Influence of lamotrigine over the sunct syndrome: one patient follow-up for two years

Piovesan, Elcio Juliato; Siow, Charles; Kowacs, Pedro Andre; Werneck, Lineu Cesar

doi:10.1590/S0004-282X2003000400032

Abstracts

The SUNCT syndrome is characterized by a short-lasting headache in the first division of the trigeminal nerve, associated with ipsilateral autonomic symptoms. It is highly refractory to prophylactic medication. We describe a case where lamotrigine reduced the intensity, duration, and frequency of attacks and increased the remission period of this disorder. Over a two-year period, the attacks came back immediately whenever the patient reduced the dose or neglected treatment. We concluded that lamotrigine is effective in treating SUNCT syndrome when used in high doses for a prolonged period of time.

lamotrigine; prophylactic treatment; SUNCT syndrome; trigeminal autonomic cephalalgia

A sindrome SUNCT caracteriza-se por cefaléia de curta duração localizada na primeira divisão do nervo trigêmio e associada com sintomas autonômicos ipsilaterais. A resposta clínica aos diversos tratamentos profiláticos propostos têm sido caracterizados pela alta refratoriedade. Nós descrevemos um caso em que a lamotrigina reduziu a intensidade, duração e frequência dos ataques, aumentando o período de remissão. Por um período de dois anos em que utilizamos a lamotrigina, surgiram novos ataques quando o paciente reduziu a dose ou negligenciou o seu tratamento.Concluímos que lamotrigina é tratamento eficaz para a síndrome SUNCT quando utilizada em altas doses e por período prolongado de tempo.

cefaléias trigemino-autonomicas; lamotrigina; SUNCT sindrome; tratamento profilático

Influence of lamotrigine over the sunct syndrome: o ne patient follow-up for two years. Case report

Influência da lamotrigina sobre a síndrome SUNCT: comportamento de um paciente durante período de dois anos

Elcio Juliato Piovesan^{I, II, III}; Charles Siow^II; Pedro Andre Kowacs^I; Lineu Cesar Werneck^I

^IHeadache Unit, Neurology Division, Internal Medicine, Hospital de Clinicas da Universidade Federal do Parana, Curitiba, PR, Brazil

^IIJefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA, USA

^IIIHeadache Center Research Laboratory, Department of Neurology, Thomas Jefferson University, Philadelphia, PA

ABSTRACT

The SUNCT syndrome is characterized by a short-lasting headache in the first division of the trigeminal nerve, associated with ipsilateral autonomic symptoms. It is highly refractory to prophylactic medication. We describe a case where lamotrigine reduced the intensity, duration, and frequency of attacks and increased the remission period of this disorder. Over a two-year period, the attacks came back immediately whenever the patient reduced the dose or neglected treatment. We concluded that lamotrigine is effective in treating SUNCT syndrome when used in high doses for a prolonged period of time.

Key words: lamotrigine, prophylactic treatment, SUNCT syndrome, trigeminal autonomic cephalalgia.

RESUMO

A sindrome SUNCT caracteriza-se por cefaléia de curta duração localizada na primeira divisão do nervo trigêmio e associada com sintomas autonômicos ipsilaterais. A resposta clínica aos diversos tratamentos profiláticos propostos têm sido caracterizados pela alta refratoriedade. Nós descrevemos um caso em que a lamotrigina reduziu a intensidade, duração e frequência dos ataques, aumentando o período de remissão. Por um período de dois anos em que utilizamos a lamotrigina, surgiram novos ataques quando o paciente reduziu a dose ou negligenciou o seu tratamento.Concluímos que lamotrigina é tratamento eficaz para a síndrome SUNCT quando utilizada em altas doses e por período prolongado de tempo.

Palavras-chave: cefaléias trigemino-autonomicas, lamotrigina, SUNCT sindrome, tratamento profilático.

