doi:10.1111/j.1468-2982.2009.01956.x
CLINICAL CORRESPONDENCE
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Trigeminal neuralgia and trigeminal-autonomic cephalalgias: a continuum or simple co-existence? F Maggioni1, R Manara2, E Mampreso1, F Viaro1, F Mainardi3 & G Zanchin1 1
Headache Centre, Department of Neurosciences and 2Department of Neuroradiology, University of Padua, Padua, and 3Headache Centre,
Department of Neurosciences, Hospital SS. Giovanni e Paolo, Venice, Italy
Dr Ferdinando Maggioni, Headache Centre, Department of Neurosciences, University of Padua, 35128, Padua, Italy. E-mail
[email protected] Received 14 May 2009, accepted 16 June 2009
Trigeminal neuralgia (TN) is a common unilateral disorder characterized by brief electric shock-like pains, abrupt in onset and termination, limited to the distribution of one or more divisions of the trigeminal nerve. Indeed, pain is commonly evoked by trivial stimuli, including washing, shaving, smoking, talking, or brushing the teeth and frequently occurs spontaneously (1). Cluster headache (CH), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms, and paroxysmal hemicrania (PH) are classified as trigeminal-autonomic cephalalgias (TACs). These cephalalgias, according to International Classification of Headache Disorders, 2nd edn (ICHDII) criteria, share the clinical features of headache accompanied by cranial parasympathetic autonomic features (1). These syndromes seem to be different and well-characterized. However, in recent years some cases have been described in which syndromes co-existed or switched from one type to another in the same patient. This event raised doubt that there could be some common mechanisms among them. We describe a patient who resurrects this problem. She first presented with TN, later developed SUNCT, and then manifested TN attacks, followed by CH, and finally SUNCT without TN attacks.
Case report A 43-year-old secretary had a 3-year history of recurrent, sporadic attacks of stabbing pains, abrupt in onset and termination, localized in the first and second divisions of the right trigeminal nerve. On two occasions, the attacks had lasted about 3 weeks, so that she was treated successfully, first with © Blackwell Publishing Ltd Cephalalgia, 2009
carbamazepine (discontinued due to leucopoenia) and then with gabapentin (1600 mg). The patient came to our attention for the onset of a new paroxysmal pain. About 1 month before admission to our hospital, she presented with two kinds of attacks. The first type of attack involved a severe, stabbing pain that lasted a few seconds and was localized to the first and second branches of the right trigeminal nerve without autonomic features. There was wide variability in frequency, from two to 30 attacks a day, resembling those presented in the past. She also referred to the onset of a new type of short-lasting (from seconds to 4–5 min) stabbing pain, localized to the upper row of teeth, the nose, and orbital-temporal region, constantly on the right side, and associated with ipsilateral conjunctival injection, tearing, redness of the ipsilateral face, and with a mean of > 20 attacks daily. Both attacks were triggered by touching the face, talking, chewing and opening or closing both eyes, but only the first had a refractory period. Upon admission to our Headache Centre, the general and neurological examinations were normal. The complete blood count, ECG, chest X-rays and brain magnetic resonance imaging (MRI) with contrast were normal. An angio-MRI showed the presence of an arterial structure compressing the right trigeminal root in the nerve entry zone (Fig. 1). The patient declined surgical management. We obtained complete resolution of both attacks in approximately 1 month, with a combination of gabapentin (2400 mg/day) and amitriptyline (75 mg/day). About 8 months later, the patient had a relapse of pain attacks, but with different features. The pain attacks were spontaneous (not triggered), stabbing, severe, lasting from 20 min to 1–2 h, with a mean of two to three attacks daily, localized in the right orbital or supraorbital region, and associated in 1
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Figure 1 MRI showing right neurovascular conflict. (a) Axial T2 image with a high echo train length (ETL = 170) showing a thin linear antero-posterior structure (white arrowhead) close to the nerve entry zone of the right trigeminal nerve; the left trigeminal nerve is also recognizable (white arrow); in this high resolution sequence both nerves and vessels are hypointense. (b) Axial T1 gradient echo image post contrast medium intravenous administration at the same level showing the same structures as Fig. 1 (a); in this sequence the vessels appear hyperintense while the nerves are isointense, therefore the linear structure is a vessel. (c) Axial time of flight image of the intracranial arteries at the same level of fig a and b; the linear structure appears still hyperintense thus proving to be a segment of the right superior cerebellar artery (white arrowhead). MRI, magnetic resonance imaging.
