Orofacial and cephalic pain can arise from a variety of conditions that affect the nerves that supply the head, their roots, and other pain sensitive structures. Trigeminal neuralgia, the prototypical cephalic neuralgia, is characterized by bursts of excruciating facial pain in the distribution of one or more branches of the trigeminal nerve. Chewing, yawning, speaking, and even light touch or a gentle breeze can trigger a single jolt or a flurry. A careful history, physical examination, and diagnostic testing usually reveal underlying or associated conditions. Cranial neuralgias may respond to antiepileptic drugs or various invasive procedures. Pain due to other conditions is best treated by treating the underlying condition.
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• Cranial neuralgias may, more frequently than other headache syndromes, be secondary to central nervous system or peripheral pathology, including carotid artery dissection, arterial venous malformations, aneurysmal dilatation with subsequent compression, etc.
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• For several cranial neuralgias, the diagnostic workup should include structural imaging with MRI with and without contrast to evaluate for evidence of inflammation or space-taking lesions, vascular imaging consisting of either MRA or CTA to evaluate for neurovascular compression, and frequently a laboratory evaluation checking for signs of inflammation (whether autoimmune or related to infection), potentially including cerebrospinal fluid analysis.
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• In as much as secondary causes are found, treating the underlying disorder is considered to be effective in the management of cranial neuralgias. In the absence of a clear secondary cause, we are often left to use treatments proven in other settings for neuropathic pain that may or may not have high quality evidence in this particular genre.
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• Because these disorders were classically challenging to diagnose with no objective findings on examination and because they are frequently associated with psychiatric comorbidities such as depression and anxiety, they have often been mischaracterized as being purely psychiatric in nature and may carry stigmata for patients and their families.
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• As many of these syndromes tend to be refractory to treatment and may persist for years without spontaneous remission, there is a high degree of associated disability, and many patients undergo multiple unnecessary procedures in an attempt to relieve their pain, which may lead to additional problems henceforth.
Historical note and terminology
Trigeminal neuralgia. The first known description of trigeminal neuralgia, was written in the second century AD by Aretaeus of Cappadocia, a contemporary of Galen. Also known for his descriptions of migraine, he makes reference to a pain in which spasm and distortion of facial expression take place. Jujani, an 11th century Arab physician, mentions in his writings unilateral facial pain causing spasms and anxiety. Interestingly, he suggests that the cause of the pain is “the proximity of the artery to the nerve.” The first full account of trigeminal neuralgia was published in 1773 when John Fothergill presented a paper to the Medical Society of London. He described the classic trigeminal neuralgia, including paroxysms of unilateral facial pain, evoked by eating or speaking or touch, starting and ending abruptly, and associated with anxiety. Some time earlier, Nicolaus André had used the term “tic douloureux” to describe a similar entity. Later observations in the 18th and 19th centuries by Pujol, Chapman, and Tiffany helped to differentiate trigeminal neuralgia from other common facial pains.
In the early 20th century, Oppenheim alluded to an association between multiple sclerosis and trigeminal neuralgia.
Modern neurosurgical treatment can be traced back to 1925 when the concept of vascular decompression was introduced; however, it was at least 50 years later that microvascular decompression gained wide‐spread acceptance as a treatment method. Gardner and Miklos promoted the theory and modified the technique further in the 1950s and 1960s. It was not until the large case series published in 1970s by Jannetta that a major shift in neurosurgical practice began to appear. Neuroablative procedures kept evolving throughout the century, with attempts to balance the adverse effects of neural injury with sufficient pain control.
Pharmacotherapy had little success in this condition until Bergouignan’s discovery in 1942 that phenytoin was effective in preventing pain paroxysms. Soon, following the introduction of carbamazepine for treatment of epilepsy, controlled trials were published showing its superiority over placebo in trigeminal neuralgia. Since then, anticonvulsants have remained the mainstay of pharmacological treatment (119).
Glossopharyngeal neuralgia. The first description of glossopharyngeal neuralgia is credited to Theodore H Weisenburg in 1910. His patient presented with the classical symptoms of lancinating pain in the ear and neck, which on autopsy 6 years later were identified as secondary to an underlying cerebellopontine angle tumor, which compressed the trigeminal nerve and stretched the glossopharyngeal nerve.
Ten years later, Sicard and Robineau described 3 patients who had “algie velo-pharyngee essentielle” (pain in the distribution of the glossopharyngeal nerve of unknown cause). These patients failed treatment with pharmacotherapy and sedatives and then underwent a resection of the glossopharyngeal nerve with subsequent pain relief.
