Pathophysiology of MH

Though migraine pathophysiology has not been completely elucidated, there are several plausible and experimentally substantiated theories. Importantly, these explanations incorporate both central and peripheral nervous-system activity, and these factors interact and lead to MH. There are four mechanisms in the pathogenesis of MH.¹⁵ First, patients with MH have some experimental evidence of interictal cortical derangements, specifically hyperexcitability of cortical neurons. Second, periaqueductal gray matter (PAG), which is an antinociceptive modulator, becomes progressively dysfunctional in MH. Burstein¹⁴ provided evidence that the sensitization of nociceptors causes an increase in neuronal discharges, which causes an increase in sensitivity to all stimuli. In other words, the central nervous system is ramped up, compared to normal, in response to both normal and painful stimuli. Third, auras are caused by cortical spreading depression, and the cortical spreading depression itself might cause irritation of the trigeminal nerve nucleus caudus.¹⁵ Finally, trigeminal nerve irritation causes release of substance P, calcitonin gene-related peptide, and neurokinin A in the cell bodies of the trigeminal nerve.^15–17 The substances then travel along the nerve and produce a localized meningitis, and dilation of large vessels and dura mater innervated by the trigeminal nerve.^1,2,15,18,19 Although this dilation is thought to cause MH, in our view it is the consequence of inflammation.

What causes the initial trigeminal nerve irritation is not exactly known. The anatomic relationship between trigeminal nerve branches and head and neck musculature provides the basis of the trigger site hypothesis of trigeminal nerve irritation in our opinion. Triggers sites are where nerves are irritated either by traversing the muscle or due to contact with it. This concept is borne out by anatomic studies. The trunk of the supratrochlear nerve, and branches of the supraorbital, which are both branches of the ophthalmic division of the trigeminal nerve, pierce the corrugator and depressor supercilii. The fact that many patients with MH have evidence of corrugator hypertrophy provides support for this hypothesis, which is further reinforced by the beneficial effects attained from injection with botulinum toxin A. Branches of the ZMTBTN pierce the temporalis muscle. The greater occipital nerve pierces the semispinalis capitus muscle.^20,21 In some ways, this is analogous to piriformis syndrome, in which contraction of the piriformis muscle results in sciatic nerve irritation.^22,23

Like MH, the pathophysiology of cluster headaches is not well understood. What is known is that pain in cluster headaches is mediated by the first division of the trigeminal nerve, while autonomic activation is mediated by cranial parasympathetic outflow from the facial nerve. There is no brainstem activation in cluster headaches, which distinguishes it pathophysiologically from MH.²⁴

Rationale for surgical treatment

In 1931, Walter Dandy removed the inferior cervical and first thoracic sympathetic ganglions in two patients, hypothesizing that migraine pain had a clinical profile consistent with nerve involvement.²⁵ In 1946, Gardner reported on the resection of the greater superficial petrosal nerve in 26 patients. Though he reported some success in migraine patients, he noted complications including nasal dryness, decreased tear production, and corneal ulcerations.²⁶ Slightly more than two decades later, Murillo described temporal neurovascular bundle resection in 34 patients for treatment of migraine headaches.²⁷ Shortly after, Murphy reported greater occipital neurectomy for occipital migraine.²⁸ Murillo and Murphy both had shortcomings in the length of follow-up of their studies, and there was a sequela of numbness resulting from these procedures. These radical surgeries with morbid sequelae led to unacceptable surgical outcomes, but the idea that surgery has potential in the treatment of headaches has persisted.

Recent observations have supported new, safer, surgical protocols. In the senior author’s practice the fortuitous discovery that several patients who had undergone forehead rejuvenation procedures had resolution of their MH led to the development of surgical protocols to treat refractory headaches.

The understanding that the glabellar muscle group (GMG, including the corrugator, depressor supercilii, and procerus) itself may contribute to the pathophysiology, means that resection of these muscles makes intuitive sense. Not only do these patients benefit functionally from the surgery, they also observe some aesthetic improvement. Furthermore, the involvement of the ZMTBTN, which is sometimes resected in facial rejuvenation procedures,² makes transection of that nerve justifiable for the treatment of headaches, since temporalis muscle resection may result in a depression and may also be of some, although minor, functional consequence.

