**4. Classification of the different techniques**

#### **4.1. Noninvasive procedures**

#### *4.1.1. Transcranial electric stimulation (TES)*

This technique involves applying a low amperage continuous electric stimulation directly to the scalp [10]. In most cases, the electric stimulus spreads out of the area covered by the electrodes [10]. AEs have been moderate, such as skin burns due to inadequate electrode skin contact, fatigue or local prickling and burning sensation during the stimulation [8, 10]. Its effectivity and experience are limited [8, 10].

#### *4.1.2. Transcranial magnetic stimulation (TMS)*

A magnetic field is applied to the head, inducing depolarization and electrical activity of the underlying brain cortex [65, 66]. Most have applied it to the left frontal motor area [11, 67, 68], but some have done it to the occipital region, particularly in migraine patients [69]. In chronic headache related to mild posttraumatic head injury (MTHI-H), it has shown ≥50% improvement in pain intensity and frequency in 58.3% of the patients [11]. In migraine, some have reported a reduction of 31.2% in pain frequency and 37.8% in attack duration [70] in two-third of the patients [66]. The acute variant, with or without aura, seems to have a better response than the chronic one [67–72]. There seems to be a cumulative effect, so that the longer this treatment modality is applied, the greater is the attack duration reduction [69]. In migraine patients, a randomised study comparing transcranial magnetic stimulation versus placebo showed a 76.6% versus 27.1% pain improvement [75], but these data were not confirmed by others [68]. Another study in this same disease compared this treatment modality with botulinum toxin injection, finding that although both treatment modalities provide pain relief, the last one is more effective [76]. In atypical facial pain, trigeminal neuropathic pain and cluster headache, it has shown ≥30% pain reduction in 73% of the patients [77]. Interestingly, enough older age and longer treatment duration were associated with a better response, while the type of facial pain showed little influence [77]. It has been applied to pregnant migraine patients with no untoward side effects [69]. Complications are rare and include a case of induced trigeminal autonomic cephalalgia that ceased after stopping the transcranial magnetic stimulation [78]. Some patients have reported transient drowsiness [75]. A continuous application is required for the effects to be persistent [69].

SPGS is both preventive and therapeutic in acute phases [85, 87]. About 30% of the patients can stop the medication [85, 87]. A transoral technique has been described with a remote powering system that avoids extension leads and the need to replace the batteries [86], where patients switch-on the stimulation with a handheld remote controller when the pain attack starts [85]. This markedly reduces the incidence of AEs [86]. Some patients use the stimulation continuously to reduce the attack incidence [85]. Bilateral stimulation is more effective than unilateral [39], but it is not so effective in the chronic variant of this disease [85]. AEs are uncommon and mild, including sensory loss in the maxillary region (81%) [87], that may last over 1 year (2–28%), epistaxis (13%), facial numbness (25%), and local pain (4%) [86]. SPGS

and C<sup>3</sup>

level and tunnelled subcutaneously through a bent Touhy needle inserted

ital nerves). The electrodes (one at each side) can be inserted either through a 2 cm midline

laterally from the mastoid area or alternatively from a lateral approach with a bilateral mastoid area skin incision and the electrodes inserted from a lateral to medial direction with the Touhy needle [14, 60, 88]. As ONS only covers 85% of the head leaving the forehead uncovered, some have combined it with SONS [15, 89, 90]. Percutaneous ONS is recommended to foresee the results of a permanent implantation [91]. In any case, a temporary external stimulation must be performed before definitive implantation [35]. Those with no positive response

ONS has been used in chronic CH [5, 24–26, 28, 29, 32–35, 40], CM [29, 32, 33], TACs [5], hypnic headache (happening regularly sleep) [92], SUNCT/SUNA [93, 94], and occipital neuralgia [32]. In chronic CH, it reduces the attack incidence in over 50% in 70% of patients [5, 24, 25, 28, 33, 40]. In CM, its average success rate is 65.4% in 67.9–80% of the cases [29, 95]. In SUNCT/SUNA, bilateral ONS induced a 69% pain improvement in 77% of the patients [93, 94]. In idiopathic intracranial hypertension, it has been used to treat the associated headache and the residual headache once the intracranial hypertension is resolved, with higher than