Shortlasting, unilateral, neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome) was first described by Sjaastad 25 years ago¹. During this period, some new clinical evidences were included in the spectrum of this syndrome, but our knowledge of this disorder is constantly advancing.

We describe a case responsive to lamotrigine and review the current literature on SUNCT.

CASE

A 45-year-old man had a five-year history of severe shooting pain over the left eye that lasted 30 seconds and occured as often as 20 times a day. These symptoms were accompanied by intense ipsilateral tearing, conjunctival injection, and nasal congestion. Attacks could be provoked by touching the left temporal region, putting his foot on the ground, eating, or moving his neck. General physical and neurologic examinations, routine blood analysis, and CT and MRI of the brain were normal. The patient tried indomethacin 200mg/day, verapamil 480mg/day, carbamazepine 1200mg/day, phenytoin 300mg/day, valproate 1000mg/day, and greater occipital and supraorbital blocker with bupivacaine and steroids, all without effect. During the attacks, he used oxygen and triptans but had poor results. The patient also had thermocoagulation of the ipsilateral trigeminal ganglion performed. He had a good result and was symptom-free for two years, but the attacks then returned. Methysergide 4mg/day and celecoxib 300mg/day partially relieved the headache but these medications had to be discontinued as the patient showed significant side effects.The patient was subsequently tried on lamotrigine, with the dose being increased by 50mg every 10 days until a total dose of 300mg/day was reached. There was continued improvement. He had no new headaches for five months, at which time the lamotrigine was tapered to 100mg/day and the attacks returned at the rate of 10 attacks per day. Lamotrigine was increased to 300mg/day and the attacks were eliminated after 45 days. On one occasion, the patient neglected to take his medication for one week. The attacks returned and only disappeared 30 days after reintroducing the medication. We have followed this patient for more than eight months. He has been on adequate dose of lamotrigine and has had no new attacks.

DISCUSSION

SUNCT syndrome is one of a number of trigeminal autonomic cephalalgias characterized by short-lasting headache occurring in the first division of the trigeminal nerve^2,3. The pain is maximal in and around the eye and may radiate to the ipsilateral forehead, temple, nose, cheek, and palate⁴. Attacks are typically unilateral, although in some cases the pain also simultaneously occurred on the opposite side⁴. The pain is usually burning, stabbing, or electrical in nature⁴. The paroxysms begin and end abruptly, reaching maximum intensity within 2 to 3 seconds⁴. The pattern of solitary attacks is usually "plateau-like" but other patterns, such as "repetitive", "saw-toothlike", and "plateau-like plus exacerbations" have been noted⁵. Individual headache attacks last between 5 and 250 seconds each (mean 49 seconds)⁶; attacks lasting 2 hours have also been described⁷. A dull interictal discomfort may or may not persist between acute episodes^7,8. Four patients experienced a "status-like" pattern, in which painful paroxysms persisted for 1 to 3 days⁹.

The temporal pattern is also quite variable, with symptomatic periods alternating with periods of pain-free remissions in an erratic fashion. Symptomatic periods generally last from a few days to several months and occur once or twice yearly. Remissions range from 1 week to 7 years but usually are of several months' duration^4,7. A bimodal distribution with increased attack frequency occurring in the morning and afternoon/evening hours has been described⁶, and nocturnal attacks can occur⁴. During symptomatic phases, attacks may be precipitated by a variety of triggers located within trigeminal and/or extra-trigeminal areas. Precipitants include touching the hair, forehead, face, nose, and lip on the symptomatic side. Washing, shaving, eating, chewing, tooth-brushing, talking, and coughing were also reported as headache triggers⁴. Mechanical movements of the neck can also precipitate attacks, and in some cases abort them^2,4. Our patient related that his paroxysms were triggered when he touched his foot over the ground, touched the temporal region, ate, or moved his neck.

