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Review Article
SUNCT/SUNA and neurovascular compression: New cases and critical literature review
Cephalalgia 0(0) 1–12 ! International Headache Society 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0333102413494273 cep.sagepub.com
Valentina Favoni, Daniela Grimaldi, Giulia Pierangeli, Pietro Cortelli and Sabina Cevoli Abstract Background: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache with cranial autonomic symptoms (SUNA) are primary headache syndromes. A growing body of literature has focused on brain magnetic resonance imaging (MRI) evidence of neurovascular compression in these syndromes. Objective: The objective of this article is to assess whether SUNCT is a subset of SUNA or whether the two are separate syndromes and clarify the role of neurovascular compression. Method: We describe three new SUNCT cases with MRI findings of neurovascular compression and critically review published SUNCT/SUNA cases. Results: We identified 222 published SUNCT/SUNA cases. Our three patients with neurovascular compression added to the 34 cases previously described (16.9%). SUNCT and SUNA share the same clinical features and therapeutic options. At present, there is no available abortive treatment for attacks. Lamotrigine was effective in 64% of patients; topiramate and gabapentin in about one-third of cases. Of the 34 cases with neurovascular compression, seven responded to drug therapies, 16 patients underwent microvascular decompression of the trigeminal nerve (MVD) with effectiveness in 75%. Conclusions: We suggest that SUNCT and SUNA should be considered clinical phenotypes of the same syndrome. Brain MRI should always be performed with a dedicated view to exclude neurovascular compression. The high percentage of remission after MVD supports the pathogenetic role of neurovascular compression. Keywords SUNCT, SUNA, autonomic, neurovascular compression, microvascular decompression Date received: 25 February 2013; revised: 13 May 2013; 20 May 2013; accepted: 21 May 2013
Introduction Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a primary headache syndrome characterized by unilateral stabbing or throbbing orbital or temporal pain. There should be at least 20 attacks, lasting 5–240 seconds, and both ipsilateral conjunctival injection and lacrimation (1). Only one of those symptoms or other cranial autonomic signs, along with a longer duration of attacks (two seconds–10 minutes), characterize short-lasting unilateral neuralgiform headache with cranial autonomic symptoms (SUNA), which is currently classified in the Appendix of the International Classification of Headache Disorders, 2nd edition (ICHD-II) (1). It is not clear whether SUNCT is a subset of SUNA or whether the two are separate entities (1–3). In addition,
the growing magnetic resonance imaging (MRI) evidence of neurovascular compression in SUNCT/ SUNA cases, commonly detected in the classic trigeminal neuralgia, raises the question of whether it is an incidental finding or a symptomatic cause (2,3). We describe three new SUNCT cases with brain MRI finding of neurovascular compression and critically review
IRCCS Institute of Neurological Sciences of Bologna, Headache Centre, Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy Corresponding author: Sabina Cevoli, IRCCS Institute of Neurological Sciences of Bologna, Ospedale Bellaria, Via Altura, 3, 40139 Bologna, Italy. Email:
[email protected]
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2 published literature on SUNCT/SUNA cases, including therapeutic options.
Methods We describe three new SUNCT patients with brain MRI finding of neurovascular compression attending our headache center between February 2009 and November 2011. We electronically searched PubMed using the following keywords: trigeminal, autonomic, neuralgia, SUNCT, SUNA, lacrimation, tearing, rhinorrhea, nasal congestion, ptosis, miosis, mydriasis, eyelid edema, facial flushing, sweating, neurovascular compression and microvascular decompression (MVD). We screened the English-language literature to identify SUNCT and SUNA cases, including those with neurovascular compression. We carefully reviewed the reference lists of all the papers found. A few abstracts were included. Secondary SUNCT/SUNA cases were excluded to have a homogeneous group for comparison. However, we were not able to exclude three secondary cases reported in the largest SUNCT/ SUNA series (one SUNA patient with multiple sclerosis and two SUNCT patients with pituitary lesions) because they were not reported separately. Only cases with both conjunctival injection and tearing were classified as SUNCT, according to ICHD-II criteria. We focused on the following clinical items: trigeminal involvement and neurovascular compression, gender, age at onset, laterality of pain, cranial autonomic symptoms, triggers, refractory period, therapeutic options and surgical treatment. Statistical analysis was performed using chi square for categorical data, and unpaired two-tailed t test for continuous variables. A p value < 0.05 was considered significant.
