Neuroanatomy, Semilunar Ganglion

Structure and Function

The semilunar ganglion is a crescent-shaped structure located at the anterior, inferior, and lateral borders of Meckel’s cave, a dural recess formed between the dura propria and periosteal dura of the middle cranial fossa.[3] It acts as a conduit between the middle and posterior fossae, which connects the prepontine cistern and the cavernous sinus.[4] Meckel’s cave is situated within the trigeminal impression at the petrous apex of the temporal bone and is in close proximity to the carotid canal inferolaterally, and its upper anterior part borders the fibrous lateral wall of the cavernous sinus.[4][5][4] A further important relationship is with the superior petrosal sinus, which passes directly over the trigeminal ganglion within Meckel’s cave.[6] The cave is thus a dural space that contains the semilunar (trigeminal) ganglion.

The convex border of the semilunar ganglion is located at the antero-infero-lateral walls of Meckel’s cave, while the concave border, which is also known as the sinus ganglion, is located postero-supero-medially in the direction of the trigeminal cistern and the ostium of Meckel’s cave. A layer of dura propria and arachnoid surrounds the semilunar ganglion. The posteromedial portion of the semilunar ganglion is situated in the trigeminal cistern while the anteroinferior portion is located outside of the trigeminal cistern as it adheres closely to the dura of the Meckel’s cavity medially, and the dura of the temporal fossa laterally.[1]

The semilunar ganglion segregates into three divisions: the ophthalmic (V1), which is the dorsal division, maxillary (V2), which is the intermediate portion, and the mandibular (V3), which is the ventral division. The ophthalmic portion exits the semilunar ganglion and enters the orbit via the superior orbital fissure. It separates into the supraorbital, supratrochlear, and nasociliary nerves that provide innervation to the nose and forehead. The maxillary portion leaves the middle cranial fossa by passing through the foramen rotundum before branching multiple times to provide innervation via the infraorbital, palatine, zygomatic, and superior alveolar nerves.[7] The mandibular division exits the cranium through the foramen ovale and separates into the buccal, auriculotemporal, lingual, and inferior alveolar nerves (see Image. Foramen Ovale).[8] It is the only division of the trigeminal nerve that provides both sensory and motor components.

The cellular composition of the semilunar ganglion is between 20,000 to 35,000 pseudo-unipolar neurons, with non-neuronal cells, such as glia and fibroblasts, outnumbering them by approximately 100 times.[9]

The semilunar ganglion is essential for releasing many neuropeptides and signaling molecules. As a potent vasodilator, calcitonin gene-related peptide is the most prevalent among these neuropeptides and plays a vital role in the pathophysiology of cluster and migraine headaches.[10] The semilunar ganglion also expresses many signaling molecules, including adenosine triphosphate, neurotrophic factors, nitric oxide, and cytokines, that target nearby neurons or satellite glial cells. These signaling molecules and neurotrophic factors play an important role in peripheral and central sensitization, such as in the case of primary headaches.[2]

Embryology

The semilunar ganglion contains neurons that arise from two trigeminal placodes and the neural crest. In the chick, they are known as the ophthalmic and maxillomandibular trigeminal placodes, whereas in the Xenopus frog, they are known as the profundal and trigeminal placodes. In the chick, the ophthalmic placode has a small area of ectodermal thickenings divided across a broad area rostral to rhombomere one and gives rise to postmitotic neurons.[11] The maxillomandibular placode is a much thicker area of ectodermal thickenings that is ventral to rhombomeres two and three and gives rise to mitotically active neurons.[12] 

The first condensation of the semilunar ganglion forms by neural crest cells. In the chick, the ophthalmic placode can express Pax3 (also known as the paired domain transcription factor gene), Fgfr4, (also known as the fibroblast growth factor receptor 4 gene), and Neurogenin2 (also known as the proneural transcription factor gene) while the maxillomandibular trigeminal placode expresses Ngn1 (also known as the proneural transcription factor gene). Neurogenesis in the ophthalmic placode starts in the ten-somite stage with the expression of Ngn2. Researchers also found that even though the degree of separation between the ophthalmic and maxillomandibular trigeminal placodes augments with time, a definitive border between them does not exist even at the 16-somite level. Moreover, some cells along the border between the two placodes express Pax3 and Ngn1, which suggests these cells respond to ophthalmic and maxillomandibular placode-inducing signals.[12]

Blood Supply and Lymphatics

Blood supply to the semilunar ganglion comes from the middle meningeal artery, accessory middle meningeal artery, the inferolateral trunk of the internal carotid artery, and the tentorial branch of the superior cerebellar artery. The trigeminal nerve root acquires vascular supply from the superolateral pontine artery, anterior inferior cerebellar artery, inferolateral or posterolateral pontine arteries, superior cerebellar artery, basilar artery, and trigeminocerebellar artery. The motor root and the ophthalmic portion of the sensory root usually receive blood supply from the superolateral pontine artery while the maxillary portion receives blood supply from the superolateral and inferolateral pontine arteries and the mandibular portion of the anterior inferior cerebellar artery. Most of the blood supply to the semilunar ganglion is supplied by the middle meningeal artery and inferolateral trunk of the internal carotid artery.[13]

As discussed previously, the superior petrosal sinus lies in close proximity to Meckel's cave and provides venous drainage of the cavernous sinus. It passes posterolaterally from this point to drain into the junction of the sigmoid and transverse sinuses.[6] It runs in the superior petrosal sulcus of the petrous part of the temporal bone, adjacent to the trigeminal impression, in which the semilunar ganglion lies within Meckel's cave.