Trigger sites

Currently, there are four common trigger sites: frontal triggers, where glabellar muscles irritate the supratrochlear and supraorbital nerves and cause frontal headaches; temporal triggers, where contraction of the temporalis muscle causes inflammation of the ZTBTN and causes temporal headaches; occipital triggers, where the semispinatus capitus stimulates the occipital nerve and causes occipital headaches; and septonasal triggers, where intranasal structures compress the trigeminal end branches and cause paranasal and retrobulbar headaches.20,21,29 There are several less common trigger sites, most of which are at intersections of nerves and arteries, such as the superficial temporal artery and the auriculotemporal nerve, or the greater occipital nerve and occipital arteries. The constellation of the symptoms that aid in detection of the trigger sites have been outlined in Table 22.2.

Table 22.2 The constellation of symptoms that aid in the diagnosis of migraine headache trigger sites

The role of botulinum toxin A

Botulinum toxin A (Botox, Allergan, Irvine, California) blocks the release of acetylcholine at the neuromuscular junction; a deadly neurotoxin produced by Clostridium botulinum, its clinical utility for in MH has only been recently discovered.^30,31. Clostridium botulinum actually produces seven subtypes of the neurotoxin-labeled A, B, C, D, E, F, and G, each of which has its own cellular substrate and target cleavage site.

It was first introduced over three decades ago as a treatment for strabismus,^32–35 and since has been used in many neuromuscular conditions, including oromandibular dystonia, laryngeal dystonia, cervical dystonia, writer’s cramp, and hemifacial spasm.³⁵

At the time of this writing, the use of botulinum toxin A for clinical treatment of migraines is investigational and still controversial.^36–38 We use botulinum toxin A to confirm suspected trigger sites.

The trigger points are injected systematically, starting with the most common and severe trigger site based on the patient’s reported symptoms and physical examination. This is most often the corrugator supercilii muscle. First, 12.5 U of botulinum toxin A are injected with a long 30-gauge needle into the glabellar muscle sites. Trigger sites are injected 1 month apart, up to a maximum of 3. Patients then keep a headache diary, and refrain from taking prophylactic migraine medication. Those patients with trigger sites that respond, either completely or partially (defined as a 50% reduction of headache intensity or frequency from baseline for 4 weeks), to botulinum toxin A are considered for surgical intervention² (Fig. 22.3). Nerve blocks could be used similarly.

Fig. 22.3 Algorithm for diagnosis of MH using botulinum toxin. Trigger sites are injected with 12.5 U of botulinum toxin with a 1 inch long 30-gauge needle. Improvement is operationally defined as a 50% reduction of headache intensity or frequency from the baseline for 4 weeks. (Redrawn from Guyuron B, Kriegler JS, Davis J, et al. Comprehensive Surgical Treatment of Migraine Headaches. Plast Reconstr Surg 115(1):1-9, 2005.)

The primary complication of botulinum toxin A injected into the temporal area is atrophy of the temporal muscles.³⁹ This disuse atrophy is temporary, and patients should be counseled appropriately. Eyelid ptosis is the second most common complication. Some patients have developed antibodies to botulinum toxin A, rendering it relatively ineffective. This has been estimated to occur in over 7% of treated patients.^35,40 The use of non-A botulinum toxins for patients resistant to type A is currently being investigated.³⁵ It should be noted that while the lethal dose is estimated to be very high in humans (the LD50 parenteral dose is 3000 U), the maximum recommended dose is 300-400 U per 3-month period, which minimizes the risk of resistance.³⁵

Frontal triggers

Frontal triggers include any of the glabellar muscles: corrugator supercilii, depressor supercilii, and procerus. The goal of surgery is to prevent further muscular irritation of the supraorbital and supratrochlear nerves, and complete resection is necessary for a favorable outcome.⁴¹ The approach can be either transpalpebral^42,43 or endoscopic. The endoscopic approach can be valuable because a corrugator resection, temporal release, and ZMTBTN resection can all be performed through this approach.