The acute attacks are accompanied by ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhea, and eyelid edema⁸. In some patients, autonomic symptoms were bilateral, although more pronounced on the side of the headache⁴. The associated tearing and conjunctival injection usually begins 1 to 2 seconds following the acute episodes of pain and may persist for a few seconds longer than the painful episodes⁴. The symptoms can remain 30 to 60 seconds following headache resolution^2,10, and in rare cases until 10 minutes post resolution¹¹.

Most cases occur in men⁴ (male:female ratio 17:2)⁵; the age of onset ranges from 23 to 77 years (mean 51 years)⁴. The etiology is unknown, but recently cases secondary to cerebellopontine angle arteriovenous malformations^12,13, brain stem cavernous hemangioma¹⁴, a posterior fossa lesion in a patient with AIDS³, prolactinomas¹⁵, and corneal lesion¹⁶ have been described.

Excluding symptomatic cases, CT, MRI, and angiography, when performed, were essentially normal. In some cases, orbital phlebography reveals a narrowed superior ophthalmic vein ipsilateral to the headache¹⁷. Ipsilateral Intraocular pressure and corneal temperatures are increased, as is forehead sweating, during attacks^17,18, but pupillometry and pharmacologic studies of the pupil are normal¹⁹. Single photon emission computed tomography and transcranial doppler studies are normal during attacks^20,21. One patient with SUNCT syndrome had activation in the posterior hypothalamic grey on functional MRI during one attack²². These findings demonstrate for the first time that a central nervous system dysfunction may be involved in the pathophysiology of SUNCT.

SUNCT syndrome is, perhaps, the most refractory of all primary headache disorders. Rare cases are responsive to gabapentin^23-25, topiramate²⁶, carbamazepine⁴, corticosteroids, or surgical procedures²⁷. Some cases did not improve after surgical treatment, and there was significant morbidity²⁸. Verapamil and omeprazole were reported to worsen the headache²⁹. Nonsteroidal anti-inflammatory drugs and tricyclic antidepressants showed minimal effect²⁹. Lamotrigine, a new antiepileptic drug used for treating other painful neurologic syndromes^30-32, has shown good results in the treatment of SUNCT syndrome^33-37. Lamotrigine acts by stabilizing the neuronal sodium channel³⁸, which suppress the excessive release of glutamate. As a potent antiglutamatergic drug, it is involved in the N-methyl-D-aspartic acid neurotransmitter, which acts on the antinociceptive pathway responsible for the establishment of chronic pain³⁹. Lamotrigine also reduced pain behavior in a rat model of neuropathic pain^40-41.

By beginning with low doses and gradually increasing, side effects such as skin rash can be avoided (there is a case report of a fatal outcome with this skin rash)⁴². Lunardi et al report that when lamotrigine is used in trigeminal neuralgia there is a direct relationship between daily dose, plasma level of lamotrigine, and analgesic effect; this study shows that pain relief is proportional to the daily dosage and to drug plasma levels, with the maximum daily dosage used being 400mg⁴³. This effect on the SUNCT syndrome was observed in our case and in the recent papers³⁷.

In our case, the temporal pattern changed after the patient was started on lamotrigine. The initial dose of 100mg reduced the number of SUNCT attacks from 30 per day to 10 per day. When we increased the dose to 300mg/day (100mg tid), the attacks progressively reduced until they finally disappeared. After this initial response, the patient relapsed on three occasions: once because he neglected to take the medication and twice because he reduced the dose. After reintroducing the medicine, the attacks continued for two more weeks, reducing progressively in the next two weeks until they disappeared. During these periods, the patient used different analgesics, triptans, NSAIDS, codeine and corticosteroids with poor results. A block of the greater occipital and supraorbital nerves with corticosteroids and bupivacaine was also futile.

Here we see the influence of lamotrigine on the behavior of the attacks and probably over the cyclical pattern. The etiology of SUNCT syndrome may be related to the posterior hypothalamic grey²², thereby explaning its cyclical behavior. Lamotrigine improved the headache and induced a change in the cyclical behavior. During lamotrigine reintroduction, the pain did not abate, which showed us that the subsequent action of the drug is more gradual.