AEs plague 33–70% of the cases [24, 25, 29, 33, 96]. Among them are lead erosion [19, 89], local infection [29, 33], electrode emigration [96, 97], lead breakage [28, 30, 33], hardware-related discomfort [98], hardware/stimulation dysfunction [25], and early battery depletion related to high energy consumption [25, 33]. Some technical modifications have been devised to reduce the chance of lead migration [97] that in some series reaches 24% [99]. These include using silicone glue with silicone anchors [100], 2-point anchoring stimulator leads with a tensionrelief loop [26], narrow paddle electrodes [101] and to insert the impulse generator as close as possible to the leads (i.e., supraclavicular area) [96]. Unfortunately, solving the AE entails

Simultaneous ONS and SONS in CH provide more than 50% pain reduction in over 70% of patients [14]. This dual stimulation has also been successful in HM [15] and TACs [19]. Although the results are promising, the number of cases is too small to draw any statistically

75% pain improvement [89], but it requires bilateral stimulation [89].

additional surgical procedures in 26–40.7% of the cases [25, 29].

nerve roots (greater and lesser occip-

Chronic Headache and Neuromodulation http://dx.doi.org/10.5772/intechopen.72150 127

has also been used successfully in CM [44].

are referred to other treatment modalities.

ONS is the stimulation of the distal branches of C<sup>2</sup>

*4.2.2. Occipital nerve stimulation (ONS)*

skin incision at C1

significant conclusions.

### *4.1.3. Transcutaneous supraorbital-supratrochlear stimulation*

This technique involves a special equipment that looks like a pair of glasses, which has to be worn on the forehead. It provides a 50% chronic headache pain reduction, including CM [14, 16, 18]. When used for CM prevention, it reduces the number of attacks but not their intensity [16, 18]. In episodic CM, patients induced a 50% headache frequency reduction in 38.2% of the patients [18]. Although not very effective, the only side effects are local discomfort, redness or temporary skin irritation [16].

#### *4.1.4. Transcutaneous vagus nerve stimulation (VNS)*

The first reports entailed electrodes implanted surgically around the vagal nerve in the neck [79]. However, it never gained acceptance because the procedure was invasive and the results are limited. In 2013, a percutaneous VNS device was introduced, showing promising results in the treatment of chronic CM (CM) [20, 23]. Its best advantage is that it is applied directly to the neck by the patient him/herself [21, 23]. Its main drawback is its low effectiveness (22%) [22, 23, 80]. It is well tolerated with minor side effects like neck twitching, raspy voice or redness at the application site [22, 23, 81].

In CH, it is helpful in the episodic but not in the chronic type [80, 81]. In the episodic type, it induces a positive response in 26.7% of the cases [80]. Some have used it in the acute treatment of the chronic variant of this disease with a higher than 50% pain reduction in 40% of the patients [81]. In CM, it provides a 50% or more pain reduction in 22–56.3% of the patients, which is better in the episodic than in chronic variant [20, 22, 82]. It has been helpful in a single case of hemicrania continua (HC) unresponsive to indomethacin [83].

#### **4.2. Invasive procedures**

#### *4.2.1. Sphenopalatine ganglion stimulation (SPGS)*

The sphenopalatine ganglion has been a target in the treatment of chronic headaches for over a century. Initially, destructive lesions were applied [84], but since 2009, neuromodulation is also available [38]. It is effective in two thirds of episodic CH cases, preventing at least 50% of attacks, showing a decrease in intensity of at least 50% or both [38, 41–43, 73, 74].