Endoscopic approach

After proper preparation of the face under sedation, the incision sites are marked. There are five total incisions: one midline incision and two on either temple, all placed within the hair-bearing skin. Xylocaine containing 1 : 100 000 epinephrine is injected in the non-hair-bearing skin and xylocaine containing 1 : 200 000 epinephrine is injected in the hair-bearing skin. The dissection is performed in the subperiosteal plane to the supraorbital rim and lateral orbital rim, and zygomatic and malar arches. The procedure for the ZMTBTN is described below, and requires exposure of the zygomatic and malar arches. For corrugator resection, attention is concentrated in the glabellar area. The supraorbital nerves and corrugator muscle are exposed, and the periosteum is then released laterally leaving the central portion intact over the mid-glabellar area to prevent too much resection in the medial eyebrows. The corrugator muscle is removed, and fat harvested from the temporal region is grafted to the corrugator site. Fascial sutures of 3-0 polydioxanone are placed laterally for resuspension. A suction drain is placed in the incision and is fixed with 5-0 plain catgut. Incisions are repaired with 5-0 polygalactin (Vicryl) and 5-0 plain catgut¹ (Fig. 22.4) (see Chapter 7, Forehead rejuvenation).

Fig. 22.4 Endoscopic view of the ZMTBTN. The dissection is performed using a periosteal elevator (A). The nerve can be seen superficial to the deep temporal fascia just under the grasping forceps (B).

Complications

Alopecia can occur at port sites. Temporal or scalp paresthesias or anesthesia can result from this approach, as well as inadequate resection of muscle. Eyebrow elevation can be affected (resulting in either too much or too little elevation uni- or bi-laterally), and dimpling can occur on animation.⁴⁴ The temporal branch of the facial nerve is vulnerable to injury during the dissection, which can result in frontalis paralysis. These complications are rare.

Temporal triggers

Temporal headaches are triggered primarily by contraction the temporal muscle around the ZMTBTN.

After appropriate preparation of the head and face, five 1.5 cm incisions are marked – one midline incision, and two on either temple, 7 cm and 10 cm from the midline. The forehead, temple, and malar regions are then injected with 1% lidocaine with 1 : 100 000 epinephrine; the scalp is injected with 0.5% lidocaine with 1 : 200 000 epinephrine. After the incisions are made with a 15 scalpel, they are deepened with spreading effects of baby Metzenbaum scissors to the deep temporal fascia. The dissection continues using a periosteal elevator until the endoscopic access device (EAD) (Applied Medical Technology, Cleveland, Ohio) is inserted to allow for the endoscope to be introduced. The periosteal elevator then raises periosteum posteriorly and cephalically. Once dissection is completed for the right side, the same is done on the left side. A subperiosteal dissection is then carried under endoscopic visualization to the supraorbital rim, lateral orbital rim, zygomatic, and malar arches. The dissection is continued immediately superficial to the deep temporal fascia and the ZMTBTN is exposed. Grasping forceps are used to hold it while it is avulsed. It is important that as much length of the nerve as possible is transected to prevent re-coaptation, and we usually remove approximately 3 cm. Any bleeding vessels are coagulated and the proximal nerve end is allowed to retract into temporalis muscle to reduce the risk of neuroma formation. The periosteum and arcus marginalis are released in the lateral orbital and supraorbital regions for transposing and fixing the soft tissues.¹ The endoscopic devices are removed, and a single hook is placed on either side of the caudal portion of the incision. A 3-0 PDS suture is used to fix the superficial and intermediate temporal fascia to the deep temporal fascia laterally. A #10 TLS drain is placed, and the skin incisions are repaired with 5-0 poliglecaprone 25 (Monocryl) and 5-0 plain catgut interrupted stitches.

The drain is removed on postoperative day two and the patient is allowed to return to light activities the next day, to regular activities within 7 days, and to heavy activities within 3 weeks.