various combinations with ipsilateral autonomic symptoms (conjunctival injection, tearing, redness of ipsilateral face and ptosis), and restlessness or agitation. We started methylprednisolone (80 mg/ day for 7 days) and verapamil (240 mg/day) with a progressive improvement of attacks, which disappeared completely in about 2 weeks. During this cluster, the attacks were responsive to subcutaneous injection of 6 mg of sumatriptan. Verapamil was discontinued 1 month after the last attack and amitriptyline was reduced to 25 mg/day; gabapentin was maintained at the previous dosage (2400 mg/day). After 6 months without attacks, despite the above-mentioned therapy, the patient presented with a relapse of pains, which had the same characteristics as the attacks presented on admission. The pains were stabbing, severe and localized in the right orbital or supraorbital regions, lasting from 3–4 s to 2–4 min, with a mean of 20 attacks per day, and always associated with ipsilateral conjunctival injection and tearing. On this occasion, the patient discontinued the gabapentin and was treated with lamotrigine (50 mg b.i.d.) with resolution of the attacks after about 1 month. Follow-up after 2 years was negative for reappearance of the attacks, and in the remission periods the patient was completely pain free. Therefore, she is still treated with lamotrigine (50 mg b.i.d.) because on two different occasions decreasing the dose had resulted in a recurrence of the attacks. The chronological features of the patient’s attacks are summarized in Table 1.
Discussion This case raises some points of interest and discussion. The possibility exists of evolution from TN to various forms of TAC, not only to the types with brief attacks, but even to the types with long-lasting crises, such as CH. Alternatively, the possibility exists of simple co-existence of the various kinds of syndromes in the same patient. Lastly, the importance of peripheral causes in the pathogenesis of TACs is suggested. Regarding the first point, some studies have focused on the association between TN and TACs with short-lasting attacks, such as SUNCT (2–5), or with medium-lasting attacks (> 20 min) such as PH (6, 7), with long-lasting attacks (> 180 min) such as CH (8, 9) and, finally, on the association with different kind of TACs in the same patient, e.g. SUNCT and CH (10). Most of the described SUNCT cases already originated as such, therefore SUNCT is currently classified as a TAC. However, the co-existence of SUNCT and trigeminal neuralgia in a single patient suggests a possible pathophysiological relationship. Moreover, Bouhassira et al. (4) and Sessa (5) have described SUNCT cases derived from TN. The case described here began as TN, later evolving to SUNCT. Nevertheless, during this SUNCT phase, severe painful crises with autonomic features were observed to alternate with minor crises accompanied by slight or no autonomic signs, suggesting that SUNCT is strongly related to TN, probably being a possible variant of the latter. Other © Blackwell Publishing Ltd Cephalalgia, 2009
© Blackwell Publishing Ltd Cephalalgia, 2009
TN
SUNCT
CH
Touching the face, talking, chewing and opening or closing both eyes
-
tried tried tried
tried
SUNCT
Not Not Not Not + 2
Mean of 20 attacks day
Severe + + -
Stabbing pain
Severe + + + + + + + +
Stabbing pain
From 3–4 s to 2–4 min Orbital or supraorbital (right side)
4th period
TN, trigeminal neuralgia; SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; CH, cluster headache; IHS, International Headache Society.