A year later, Wilfred Harris coined the term “glossopharyngeal neuralgia,” as it resembled classic trigeminal neuralgia in the severity and suddenness of onset, brevity, and duration (127).
Working separately in 1910, Weisenburg established glossopharyngeal neuralgia as a clinical entity, distinct from trigeminal neuralgia, with which it was often confused. Furthermore, two so-called variants have been described: an otitic form with pain mainly deep in or near the ear and an oropharyngeal form with the pain in the pharynx, tonsil, soft palate, and back of the tongue (127).
Nervus intermedia neuralgia. Nervus intermedius neuralgia, also known as geniculate neuralgia, is an extremely rare form of a cranial neuralgia. The nervus intermedius nerve was first identified in 1563 and also has been known as the intermediary nerve, intermediate nerve, geniculate ganglionitis, or Wrisberg’s nerve. Professor Heinrich August Wrisberg described the nerve in detail and in 1777 named it “portio media inter comunicantem faciei et nervum auditorium.” In 1857, John Nottingham introduced the term “tic douloureux of the ear” to describe the sudden paroxysms of pain accompanied by flushing of the auricle. In 1907, Ramsay Hunt noted cutaneous manifestations of patients with herpes zoster of the ear. He described the “zone of Ramsay Hunt” that correlated to the innervation from the nervus intermedius. The “tic douloureux of the ear” became known as geniculate neuralgia (08; 27).
Occipital neuralgia. Occipital neuralgia, or Arnold neuralgia, was first described in 1821 as recurrent headaches localized in the occipital region (28).
Tolosa-Hunt syndrome. Tolosa-Hunt syndrome is a rare, granulomatous inflammatory disorder presenting with a unilateral severe headache followed by or simultaneously occurring with very painful and restricted eye movements. It is recognized by the National Organization for Rare Disorders and was first described in 1954 by the Spanish neurosurgeon Dr. Edward Tolosa (118). He described a patient who had orbital pain in the left area, ipsilateral ophthalmoplegia, significant loss of visual acuity, and hypoesthesia in the first branch of the trigeminal nerve. Autopsy revealed granulomatous inflammation of the cavernous sinus. A few years later, in 1961, William Hunt and his coworkers presented the first report in the American literature of a syndrome characterized with similar signs and symptoms (77). Finally, in 1966 Smith and Taxal were the first authors to describe this collection of signs and symptoms as the Tolosa Hunt Syndrome. They had encountered similar cases that previously had been given alternative diagnoses; however, given these symptoms and the dramatic response to systemic steroid therapy, they realized that this is a definite clinical entity (144). Since this syndrome was coined, there have been numerous cases and studies reported around the world (11). The exact etiology is unclear, although it shares histopathological features with idiopathic orbital pseudotumor (107).
Raeder syndrome. Raeder syndrome was first described in 1918 by the Norwegian ophthalmologist George Raeder and later extended by the same author. One of the first cases in the Norwegian Magazine of Medical Science described an 18-year-old male patient with left eye, temple, and occipital pain as well as miosis of the left pupil and left jaw deviation. This particular patient eventually was found to have a middle cranial fossa tumor contributing to this syndrome; however, since then many idiopathic cases have been reported that often have a self-limited course.
In the 1950s, Boniuk and Schlezinger further subdivided the Raeder syndrome into Groups 1 and 2. Group 1 involved patients such as those described above with oculosympathetic paresis and trigeminal and potentially other cranial nerve involvement. Group 2 patients consisted of those with painful postganglionic Horner syndrome who often had a more benign and self-limited course that lasted few weeks.
Later, Mokri drew attention to the fact that an internal carotid artery dissection can often cause painful postganglionic Horner syndrome as well (139).
Thus, Raeder syndrome, also known as the paratrigeminal syndrome, can be subdivided into groups. The first group, Group IA, has primary trigeminal, oculomotor, or other cranial nerve involvement; this group typically requires a thorough neuroradiologic or diagnostic work up and usually carries a poor long-term prognosis. The second group, Group IB, has no oculomotor involvement and usually experiences a much better outcome. Group II is typically a painful postganglionic Homer syndrome with a self-limited course and excellent prognosis (139).
Burning mouth syndrome. Although medical science has been aware of burning mouth syndrome for more than a century, it was not formally categorized as a distinct headache disorder until the ICHD-2 was released in 2004 (156).
Idiopathic facial pain. Prior to adopting formal diagnostic criteria, persistent idiopathic facial pain included many variants that were considered atypical of trigeminal neuralgia as well as migraine. As a result, a wide variety of patients over the years have been considered to have persistent idiopathic facial pain (26).