Occipital triggers

A 4-cm midline incision is designed in hair-bearing caudal occipital region while the patient is seated. After induction of anesthesia, the patient is placed in the prone position with the shoulders raised by a gel roll and the neck flexed. The area around the incision is shaved to approximately 2 cm width. The incision site is then infiltrated with 1% lidocaine with 1 : 100 000 epinephrine. The skin incision is made with a 10 scalpel and hemostasis is achieved with coagulation cautery. The incision is taken to the midline raphe, and the trapezius fascia is incised about 0.5 cm to the right of midline. The semispinalis capitus muscle fibers are identified by their vertical orientation and their location directly underneath the fascia; the trapezius muscle, which rarely reaches the midline, has obliquely oriented fibers, and if encountered it is divided and retracted laterally. The semispinalis muscle is then further exposed using retraction, and dissection continues under the trapezius fascia and muscle laterally. The trunk of the greater occipital nerve is located approximately 1.5 cm from the midline and 3 cm caudal to the occipital protuberance (Point A). Munion clamps are used to isolate the nerve. A full-thickness, 1 inch length of muscle is dissected medially to the nerve, and is transected superiorly and inferiorly using cautery at the coagulation mode. The muscle resection is considered complete when no muscle fibers remain medial to the nerve.

A small portion of the trapezius fascia and muscle immediately overlying the nerve are then removed. The nerve is then isolated with a vessel loop and traced back, ensuring no fascial bands remain. Occasionally, the nerve bifurcates. In this case, it is necessary to remove muscle fibers between the two branches.

A 2 × 2-cm subcutaneously flap based caudally is elevated and passed under the nerve and is sutured to the midline raphe. A drain is placed, and the wound is closed with 5-0 polygalactin (Vicryl) and 5-0 plain catgut. This procedure is then repeated on the other side (Fig. 22.5).

Fig. 22.5 Surgical technique for release of the occipital nerve for occipital migraines. The 4-cm incision is designed in the caudal occipital region (A). The incision is taken to the midline raphe (B) and the trapezius fascia is incised slightly away from the midline (C); the semispinalis muscle fibers can be identified by their vertical orientation. Dissection continues subfascially and superficial to the muscle, and the trunk of the occipital nerve will be seen approximately 1.5 cm lateral to the midline and 3 cm caudal to the occipital protuberance (D). A 1 inch length of muscle is dissected medial to the nerve, and transected (E-G). A flap is designed to be placed under the nerve (H-L). This protects the nerve. The flap is sutured to the midline raphe (M), and a drain is placed (N). The incision is closed in layers while attaching the subcutaneous flap to the midline raphe (O).

The drain is removed in 2 days. The patient is allowed to return to light activity the next day, to routine activity within 1 week, and to heavy activity within 3 weeks.

Septonasal triggers

Septonasal triggers must be considered when injection of botulinum toxin A in other trigger sites results in no change, improvement without resolution, or when the pain is mostly behind the eyes and commonly triggered by weather changes.

The face is prepped and draped after the induction of general anesthesia. The nose is packed with cocaine-soaked gauze and is infiltrated with 0.5% lidocaine with 1 : 200 000 epinephrine initially and 0.5% lidocaine containing 1 : 100 000 epinephrine after a few minutes. An L-shaped incision is made on the left side of the septum, and the mucoperiosteum is elevated. The opposite mucoperiosteum is accessed through an incision in the cartilage and is elevated. The deviated portion of the cartilaginous septum and bone is removed, and a straight piece is replaced. It is crucial to remove any existing spurs and eliminate any contact points between the turbinates and the septum. The mucoperiosteal flaps are sutured back into place with 5-0 chromic running quilting sutures. Doyle splints are placed and fixated with 5-0 prolene sutures.

The Doyle stents are removed in 2 weeks. The patient may resume light activities on postoperative day one and heavy activities on postoperative day seven.

In some cases, the inferior turbinates are enlarged and require resection. The inferior turbinates are infiltrated with 0.5% lidocaine containing 1 : 200 000 epinephrine, and 0.5% lidocaine containing 1 : 100 000 epinephrine after a few minutes. Turbinate scissors are used to resect the inferior turbinates conservatively. A partial infracture is performed and the area is cauterized. A patient who has concha bullosa or significant enlargement of the middle turbinates will require partial or complete resection of the middle turbinates. Using the sharp end of the septal elevator, the mucosa overlying the turbinate is incised and is peeled off over the medial half of the turbinate. The medial wall of the concha bullosa is resected and Doyle stents are inserted.