TN
tried
tried
tried tried tried tried tried
tried tried tried tried
Not tried + + + + Not tried Not tried + + 1
Not Not Not Not + + 1
Not Not Not Not Not Not + + 1
Not Not Not Not Not + Not + Not 36
tried
20/day
+ 10–15/day
Refractory period Number of attacks/day Response to: Indomethacin Sumatriptan Oxygen Methylprednisolone Verapamil Carbamazepine Lamotrigine Gabapentin Amitriptyline Illness duration (months) Diagnosis IHS tried tried tried tried tried
2–3/day
Touching the face, talking, chewing and opening or closing both eyes
Touching the face, talking, chewing and opening or closing both eyes
Touching the face, talking, chewing and opening or closing both eyes + 8–15/day
Intensity of pain Lacrimation Conjunctival injection Miosis and/or ptosis Nasal congestion Rhinorrhoea Eyelid oedema Facial sweating Restlessness or agitation Triggers
Quality of pain
From 30 min to 1–2 h Orbital or supraorbital region (right side)
Severe + + -
From seconds to 4–5 min Upper row of teeth, nose, orbital or supraorbital region (right side) Stabbing pain
Seconds First and second branch of trigeminal nerve (right side) Brief electric shock-like pain Severe -
Seconds First and second branch of trigeminal nerve (right side) Brief electric shock-like pain Severe -
3rd period
Duration of pain Location and side of pain
2nd period
1st period
Clinical features
Table 1 Features of the patient’s attacks in the different periods of the illness
Trigeminal neuralgia and TACs 3
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reports propose the association of TN and TACs: PH-tic syndrome (7, 8) and CH-tic syndrome (9). Only one case has been reported in which there is an association between TN and TACs with short- and long-lasting attacks (10). Furthermore, in this case the crises were associated randomly with each other (10). In our case, we noted evidence of four different and clearly distinct clinical phases. In the first phase, before admission to our centre, the patient presented with isolated TN attacks with a variable frequency (approximately 3 years), responding first to carbamazepine (discontinued due to leucopoenia), and then to gabapentin. In the second phase, she had co-existence of TN attacks and of a syndrome that with respect to pain localization, quality, temporal pattern, and accompanying symptoms is typical for SUNCT (1). The therapy led to a remittance of the attacks with a combination of amitriptyline and gabapentin; the acute attacks were non-responsive to triptans or non-steroidal anti-inflammatory drugs, and even O2 therapy was administered without improvement. Eight months after the first remittance of pain attacks, the patient came again to our attention with attacks of pain and a pattern typical of CH, both in terms of length of the pain and the accompanying symptoms (in this case, restlessness). Furthermore, these attacks lasting > 15 min were responsive to a subcutaneous injection of sumatriptan (6 mg), and partially to O2 therapy. Also, shortterm prophylaxis therapy with steroids and longterm therapy with verapamil contributed to an improvement and then to remittance of the attacks. In the third phase, which developed about 8 months later, the patient complained of recurrence of the attacks similar to those which existed at the time of the first admission to our centre (stabbing, short, frequent, strictly associated with ipsilateral conjunctival injection and tearing suggestive of SUNCT, but not accompanied with TN attacks). We emphasize that after the second phase, the patient did not present with further attacks with TN features, whereas, as reported by Alberca and Ochoa (9), CH-tic syndrome is pathognomonic in the presence of mixed attacks (9). It is difficult to explain which causes could modify one syndrome into another (environmental factors or different phenotypes of a single pathology, or different syndromes casually linked in the same patient). The syndromes are, in fact, clinically well-characterized and, with the exception of the second phase, presented not linked to one another, and even the treatments are specific, as summarized in Table 1. On the other hand, it is unusual for relatively rare syndromes to be associated by chance in the same patient.
Regarding the importance of central causes in the pathogenesis of TACs, many studies have demonstrated the pivotal role of hypothalamic involvement in CH headaches and some evidence in other TACs (11–14). There are, therefore, forms of TACs that are clearly derived from peripheral lesions, not only secondary to neurovascular conflicts, but to other causes, the removal of which leads to resolution (15–17). In our case, an important point to distinguish the different syndromes could be represented by the peripheral stimulation of the trigeminal nerve by neurovascular conflict located on the same side of the attacks. It is reported that neurovascular conflicts are present not only in TN, but also in TACs (18), and microvascular decompression of the trigeminal nerve may be useful in TN and in TACs: CH (19) and SUNCT (20, 21). Our patient satisfied the neuroradiological criteria for neurovascular conflict according to Burges and Castelman (22), as follows: (i) the offending vessel must be an artery; (ii) the site of contact must be the root entry zone; (iii) the vessel must cross the nerve perpendicularly; and (iv) the nerve must be deviated or indented by the vessel or compressed or encased between two or more adjacent vessels in the appropriate clinical setting. In contrast, asymptomatic neurovascular conflicts are a relatively common finding and in the ICHD-II the presence of this condition is compatible with the diagnosis of classic TN (1). It is impossible to verify the importance of neurovascular conflict in this case as the patient declined a surgical approach. We can hypothesize that the neurovascular conflict, as a trigger factor, could be common for all the syndromes and activate different pathways with alternate presentations of the peculiar features as a unifying hypothesis. Indeed, considering that the conflict had no influence, we could view the patient as affected casually by three distinct forms of primary cephalalgias. The second point is difficult to explain because these syndromes maintain peculiar characteristics. In conclusion, we think that it is important to describe new cases in which we find an association of TN and TACs in order to clarify further the clinical features of these composite syndromes with the hope of improving our understanding of their pathogenesis.
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