Our patient that has used lamotrigine for two years, and it has reduced the intensity, duration and frequency of the SUNCT attacks, and has kept the patient asymptomatic for a longer time. To induce a remission, the patient required a high dose of lamotrigine (300mg/day) and treatment of at least 2 weeks or more.

Received 10 December 2002, received in final form 12 March 2003

Accepted 20 March 2003

Dr. Elcio Juliato Piovesan - Rua Jorge Manços do Nascimento Teixeira 868 - 83005-500 São José dos Pinhais PR - Brasil.

1. Sjaastad O, Russell D, Horven I, Bunaes U. Multiple neuralgiform unilateral headache attacks associated with conjunctival injection and appearing in clusters: a nosological problem. Proc Scand Migraine Soc 1978;31.
2. Sjaastad O, Saunte C, Salvesen R, et al. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhea. Cephalalgia 1989;9:147-156.
3. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic features, including new cases. Brain 1997;120:193-209.
4. Pareja JA, Sjaastad O. SUNCT syndrome: a clinical review. Headache 1997;37:195-202.
5. Pareja JA, Sjaastad O. SUNCT syndrome in the female. Headache 1994;34:217-220.
6. Pareja JA, Shen JM, Kruszewski P, Caballero V, Pamo M, Sjaastad O. SUNCT syndrome: duration, frequency, and temporal distribution of attacks. Headache 1996;36:161-165.
7. Pareja JA, Joubert J, Sjaastad O. SUNCT syndrome: atypical temporal patterns. Headache 1996;36:108-110.
8. Newman LC. Effective management of ice pick pains, SUNCT, and episodic and chronic paroxysmal hemicrania. Curr Pain Headache Rep 2001;5:292-299.
9. Pareja JA, Caballero V, Sjaastad O. SUNCT syndrome: statuslike pattern. Headache 1996,36:622-624.
10. Becser N, Berky M. SUNCT syndrome: a Hungarian case. Headache 1995;35:158-160.
11. Hannerz J, Greitz D, Hansson P, Ericson K. SUNCT may be another manifestation of orbital venous vasculitis. Headache 1992;32:384-389.
12. Bussone G, Leone M, Dalla Volta G, Strada L, Gasparotti R, DiMonda V. Short-lasting unilateral neuralgiform headache attacks with tearing and conjunctival injection: the first "symptomatic" case? Cephalalgia 1991;11:123-127.
13. De Benedittis G. SUNCT syndrome associated with cavernous angioma of the brain stem. Cephalalgia 1996;16:503-506.
14. Morales F, Mostacero E, Marta J, Sanchez S. Vascular malformation of the cerebellopontine angle associated with "SUNCT" syndrome. Cephalalgia 1994;14:301-302.
15. Massiou H, Launay JM, Levy C, El Amrani M, Emperauger B, Bousser MG. SUNCT syndrome in two patients with prolactinomas and bromocriptine-induced attacks. Neurology 2001;58:1698-1699.
16. Piovesan EJ, Kowacs PA, Werneck LC. SUNCT syndrome: report of a case preceded by ocular trauma. Arq Neuropsiquiatr 1996;54:494-497.
17. Kruszewski P. Shortlasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome): V. Orbital phlebography. Cephalalgia 1992;12:387-389.
18. Sjaastad O, Kruszewski P, Fostad K, Elsas T, Ovigstad G. SUNCT syndrome: VII. Ocular and related variables. Headache 1992;32:489-495.
19. Zhao JM, Sjaastad O. SUNCT syndrome: VIII. Pupillary reaction and corneal sensitivity. Func Neurol 1993;8:409-414.
20. Shen JM, Johnsen HJ. SUNCT syndrome: estimation of cerebral blood flow velocity with transcranial Doppler ultrasonography. Headache 1994;34:25-31.
21. Poughias L, Aasly J. SUNCT syndrome: cerebral SPECT images during attacks. Headache 1995;35:143-145.
