 ml).

37. Robbins et al., Headache 2016
SPG Stimulation
Ambrosini A. et al., Cephalalgia 2015;
Schoenen et al., Cephalalgia 2012
Headache Center - MRI Research Center SUN-FISM - Second University of
Naples

38. Hypothalamus and CH
1. Radiological findings
• PET
• MR
2. Endocrinological findings
• Reduced melatonin
• Phase advance in 24 h melatonin
• Changes in production of cortisol, prolactin, sex hormones
• Hypocretin polymorphism(?)
3. Chronobiological features
• Diurnal rhythmicity
• Annual rhythmicity
4. Other findings
• Deep brain stimulation of the posterior hypothalamus is
efficacious

39. Deep brain stimulation
Summary:
• Long-term effect only (weeks/months)
• No acute abortive effect
• Not effectful in all patients, but more than 50%.
• Frequency and intensity of headache ↓. Some totally painfree.
• Pain returns to baseline when turning stimulator off.
• Significant side effects in some patients.
Proposed way of mechanism
1. A blockade of a local cluster generator located in suprachiasmatic nucleus, mesencephalon or TNC
2. A non specific anti-nociceptive effect by activation of the PAG and/or RVM pain modulatory system.
3. A long term modulation of neuronal pain-processing pathways
AE’s
Perioperatively: Diplopia, vertigo, mood changes, panic attacks, syncope, hemiparesia, loss of consciousness,
transient ischaemia, intracerebral hemorrhage and death Polydipsia, infection, electrode migration, electrode
dysfunction, battery problems.(Not from CH: apathy, hallucinations, compulsive gambling, hypersexuality,
cognitive dysfunction, and depression, personality changes.

40. CLUSTER
HEADACHE
Review possible causes
of chronicity; reverse
them
(for prophylactic
treatment)
Occipital nerve block
Occipital nerve
stimulation
especially with
autonomic features
(for acute and
prophylactic treatment)
Sphenopalatine
ganglion block
Sphenopalatine
stimulation
PRF SPG

41. Future and emerging treatments
• Further researches are needed for RF
• Neurostimulation for episodic patients
• Wireless neurostimulator
• CGRP antagonists
• Transcranial magnetic stimulation
• t-SNS

42. -Conventional pharmacological therapies for
migraine and cluster are often inadequate and
substantial proportions of migraine and cluster
patients are considered “refractory” to current
therapies.
-Non-invasive neurostimulation could serve an
important adjunctive role in the abortive and
preventive treatment of migraine and cluster
headache.
-Interventional pain procedures(nerves blocks,
radiofrequency and neurostimulation) might
play a role in the treatment of patients with severe
migraine and cluster who are otherwise treatment
refractory.
- Multi-moldal approch might provide a better
management of migraine and cluster.