SPGS is both preventive and therapeutic in acute phases [85, 87]. About 30% of the patients can stop the medication [85, 87]. A transoral technique has been described with a remote powering system that avoids extension leads and the need to replace the batteries [86], where patients switch-on the stimulation with a handheld remote controller when the pain attack starts [85]. This markedly reduces the incidence of AEs [86]. Some patients use the stimulation continuously to reduce the attack incidence [85]. Bilateral stimulation is more effective than unilateral [39], but it is not so effective in the chronic variant of this disease [85]. AEs are uncommon and mild, including sensory loss in the maxillary region (81%) [87], that may last over 1 year (2–28%), epistaxis (13%), facial numbness (25%), and local pain (4%) [86]. SPGS has also been used successfully in CM [44].

#### *4.2.2. Occipital nerve stimulation (ONS)*

patients, a randomised study comparing transcranial magnetic stimulation versus placebo showed a 76.6% versus 27.1% pain improvement [75], but these data were not confirmed by others [68]. Another study in this same disease compared this treatment modality with botulinum toxin injection, finding that although both treatment modalities provide pain relief, the last one is more effective [76]. In atypical facial pain, trigeminal neuropathic pain and cluster headache, it has shown ≥30% pain reduction in 73% of the patients [77]. Interestingly, enough older age and longer treatment duration were associated with a better response, while the type of facial pain showed little influence [77]. It has been applied to pregnant migraine patients with no untoward side effects [69]. Complications are rare and include a case of induced trigeminal autonomic cephalalgia that ceased after stopping the transcranial magnetic stimulation [78]. Some patients have reported transient drowsiness [75]. A continuous

This technique involves a special equipment that looks like a pair of glasses, which has to be worn on the forehead. It provides a 50% chronic headache pain reduction, including CM [14, 16, 18]. When used for CM prevention, it reduces the number of attacks but not their intensity [16, 18]. In episodic CM, patients induced a 50% headache frequency reduction in 38.2% of the patients [18]. Although not very effective, the only side effects are local discomfort, redness or

The first reports entailed electrodes implanted surgically around the vagal nerve in the neck [79]. However, it never gained acceptance because the procedure was invasive and the results are limited. In 2013, a percutaneous VNS device was introduced, showing promising results in the treatment of chronic CM (CM) [20, 23]. Its best advantage is that it is applied directly to the neck by the patient him/herself [21, 23]. Its main drawback is its low effectiveness (22%) [22, 23, 80]. It is well tolerated with minor side effects like neck twitching, raspy voice or red-

In CH, it is helpful in the episodic but not in the chronic type [80, 81]. In the episodic type, it induces a positive response in 26.7% of the cases [80]. Some have used it in the acute treatment of the chronic variant of this disease with a higher than 50% pain reduction in 40% of the patients [81]. In CM, it provides a 50% or more pain reduction in 22–56.3% of the patients, which is better in the episodic than in chronic variant [20, 22, 82]. It has been helpful in a single

The sphenopalatine ganglion has been a target in the treatment of chronic headaches for over a century. Initially, destructive lesions were applied [84], but since 2009, neuromodulation is also available [38]. It is effective in two thirds of episodic CH cases, preventing at least 50% of

attacks, showing a decrease in intensity of at least 50% or both [38, 41–43, 73, 74].

case of hemicrania continua (HC) unresponsive to indomethacin [83].

application is required for the effects to be persistent [69].

*4.1.3. Transcutaneous supraorbital-supratrochlear stimulation*

*4.1.4. Transcutaneous vagus nerve stimulation (VNS)*

temporary skin irritation [16].

126 Transcranial Magnetic Stimulation in Neuropsychiatry

ness at the application site [22, 23, 81].