Results Case 1 (4) A 55-year-old man with familial thrombocytopenia complained of headache attacks since the age of 46 years. The headache was characterized by severe shock-like burning pain occurring over the right orbital and temporal areas, accompanied by ipsilateral conjunctival injection, ptosis, lacrimation and rhinorrhea. The attacks occurred spontaneously or could be triggered by shaving, chewing or touching the right side of the face. A refractory period after tactile allodynic elicitations was absent. During the attacks the patient was restless and irritable. At onset, he had clusters of attacks with stabs lasting 30–60 seconds that would occur for several minutes (up to 40 minutes), from one to six times a day, mainly during daytime, for nearly a month once a year. Physical and neurological
Cephalalgia 0(0) examinations were normal. He was administered gabapentin (600 mg daily) and was rendered asymptomatic. In the last year before our examination the attacks had worsened in frequency, occurring daily and nightly about 15 per hour becoming shorter in duration (seconds). Therapy with pregabalin 300 mg/day and verapamil 240 mg/day proved ineffective. Intravenous corticosteroids (methylprednisolone 500 mg/day) were then administered for three days without efficacy, thus they were discontinued together with the other preventive agents, and indomethacin up to 150 mg/day and carbamazepine (CBZ) up to 1000 mg/day were started. After two days the attacks had dramatically decreased in frequency. Indomethacin was stopped after one month when a complete remission was achieved and maintained with CBZ only. Repeated attempts to stop CBZ led to a recurrence of attacks. A brain MRI performed at the onset of symptoms was interpreted as normal. A second MRI was repeated after the worsening of headache and documented an aberrant loop of the right superior cerebellar artery compressing the ipsilateral trigeminal nerve (Figure 1). The good response to pharmacological treatment and the presence of thrombocytopenia contraindicated surgical MVD.
Case 2 A 53-year-old woman with a medical history of hypertension and glaucoma presented with a three-year history of headache. She described strictly right-sided episodes of severe electric shock-like pain, occurring on periorbital and temporal areas, accompanied by prominent ipsilateral lacrimation, conjunctival injection, rhinorrhea, miosis and facial flushing. The attacks occurred spontaneously or could be triggered by touching the face, talking, chewing and moving the eyes. The pain usually lasted from two seconds to three minutes, occurring daily and nightly more than 100 times daily, for nearly a month once a year. Brain MRI performed at the onset of symptoms demonstrated hypo-density of the left caudate nucleus, compatible with a lacunar area. Therapy with oxygen, opioid analgesics, anticonvulsants (lamotrigine and valproic acid), and nonsteroidal analgesics, including indomethacin, proved ineffective. The patient came to our attention in February 2011 because of worsening headache. Neurologic examination displayed anisocoria, allodynia and hyperesthesia over the right trigeminal distributions during the attacks. The right corneal reflex could trigger the attacks. A refractory period was absent. A diagnosis of SUNCT was made. A second MRI scan documented right superior cerebellar artery compression on the ipsilateral trigeminal nerve (Figure 2). The patient was administered CBZ
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Figure 1. FSPGR MPR coronal reconstructed image (a) revealed the trigeminal nerve in its cisternal tract, bilaterally (arrows); 3DTOF MR angiography sequence MPR coronal reconstruction (b) showed the contact between left superior cerebellar artery and the upper surface of the nerve (arrowhead). FSPGR: fast spoiled gradient echo; MPR: multi-planar reconstruction; 3D-TOF MR: three-dimensional time-of-flight magnetic resonance.
Figure 2. FISP MPR coronal reconstructed image (a) revealed the trigeminal nerve in its cisternal tract, bilaterally (arrows); 3D-TOF MR angiography sequence MPR coronal reconstruction (b) and MIP reconstruction (c) showed the contact between right superior cerebellar artery and the upper surface of the nerve (arrowhead). FISP: fast imaging with steady-state precession; MPR: multi-planar reconstruction; 3D-TOF MR: three-dimensional time-of-flight magnetic resonance; MIP: maximum intensity projection.
(600 mg/day), pregabalin (450 mg/day) and indomethacin (150 mg/day) that maintained her asymptomatic for three months. Following a head trauma in September 2011 the symptoms recurred. The patient was again administered CBZ (600 mg/day), pregabalin (450 mg/day) and indomethacin (150 mg/day) with partial improvement. In March 2012, she finally underwent MVD of the trigeminal nerve, which determined a complete disappearance of symptoms during the following 11 months of observation, without any prophylactic therapy.