22. May A, Bahra A, Buchel C, Turner R, Goadsby PJ. Functional magnetic resonance imaging in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 1999;46:791-794.
23. Graff-Radford SB. SUNCT syndrome responsive to gabapentin (neurotin). Cephalalgia 2000;20:515-517.
24. Porta-Etessam J, Benito-Leon J, Martinez-Salio A, Berbel A. Gabapentin in the treatment of SUNCT syndrome. Headache 2002;42:523-524.
25. Hunt CH, Dodick DW, Bosch EP. SUNCT responsive to gabapentin. Headache 2002;42:525-526.
26. Matharu MS, Boes CJ, Goadsby PJ. SUNCT syndrome: prolonged attacks, refractoriness and response to topiramate. Neurology 2002;58:1307.
27. Pareja JA, Caminero AB, Sjaastad O. SUNCT syndrome: diagnosis and treatment. CNS Drugs 2002;16:373-383.
28. Black DF, Dodick DW. Two cases of medically and surgically intractable SUNCT: a reason for caution and an argument for a central mechanism. Cephalalgia 2002;22:201-204.
29. Pareja JA, Kruszewski P, Sjaastad O. SUNCT syndrome: trial of drugs and anesthetic blockades. Headache 1995;35:138-142.
30. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, Patton DW, Mullens EL. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain 1997;73:223-230.
31. Casey KL. Pain and central nervous system disease: the central pain syndromes. New York: Raven 1991.
32. Canavero S, Bonicalzi V. Lamotrigine control of central pain. Pain 1996;68:179-181.
33. D'Andrea G, Granella F, Cadaldini M. Possible usefulness of lamotrigine in the treatment of SUNCT syndrome. Neurology 1999;53:1609.
34. Leone M, Rigamonti A, Usai S, Damico D, Grazzi L, Bussone G. Two new SUNCT cases responsive to lamotrigine. Cephalalgia 2000;20:845-847.
35. D'Andrea G, Granella F, Ghiotto N, Nappi G. Lamotrigine in the treatment of SUNCT syndrome. Neurology 2001;72:866-871.
36. Tilignac C, Dordain G. SUNCT syndrome sensitive to lamotrigine. Presse Med 2001;30:1106.
37. Gutierrez-Garcia JM. SUNCT syndrome responsive to lamotrigine. Headache 2002;42:823-825.
38. Xie X, Lancaster B, Peakman T, Garthwaite J. Interaction of the antiepilelptic drug lamotrigine with recombinant rat brain type IIA Na⁺ channels and with native Na⁺ channels in rat hippocampal neurones. Pflugers Arch 1995;430:437-446.
39. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293-299.
40. Nakamura-Craig M, Follenfant RL. Lamotrigine and analgesia: a new treatment for chronic pain? In Gebhart GF, Hammond DL, Jensen TS. (eds) Progress in pain research and treatment, vol 2 Seattle: IASP Press, 1994:725-730.
41. Nakamura-Craig M, Follenfant RL. Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE₂ and in the chronic hyperalgesia in rats with streptozocin-induced diabetes. Pain 1995;63:33-37.
42. Sterker M, Berrouschot J, Schneider D. Fatal course of toxic epidermal necrolysis under treatment with lamotrigine. Int J Clin Pharmacol Ther 1995;33:595-597.
43. Lunardi G, Leandri M, Albano C, et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 1997;48:1714-1717.

Publication Dates

Publication in this collection
16 Sept 2003
Date of issue
Sept 2003

History

Accepted
20 Mar 2003
Reviewed
12 Mar 2003
Received
10 Dec 2002

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Sjaastad O, Russell D, Horven I, Bunaes U. Multiple neuralgiform unilateral headache attacks associated with conjunctival injection and appearing in clusters: a nosological problem. Proc Scand Migraine Soc 1978;31.