*4.2.1. Sphenopalatine ganglion stimulation (SPGS)*

**4.2. Invasive procedures**

ONS is the stimulation of the distal branches of C<sup>2</sup> and C<sup>3</sup> nerve roots (greater and lesser occipital nerves). The electrodes (one at each side) can be inserted either through a 2 cm midline skin incision at C1 level and tunnelled subcutaneously through a bent Touhy needle inserted laterally from the mastoid area or alternatively from a lateral approach with a bilateral mastoid area skin incision and the electrodes inserted from a lateral to medial direction with the Touhy needle [14, 60, 88]. As ONS only covers 85% of the head leaving the forehead uncovered, some have combined it with SONS [15, 89, 90]. Percutaneous ONS is recommended to foresee the results of a permanent implantation [91]. In any case, a temporary external stimulation must be performed before definitive implantation [35]. Those with no positive response are referred to other treatment modalities.

ONS has been used in chronic CH [5, 24–26, 28, 29, 32–35, 40], CM [29, 32, 33], TACs [5], hypnic headache (happening regularly sleep) [92], SUNCT/SUNA [93, 94], and occipital neuralgia [32]. In chronic CH, it reduces the attack incidence in over 50% in 70% of patients [5, 24, 25, 28, 33, 40]. In CM, its average success rate is 65.4% in 67.9–80% of the cases [29, 95]. In SUNCT/SUNA, bilateral ONS induced a 69% pain improvement in 77% of the patients [93, 94]. In idiopathic intracranial hypertension, it has been used to treat the associated headache and the residual headache once the intracranial hypertension is resolved, with higher than 75% pain improvement [89], but it requires bilateral stimulation [89].

AEs plague 33–70% of the cases [24, 25, 29, 33, 96]. Among them are lead erosion [19, 89], local infection [29, 33], electrode emigration [96, 97], lead breakage [28, 30, 33], hardware-related discomfort [98], hardware/stimulation dysfunction [25], and early battery depletion related to high energy consumption [25, 33]. Some technical modifications have been devised to reduce the chance of lead migration [97] that in some series reaches 24% [99]. These include using silicone glue with silicone anchors [100], 2-point anchoring stimulator leads with a tensionrelief loop [26], narrow paddle electrodes [101] and to insert the impulse generator as close as possible to the leads (i.e., supraclavicular area) [96]. Unfortunately, solving the AE entails additional surgical procedures in 26–40.7% of the cases [25, 29].

Simultaneous ONS and SONS in CH provide more than 50% pain reduction in over 70% of patients [14]. This dual stimulation has also been successful in HM [15] and TACs [19]. Although the results are promising, the number of cases is too small to draw any statistically significant conclusions.

#### *4.2.3. Great auricular nerve stimulation (GANS)*

Pain relief was reported using this technique in a single case of persistent MTHI-Ha 90% [37]. Further studies are needed.

**5. Indications and results for specific chronic headache disorders**

CH consists of bouts of unilateral periorbital pain lasting between 15 minutes and 3 hours that follow an annual pattern [105]. It is considered as the most painful headache type, with 0.12% prevalence. About 10% of the cases cannot be controlled with medical treatment [34]. CH has two variants: chronic and episodic [106]. In the episodic, headache periods alternate with others of remission, and the attacks last between 7 days and 1 year with a pain free period lasting at least 1 month [105]. The chronic variant represents 10–15% of the cases [34, 86] and has free pain periods shorter than 1 month or attacks that are present nonstop

Chronic Headache and Neuromodulation http://dx.doi.org/10.5772/intechopen.72150 129

Percutaneous VNS has been used in the acute treatment of the chronic variant of CH with a higher than 50% pain reduction in 40% of the patients [33, 42, 81, 107]. Although not univer-

Both ONS [25, 26, 34] and SPGS [40–43, 73] are the first options among the invasive techniques [5, 86]. About 70% of patients respond to these treatments with 48% of excellent responders [25, 34]. ONS together with SONS has been applied with >50% pain reduction in 71% of the patients [90]. Cervical SCS has also been used with some success [102]. hDBS should be left as the very last resource as its complications are more severe and potentially