Muscles

Only the mandibular branch of the trigeminal nerve has a motor component. The mandibular branch provides motor innervation to the facial muscles involved in mastication, including the master, temporalis muscle, and lateral and medial pterygoids.[14] It also separates into branches that innervate the tensor tympani, tensor vela palatine, mylohyoid, and the anterior part of the digastric muscle.[15] Masticatory weakness is a recognized complication following percutaneous balloon compression or ablation of the semilunar ganglion, albeit occurring at a relatively low rate. It has been reported to present in around 1% of patients following percutaneous balloon compression and typically resolves in the follow-up period over some weeks.[16]

Physiologic Variants

Reports indicate that the size of the semilunar ganglion varies from 14 to 22 mm in length and 4 to 5 mm in thickness. However, after taking into account the concave structure of the semilunar ganglion, the semilunar ganglion is 1.5 to 2 mm in thickness.[1]

Surgical Considerations

Targeting the semilunar ganglion in Meckel’s cave by utilizing anatomic landmarks or image-guided by fluoroscopy or computed tomography may be effective for patients with refractory facial pain due to trigeminal neuralgia, certain headaches, conditions such as recalcitrant herpes zoster ophthalmicus and postherpetic neuralgia. This option is generally considered when medical management with maximal oral analgesia (typically carbamazepine) has been trialed and not provided adequate pain relief. The procedure may also be an option in cases where neurosurgical management is not practical.

The procedure was first described by Belber et al. in 1987 [17] and has since become widely accepted as safe and efficacious in treatment-resistant trigeminal neuralgia.[18][19] The procedure involves access via the mouth with a needle to enter the foramen ovale and, therefore, Meckel’s cave (see Image. Foramen Ovale, Computed Tomography). The patient is placed in the supine position at 30 degrees, and intraoperative fluoroscopy is used to confirm the successful placement of the cannula.[19] The Hartel anatomical landmarks are used: the entry point through the skin is 2.5cm lateral from the angle of the mouth, with a trajectory towards the medial border of the ipsilateral pupil, intersecting a line approximately 2.5cm anteriorly from the external auditory meatus.[20] 

Once access is gained, either balloon compression, glycerol infiltration, or radiofrequency thermocoagulation of the semilunar ganglion can be performed to provide a therapeutic effect.[21][22][23][22][21] Meta-analysis of the different techniques shows that all three techniques are largely equal with regard to their ability to provide pain relief.[24][25] However, some of the post-operative risks are more nuanced. Patients undergoing balloon compression were found to be at higher risk of post-operative mastication weakness and trochlear nerve weakness (see Image. Trochlear Nerve, Nerves of the Orbit).[26] Patients undergoing radiofrequency ablation, however, were found to have increased rates of post-operative trigeminal anesthesia but, conversely, lower rates of herpes reactivation.[26]  Although providing a significantly less-invasive option for treating trigeminal neuralgia, the three percutaneous techniques do not offer significantly reduced complication rates compared to the more invasive operative technique of microvascular decompression.[27][28]

Clinical Significance

As stated previously, the semilunar ganglion plays a critical role in expressing various neuropeptides and signaling molecules that are important in gene expression, modulation of sensory information, and peripheral and central sensitization.[29] As a potent vasodilator, calcitonin gene-related peptide is the most prevalent among these neuropeptides and plays an essential role in the pathophysiology of cluster headaches.[2][30] The semilunar ganglion also expresses many signaling molecules, including adenosine triphosphate, neurotrophic factors, nitric oxide, and cytokines, that target nearby neurons or satellite glial cells.[10]

The semilunar ganglion is also known to become latently infected with the herpes simplex virus type-1 (HSV-1).[31] HSV-1 would periodically reactivate, whereas the varicella-zoster virus rarely reactivates itself. The reactivation of this virus generally results in various cranial nerve disorders, including vestibular neuritis, Bell’s palsy, and herpes labialis. Also, as stated previously, neural block of the semilunar ganglion may be effective for patients with refractory facial pain, certain headaches, and other conditions, such as recalcitrant herpes zoster ophthalmic and postherpetic neuralgia who have not responded well to other means. The semilunar ganglion also is involved in the often underappreciated perineural spread of tumors, which are the most common malignant tumors in which there is delayed diagnosis. This situation is a well-recognized phenomenon in head and neck cancers, including squamous cell carcinoma, adenocystic carcinoma, lymphoma, and rhabdomyosarcoma.[14]

The semilunar ganglion is also known to incur damage in patients with the trigeminal trophic syndrome (TTS).[32] Commonly seen in elderly patients, TTS is a form of chronic facial ulceration that usually appears in a unilateral crescent-shaped form near the nasal ala and, in more serious cases, in the jaw, forehead, cheeks, and lips. Patients with TTS may report paraesthesia, including burning or shooting pains. The general belief is that ulceration might result from the patient touching their face consistently, especially during sleep. Some treatment options include altering the patient’s behavior, occlusive dressings, oral psychotropic medications, and arm splints.[32]