[2] 2. Sjaastad O, Saunte C, Salvesen R, et al. Short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing, sweating, and rhinorrhea. Cephalalgia 1989;9:147-156.

[3] 3. Goadsby PJ, Lipton RB. A review of paroxysmal hemicranias, SUNCT syndrome and other short-lasting headaches with autonomic features, including new cases. Brain 1997;120:193-209.

[4] 4. Pareja JA, Sjaastad O. SUNCT syndrome: a clinical review. Headache 1997;37:195-202.

[5] 5. Pareja JA, Sjaastad O. SUNCT syndrome in the female. Headache 1994;34:217-220.

[6] 6. Pareja JA, Shen JM, Kruszewski P, Caballero V, Pamo M, Sjaastad O. SUNCT syndrome: duration, frequency, and temporal distribution of attacks. Headache 1996;36:161-165.

[7] 7. Pareja JA, Joubert J, Sjaastad O. SUNCT syndrome: atypical temporal patterns. Headache 1996;36:108-110.

[8] 8. Newman LC. Effective management of ice pick pains, SUNCT, and episodic and chronic paroxysmal hemicrania. Curr Pain Headache Rep 2001;5:292-299.

[9] 9. Pareja JA, Caballero V, Sjaastad O. SUNCT syndrome: statuslike pattern. Headache 1996,36:622-624.

[10] 10. Becser N, Berky M. SUNCT syndrome: a Hungarian case. Headache 1995;35:158-160.

[11] 11. Hannerz J, Greitz D, Hansson P, Ericson K. SUNCT may be another manifestation of orbital venous vasculitis. Headache 1992;32:384-389.

[12] 12. Bussone G, Leone M, Dalla Volta G, Strada L, Gasparotti R, DiMonda V. Short-lasting unilateral neuralgiform headache attacks with tearing and conjunctival injection: the first "symptomatic" case? Cephalalgia 1991;11:123-127.

[13] 13. De Benedittis G. SUNCT syndrome associated with cavernous angioma of the brain stem. Cephalalgia 1996;16:503-506.

[14] 14. Morales F, Mostacero E, Marta J, Sanchez S. Vascular malformation of the cerebellopontine angle associated with "SUNCT" syndrome. Cephalalgia 1994;14:301-302.

[15] 15. Massiou H, Launay JM, Levy C, El Amrani M, Emperauger B, Bousser MG. SUNCT syndrome in two patients with prolactinomas and bromocriptine-induced attacks. Neurology 2001;58:1698-1699.

[16] 16. Piovesan EJ, Kowacs PA, Werneck LC. SUNCT syndrome: report of a case preceded by ocular trauma. Arq Neuropsiquiatr 1996;54:494-497.

[17] 17. Kruszewski P. Shortlasting, unilateral, neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome): V. Orbital phlebography. Cephalalgia 1992;12:387-389.

[18] 18. Sjaastad O, Kruszewski P, Fostad K, Elsas T, Ovigstad G. SUNCT syndrome: VII. Ocular and related variables. Headache 1992;32:489-495.

[19] 19. Zhao JM, Sjaastad O. SUNCT syndrome: VIII. Pupillary reaction and corneal sensitivity. Func Neurol 1993;8:409-414.

[20] 20. Shen JM, Johnsen HJ. SUNCT syndrome: estimation of cerebral blood flow velocity with transcranial Doppler ultrasonography. Headache 1994;34:25-31.

[21] 21. Poughias L, Aasly J. SUNCT syndrome: cerebral SPECT images during attacks. Headache 1995;35:143-145.

[22] 22. May A, Bahra A, Buchel C, Turner R, Goadsby PJ. Functional magnetic resonance imaging in spontaneous attacks of SUNCT: short-lasting neuralgiform headache with conjunctival injection and tearing. Ann Neurol 1999;46:791-794.