Case 3 A 47-year-old man with an unremarkable medical history complained of headache attacks since the age of 44
years. At onset, the attacks were characterized by severe shock-like pain occurring on the right orbital area, ear and nose, accompanied by ipsilateral conjunctival injection, ptosis and lacrimation. Usually the headache lasted from 30 to 60 seconds and occurred > 20 times a day. The patient was pain free at nighttime unless he got up. The attacks occurred spontaneously or could be triggered by moving the head, washing or touching the right side of the face, chewing, or wind hitting the face. Initially, the patient was misdiagnosed as having right chronic sinusitis on the basis of sinus computed tomography (CT) scan evidence. Sinusotomy using balloon catheter devices was attempted but after surgery he experienced worsening headache. Brain MRI documented a neurovascular compression. The patient underwent first gamma
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4 knife treatment without any improvement and one year later surgery for MVD. During the procedure, the compression of the right superior cerebellar artery and right peritrigeminal vein on the ipsilateral trigeminal nerve was identified and a Teflon sponge was interposed to maintain the separation. After four weeks the attacks returned with the same features previously described, but the patient was now experiencing a continuous burning pain involving all three branches of the right trigeminal nerve. A trial with CBZ (up to 600 mg daily) offered little benefit and was poorly tolerated. Gamma knife and sinusotomy were performed again without any improvement. Therefore, in November 2011, the patient came to our attention and the neurological examination showed only dysesthesia within the right V1-V2-V3 trigeminal areas. Repeat brain MRI with gadolinium documented greater thickness and contrast enhancement of the right trigeminal nerve, compatible with inflammation. The cerebrospinal fluid demonstrated a normal opening pressure (200 mmH20) and no oligoclonal bands, excluding central nervous system (CNS) inflammation. Intravenous corticosteroids were started without lasting benefit. Treatment with indomethacin (150 mg daily) was ineffective. Lamotrigine (up to 450 mg daily), amitriptyline (50 mg daily) and palmitoylethanolamide (600 mg daily) seemed to reduce the lacrimation, but not the frequency or intensity of attacks. Verapamil (240 mg daily) was added without improvement. Oxcarbamazepine (1200 mg daily) plus lamotrigine provided benefit proximally by 50% on both anesthesia dolorosa and SUNCT attacks.
Cephalalgia 0(0) views for the trigeminal nerve (3). By contrast, a vascular compression of the trigeminal nerve was seen in only three SUNCT patients (7%) in the largest series of 52 SUNCT/SUNA cases (2). The vessels in contact with the trigeminal nerve were the superior cerebellar artery (SCA) alone in 17 cases (50%) (3,5,15– 17,19,20,22,23,25–27), the anterior inferior cerebellar artery (AICA) alone in one patient (3%) (17), and the vertebral artery in one patient (3%) (21). Both SCA or AICA and vein were involved in three cases (9%) (3,5). Bilateral loop was reported in five cases (14.7%) (2,3,5). Results from the literature review on neurovascular compression are presented in Table 1.
Gender and age at onset Considering all patients together, information on sex and age at onset were available in 215 (96.8%) and 200 (90.1%) cases, respectively. A total of 109 SUNCT patients were male and 74 female (M:F ratio of 1.5 : 1). Eleven SUNA cases were male and 19 female (M:F ratio of 1 : 1.7). The two cases with both SUNCT and SUNA attacks were male patients, aged 54 and 58 years, respectively (3,5). The mean age at onset was 47.62 17.11 years considering all patients together: 48.30 17.33 years in SUNCT patients and 42.29 15.64 years in SUNA syndrome, with no significant difference (p ¼ 0.131). Among SUNCT/SUNA patients with MRI evidence of neurovascular compression, 19 were male and 12 female (M:F ratio of 1.6 : 1). Age ranges at onset were available in 31 cases. The mean age at onset was 49.19 14.01 years.
Literature review We found 222 cases in the literature. Of these, 189 had SUNCT attacks, 31 SUNA (2,3,5–15), two both SUNCT and SUNA (3,5).
Trigeminal involvement and neurovascular compression A total of 201 of 222 (90.5%) published cases of SUNCT/ SUNA reviewed were investigated by brain MRI. Thirty-four of 201 cases (16.9%) had MRI evidence of vascular compression of the trigeminal nerve (2,3,5,7,15–27). Twenty-seven were SUNCT patients, five were SUNA (3,5,7,15) and two had both SUNCT and SUNA attacks (3,5). Unfortunately, many reports do not clarify whether MRI-dedicated views of the trigeminal nerve root were performed, so the presence of neurovascular compression may be underestimated. In particular, in a series of 24 SUNCT/SUNA cases, neurovascular compression was detected in 15 of 17 patients (88%) who underwent MRI with dedicated
Cranial autonomic symptoms Autonomic features were described in 158 (83.6%) of 189 SUNCT patients and in 26 (83.9%) of 31 SUNA. Comparing SUNCT and SUNA patients, statistically significant differences were observed only for conjunctival injection and lacrimation: 158 vs seven (100% vs 26.9%, p < 0.001) and 158 vs 12 (100% vs 46.2%, p < 0.001), respectively. Autonomic symptoms were clearly described in 17 (50%) of 34 SUNCT/SUNA patients with MRI evidence of a neurovascular compression. No statistically significant differences were observed comparing patients with and without neurovascular compression. The distribution of cranial autonomic symptoms is shown in Table 2.