It is a continuous and unilateral headache (it only affects one side of the head), associated autonomic symptoms and episodes of increased headache intensity [105]. Indomethacin is the drug of choice, but some patients do not tolerate it due to side effects like hypertension, gastrointestinal problems (particularly when combined with aspirin), vascular events, or bronchial spasms [83]. In a single case, it was found to respond to noninvasive percutaneous VNS [83]. Others tried repetitive sphenopalatine ganglion block [108]. The data are not statistically

CM is described as having migraine headaches 15 or more days in every month [99]. Worldwide, it is the seventh cause of disability [109]. It affects 2–5% of the adult population [3, 105, 110].

The transcranial stimulation has contradictory results, so no recommendations can be offered [9]. The cervical percutaneous VNS shows promising but moderate results, better in the episodic than in chronic variant [20, 111]. Transcutaneous SONS reduces the number of attacks but not its intensity [18, 111]. Much more efficient is the ONS via implanted electrodes [5, 24, 29, 46], with a success rate of 65.4% in 67.9–80% of the cases [29, 95].

sally effective, it is minimally invasive and with very minor and reversible AEs.

**5.1. Cluster headache (CH)**

through at least 1 year [105].

life threatening [5, 52].

**5.2. Hemicrania continua (HC)**

**5.3. Chronic migraine (CM)**

significant, and no definite conclusions can be drawn.

### *4.2.4. Supraorbital nerve stimulation (SONS)*

The first case was reported in 2009 in the treatment of CH [36]. In this disorder, SONS produced more than 50% pain reduction in 71% of the patients [19, 36, 90]. In a series of five patients with TACs, it improved the pain in all of them, but the series is too short to draw any conclusions [19]. It can be used alone or associated with ONS [14, 15, 19, 90].

#### *4.2.5. Cervical spinal cord stimulation (SCS)*

The electrode is introduced in the epidural space at the upper thoracic level and advanced to the cervical spinal cord until its distal tip is at the C2 level. One or two electrodes are inserted. The leads are connected to a subcutaneous impulse generator inserted at the infraclavicular area [46].

SCS has been used in CM [46, 47], SUNA [54], CH [45, 64], and MTBI-HA [48], reducing the headache frequency and/or intensity by ≥50% in 71% of the patients [45–47]. In CM, it improves the headache by >30% in 50% of the cases [46, 47, 102]. The AEs are frequent (71%) and usually require system explant and replacement in a second surgery [102]. Among these AEs are infections (13%) and lead rupture or migration (17%) [45–47, 89].

#### *4.2.6. Hypothalamic deep brain stimulation (hDBS)*

hDBS was introduced in 2000 to treat drug-resistant CH [61]. It is useful in many types of chronic headache disorders like HC, CH, SUNCT/SUNA, and in TACs [4, 50]. In chronic CH, it results in reduction of ≥50% of the attacks in 60% of the patients [5, 40, 50, 52]. The response rate in HC and SUNA is 82% [49]. In TACSs, the improvement rate is >50% in 69.9% of patients [50].

AEs include incision site pain, subcutaneous dislodgement of the impulse generator, transient gaze disturbance (oscillopsia, diplopia), autonomic disturbances, myosis, dizziness, wound infection, cervical dystonia, intracranial haemorrhage, and lead disconnection or rupture [40, 49, 52]. Many of these complications require system explant [49]. hDBS is reserved for those very few cases, in which everything else has failed as death has been reported [50].

The target was initially in the posterior hypothalamus [103, 104], but other areas have also been used like the mesencephalic grey substance, the red nucleus, the fasciculus retroflexus, the dorsal longitudinal fasciculus, the ansa lenticularis, the medial longitudinal fasciculus or the medial thalamus superficialis [104]. In the latest years, the ventral tegmental area is used to decrease the chance of haemorrhages [49, 52].