[23] 23. Graff-Radford SB. SUNCT syndrome responsive to gabapentin (neurotin). Cephalalgia 2000;20:515-517.

[24] 24. Porta-Etessam J, Benito-Leon J, Martinez-Salio A, Berbel A. Gabapentin in the treatment of SUNCT syndrome. Headache 2002;42:523-524.

[25] 25. Hunt CH, Dodick DW, Bosch EP. SUNCT responsive to gabapentin. Headache 2002;42:525-526.

[26] 26. Matharu MS, Boes CJ, Goadsby PJ. SUNCT syndrome: prolonged attacks, refractoriness and response to topiramate. Neurology 2002;58:1307.

[27] 27. Pareja JA, Caminero AB, Sjaastad O. SUNCT syndrome: diagnosis and treatment. CNS Drugs 2002;16:373-383.

[28] 28. Black DF, Dodick DW. Two cases of medically and surgically intractable SUNCT: a reason for caution and an argument for a central mechanism. Cephalalgia 2002;22:201-204.

[29] 29. Pareja JA, Kruszewski P, Sjaastad O. SUNCT syndrome: trial of drugs and anesthetic blockades. Headache 1995;35:138-142.

[30] 30. Zakrzewska JM, Chaudhry Z, Nurmikko TJ, Patton DW, Mullens EL. Lamotrigine (lamictal) in refractory trigeminal neuralgia: results from a double-blind placebo controlled crossover trial. Pain 1997;73:223-230.

[31] 31. Casey KL. Pain and central nervous system disease: the central pain syndromes. New York: Raven 1991.

[32] 32. Canavero S, Bonicalzi V. Lamotrigine control of central pain. Pain 1996;68:179-181.

[33] 33. D'Andrea G, Granella F, Cadaldini M. Possible usefulness of lamotrigine in the treatment of SUNCT syndrome. Neurology 1999;53:1609.

[34] 34. Leone M, Rigamonti A, Usai S, Damico D, Grazzi L, Bussone G. Two new SUNCT cases responsive to lamotrigine. Cephalalgia 2000;20:845-847.

[35] 35. D'Andrea G, Granella F, Ghiotto N, Nappi G. Lamotrigine in the treatment of SUNCT syndrome. Neurology 2001;72:866-871.

[36] 36. Tilignac C, Dordain G. SUNCT syndrome sensitive to lamotrigine. Presse Med 2001;30:1106.

[37] 37. Gutierrez-Garcia JM. SUNCT syndrome responsive to lamotrigine. Headache 2002;42:823-825.

[38] 38. Xie X, Lancaster B, Peakman T, Garthwaite J. Interaction of the antiepilelptic drug lamotrigine with recombinant rat brain type IIA Na⁺ channels and with native Na⁺ channels in rat hippocampal neurones. Pflugers Arch 1995;430:437-446.

[39] 39. Woolf CJ, Thompson SWN. The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation: implications for the treatment of post-injury pain hypersensitivity states. Pain 1991;44:293-299.

[40] 40. Nakamura-Craig M, Follenfant RL. Lamotrigine and analgesia: a new treatment for chronic pain? In Gebhart GF, Hammond DL, Jensen TS. (eds) Progress in pain research and treatment, vol 2 Seattle: IASP Press, 1994:725-730.

[41] 41. Nakamura-Craig M, Follenfant RL. Effect of lamotrigine in the acute and chronic hyperalgesia induced by PGE₂ and in the chronic hyperalgesia in rats with streptozocin-induced diabetes. Pain 1995;63:33-37.

[42] 42. Sterker M, Berrouschot J, Schneider D. Fatal course of toxic epidermal necrolysis under treatment with lamotrigine. Int J Clin Pharmacol Ther 1995;33:595-597.

[43] 43. Lunardi G, Leandri M, Albano C, et al. Clinical effectiveness of lamotrigine and plasma levels in essential and symptomatic trigeminal neuralgia. Neurology 1997;48:1714-1717.