Laterality of pain The side of attacks was available in 205 (92.3 %) of 222 patients. Ninety-two (44.8%) had left-sided attacks, 90 (43.9%) right-sided attacks, seven (3.4%) unilateral
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Favoni et al. attacks, but the side was not available; 12 (5.9%) patients had side-shift attacks, four (2%) bilateral attacks. Among SUNCT/SUNA patients with MRI evidence of a neurovascular compression, 13 (38.2%) patients had left-sided attacks, 15 (44.1%) had right-sided attacks, two (5.9%) had unilateral attacks, but the side was not available; one patient (2.9%) had sideshift attacks and three (8.8%) had bilateral attacks (Table 1).
Triggers Data on triggers factors were reported in 176 (79.3%) of 222 patients. Triggers such as touching the face, washing, shaving, eating, chewing, brushing teeth, talking, coughing or neck movement were identified in 128 (72.7%) of 176 patients. Conversely, 48 (27.3%) patients had exclusively spontaneous attacks. Of the 34 SUNCT/SUNA patients with neurovascular compression, 26 (76.5%) had triggers, five (14.7%) had
Table 1. Neurovascular compression in SUNCT and SUNA patients. Authors
Age at onset
Sex
Diagnosis
Pain side
Trigger factors
Refractory period
Neurovascular compression
Effective treatment
Ertsey et al. 2000 (16)
68
M
SUNCT
R
Yes
N/A
SCA
CBZ þ tiapride
Gardella et al. 2001 (17) Ko¨seoglu et al. 2005 (18)
43
F
SUNCT
R
Yes
N/A
SCA
MVD
48
M
SUNCT
L
Yes
N/A
AICA
None
Lagares et al. 2005 (19)
54
F
SUNCT
L
Yes
No
SCA
MVD
Sprenger et al. 2005 (20)
47
M
SUNCT
R
Yes
N/A
SCA
MVD
Zidverc-Trajkovic et al. 2005 (21)
68
M
SUNCT
L
Yes
N/A
VA
GBP
Cohen et al. 2006 (2)
N/A
N/A
SUNCT
U
N/A
N/A
VL
N/A
Cohen et al. 2006 (2) Cohen et al. 2006 (2)
N/A N/A
N/A N/A
SUNCT SUNCT
U Bilateral
N/A N/A
N/A N/A
Bilateral VL VL
N/A N/A
Williams et al. 2008–2010 (3,5)
43
F
SUNCT
Bilateral
Yes
No
Bilateral SCA
None
Williams et al. 2008–2010 (3,5)
53
M
SUNCT
L
No
No
AICA and V
MVD
Williams et al. 2008–2010 (3,5)
46
F
SUNCT
R
Yes
No
SCA
MVD
Williams and Broadley 2008 (3)
47
F
SUNCT
L/R
Yes
No
Bilateral A
N/A
Williams and Broadley 2008 (3)
17
F
SUNCT
Bilateral
Yes
No
Bilateral A
N/A
Williams et al. 2008–2010 (3,5)
46
F
SUNA
L
Yes
No
AICA and V
None
Williams and Broadley 2008 (3) Williams et al. 2008–2010 (3,5)
19 58
F M
SUNCT SUNCT/SUNA
L R
No No
No No
A SCA and V
N/A None
Williams et al. 2008–2010 (3,5)
19
M
SUNCT
L
Yes
No
SCA
MVD
Williams et al. 2008–2010 (3,5)
55
M
SUNA
R
Yes
No
SCA
MVD
Williams et al. 2008–2010 (3,5)
65
F
SUNCT
R
Yes
No
SCA
MVD
Williams and Broadley 2008 (3)
58
M
SUNA
L
No
No
A
N/A
Williams and Broadley 2008 (3)
32
F
SUNCT
R
Yes
No
Bilateral A
N/A
Williams et al. 2008–2010 (3,5)
54
M
SUNCT/SUNA
L
Yes
No
SCA
MVD
Williams and Broadley 2008 (3) Jacob et al. 2008 (7)
54 29
M M
SUNCT SUNA
L R
Yes No
No No
A VL
N/A GBP
Guerreiro et al. 2009 (22)
57
M
SUNCT
L
Yes
N/A
SCA
MVD
Irimia et al. 2010 (23)
54
M
SUNCT
L
Yes
No
SCA
MVD
Maggioni et al. 2010 (24)
40
F
SUNCT
R
Yes
No
A
LMT; GBP þ amitryptiline
Bartsch et al. 2011 (25)
67
M
SUNCT
R
Yes
N/A
SCA
DBS
Chaila et al. 2011 (26)
45
M
SUNCT
L
Yes
N/A
SCA
MVD
Paliwal et al. 2012 (27)
60
M
SUNCT
R
Yes
Yes
VL
OXA þ LMT
Paliwal et al. 2012 (27) Paliwal et al. 2012 (27)
55 64
M M
SUNCT SUNCT
R R
Yes Yes
Yes Yes
SCA SCA
LMT CBZ
Rinaldi et al. 2013 (15)
60
F
SUNA
R
Yes
N/A
SCA
None
SUNCT: short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; SUNA: short-lasting unilateral neuralgiform headache with cranial autonomic symptoms; M: male; F: female; L: left; R: right; U: unilateral; AICA: anterior inferior cerebellar artery; SCA: superior cerebellar artery; VA: vertebral artery; VL: vascular loop; A: artery; V: vein; CBZ: carbamazepine; MVD: microvascular decompression; LMT: lamotrigine; GBP: gabapentin; DBS: deep brain stimulation; OXA: oxacarbazepine; N/A: not applicable.
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only spontaneous attacks and in three cases data were not available (2).
Refractory period Data on a refractory period were available in 93 (41.9%) of 222 SUNCT/SUNA cases. No refractory period was reported in 84 (90.3%) cases. Nine (9.7%) patients had a preserved refractory period (2,27–30). Three of them had MRI evidence of neurovascular compression (27).
SUNCT/SUNA: Therapeutic options Lamotrigine alone (up to 400 mg) was effective in 52 of 81 patients (64.2%) (3,10,12,27,31–42), gabapentine (up to 3600 mg) in 24 of 71 (33.8%) (7,31,43–47), topiramate (up to 400 mg) in 14 of 43 (32.6%) (32,48,49), CBZ (200–1200 mg) in 25 of 119 (21%) (3,7,12,27,31,50–53), oxcamazepine in one of seven (14.3%) (54), corticosteroids in seven of 22 (31.8%) (30,40,46,55,56), verapamil in one of 18 (5.5%) (57), zonisamide in one of two (58), and lomerazide hydrochloride in one of two patients (9). Indomethacine was effective in only one out of 129 cases (0.78%) (59). Other anti-inflammatory drugs were completely ineffective. None of the 28 patients who received triptans achieved benefits. Headache remission was achieved in 22 of 26 (84.6%) patients treated with intravenous lidocaine and in nine of 11 (81.8%) patients who tried subcutaneous lidocaine
(3,5,10,31,60). A complete response to associations of two or more drug therapies was reported in single cases (Table 3). Of the 34 SUNCT/SUNA patients with MRI evidence of a neurovascular compression, pharmacological treatment was reported as effective in seven cases and ineffective in 16 patients (Table 1).
Surgical treatment MVD. Sixteen of 34 (47.1%) patients with MRI findings of a neurovascular compression underwent MVD of the trigeminal nerve. Twelve were SUNCT patients, two SUNA and two had both SUNCT and SUNA attacks (5,17,19,20,22,23,26). Complete pain relief was achieved in 12 of the 16 patients (75%) lasting up to 32 months after surgery. In addition, three more SUNCT patients with normal MRI studies were unsuccessfully treated with MVD (61,62). Two of them had been previously treated with a trigeminal ablative procedure (61). Data about MRI findings preceding MVD were not available in two SUNCT patients. One of them was asymptomatic for two years following surgery, then the pain recurred (52). The second one experienced a complete resolution of symptoms after three months of follow-up (63) (Table 1). Local blockades. Blockade of the greater occipital nerve (GON) was performed in 25 patients. Seven SUNCT patients (28%) achieved a good response: five cases with lidocaine and depomedrone (31), one with bupivacaine (64), and another one with an association of
Table 2. Autonomic features. SUNCT/SUNA with neurovascular compression
SUNCT/SUNA without neurovascular compression
SUNCT
SUNA
(pts ¼ 158)
(pts ¼ 26)
SUNCT vs SUNA
(pts ¼ 17)
(pts ¼ 167)
SUNCT/SUNA with vs without neurovascular compression
n (%)
n (%)
p
n (%)
n (%)
p 0.83
Conjunctival injection
158 (100%)
7 (26.9%)
