Background. Short-lasting unilateral neuralgiform headache attack with conjunctival injection and tearing (SUNCT) is one of the trigeminal autonomic cephalalgias where neurovascular compression was detected in neuroimaging in recent years.

Case. We report two cases, a 52-year-old adult and a 69-year-old elderly patient with short-lasting and recurrent headache combined with cranial autonomic features. Diffusion tensor imaging (DTI) and magnetic resonance (MR) tractography of both patients outlined structural changes of the trigeminal nerve revealing neurovascular compression. Pain and autonomic symptoms were completely relieved in the 52-year-old patient who underwent microvascular decompression surgery.

Conclusion. To our knowledge, this is the first time in the literature where MR tractography revealed structural changes in the trigeminal nerve secondary to neurovascular compression in SUNCT patients. We suggest that in SUNCT patients high-resolution magnetic resonance imaging (MRI) and/or DTI-MR tractography should be performed to exclude neurovascular compression. We propose that the compression of the trigeminal nerve could generate SUNCT symptoms and the posterior hypothalamus could be activated secondarily. With this point of view, trigeminal neuralgia and SUNCT could represent the different features of the neurovascular compression spectrum.

Introduction

Short-lasting unilateral neuralgiform headache attack with conjunctival injection and tearing (SUNCT) is one of the trigeminal autonomic cephalalgias (TACs), which is characterized by repetitive short-lasting and severe attacks. Headache attacks are in the distribution of the ophthalmic and maxillary divisions of the trigeminal nerve and are associated with ipsilateral autonomic phenomena [1]. SUNCT is a very rare condition, with an annual incidence of 1.2 per 100,000 [2]. The disorder is usually episodic and predominant in males, with a peak age around 50 years. The diagnostic criteria for SUNCT specifies that the pain attacks last between one and 600 seconds and that the attacks have a frequency of at least one a day for more than half of the time when the disorder is active [1]. The pathophysiology of SUNCT is unknown [1]. The activation of the posterior hypothalamus is demonstrated in functional neuroimaging studies during the attacks [3]. A growing body of literature has focused on brain magnetic resonance imaging (MRI) evidence of neurovascular compression in these syndromes. Neurovascular compression (NVC) is a common cause of trigeminal neuralgia. There are few case reports in the literature with vascular compression of the trigeminal nerve shown in SUNCT patients [4–8]. We describe two new SUNCT cases with high-resolution MRI and DTI-MR tractography delineating structural changes in the trigeminal nerve secondary to vascular compression. We report for the first time that neurovascular compression of the trigeminal nerve was demonstrated in DTI-MR tractography in SUNCT patients. Our findings suggest that the compression of the trigeminal nerve may be the underlying cause of SUNCT symptoms in our patients.

Methods

High-resolution MRI and DTI-MR tractography of two SUNCT cases diagnosed according to the International Classification of Headache Disorders-3 beta (ICHD-3 beta) were reviewed.

Magnetic Resonance Imaging Protocol

MR examinations were performed with a 3T MR unit (Verio; Siemens Medical Solutions, Erlangen, Germany) by using an eight-channel head-array coil and parallel imaging techniques. Before taking DTI, 3D T1 weighted images (T1 3D MPRAGE) were done with the following parameters; axial 1-mm thick sections (TR = 1,900 ms, TE = 2.52 ms, TI = 900 ms, fractional anisotropy [FA] = 9 degree, matrix =256x256, FOV = 250 mm2). DTI was acquired with a 30-direction, single-shot, spin-echo echo-planar sequence. Imaging parameters were as follows: TR = 3,600 ms; TE = 95 ms; field of view (FOV) = 23 cm2; section thickness = 4 mm, matrix = 128x128; b values = 0 and 1,000 s/mm2.

Analysis of diffusion-tensor imaging data was performed by using NEURO 3D on the commercially available workstation (Syngo MR B15 Siemens, Erlangen, Germany). After using an algorithm of motion correction and image distortion due to eddy currents, FA, apparent diffusion coefficient (ADC), and color-coded structural DTI maps were generated on a pixel-by-pixel basis. Each trigeminal nerve was manually segmented by a neuroradiologist from the b = 0 image on the section on which the cisternal segments were clearly seen. ADC and FA values were measured for each trigeminal nerve using a manually seeded region of interest (ROI) at the midpoint of cisternal part of the nerve. Tractography reconstruction of the trigeminal nerve was performed. Multiple seed points were used to depict the fibers of the trigeminal nerve. The mean value of DTI parameters at each trigeminal nerve was calculated and analyzed.

Case Reports

Case 1

A 52-year-old woman presented with a six-year history of severe right side pain. The pain was localized in the right periorbital and temporal area. The headache was characterized by severe excruciating pain, accompanied by prominent ipsilateral conjunctival injection and lacrimation. The attacks mostly occurred spontaneously but also were triggered by chewing or touching the right periorbital area. Pain duration was one to two minutes. She had numerous attacks throughout the day and she could not tell the exact number of attacks. The patient described a new attack occuring immediately after cessation of the previous one. She was diagnosed with SUNCT clinically [1]. She did not respond to indomethacin (225 mg/day), carbamazepine (1,600 mg/day), lamotrigine (200 mg/day), or pregabaline (600 mg/day). Supraorbital, infraorbital, and stellate ganglion blockade were also ineffective. She reported a period of remission lasting a month with sodium valproate treatment (2,000 mg/day). Her pain spread to the maxillary division of the trigeminal nerve two months after the onset.

Physical and neurological examinations were normal. Routine blood and urine analyses were unremarkable. MRI of the brain revealed no significant findings. We performed high-resolution MRI and DTI-MR tractography (Figure 1), which showed the neurovascular compression of the trigeminal nerve by the superior cerebellar artery, and the latter outlined structural changes in the trigeminal nerve by showing a decrease in the FA value. FA values for the trigeminal nerves were 0.25 ± 0.072 (mean ± SD) on the right side and 0.28 ± 0.056 (mean ± SD) on the left side. The affected side was lower than the nonaffected side. ADC values were 2.76 ± 0.16 mm2/sec (mean ± SD) on the right side and 2.76 ± 0.36 mm2/sec (mean ± SD) on the left side. There was no difference between the ADC values.

Figure 1

High-resolution magnetic resonance imaging (MRI) axial image shows the indentation of the cisternal segment of the trigeminal nerve by the superior cerebellar artery on the right (A). In MR tractography (B and C), the relationship between the vascular structure (arrow) and the trigeminal nerve is obvious, and fractional anisotropy value on the right side is lower than the left side (0.25 ± 0.072 on the right side and 0.28 ± 0.056 on the left side).

Figure 1

High-resolution magnetic resonance imaging (MRI) axial image shows the indentation of the cisternal segment of the trigeminal nerve by the superior cerebellar artery on the right (A). In MR tractography (B and C), the relationship between the vascular structure (arrow) and the trigeminal nerve is obvious, and fractional anisotropy value on the right side is lower than the left side (0.25 ± 0.072 on the right side and 0.28 ± 0.056 on the left side).

Neurovascular compression of the trigeminal nerve is shown in 90–95% of the classic trigeminal neuralgia patients [9], therefore the differential diagnosis of SUNCT and trigeminal neuralgia is important in the patients with neurovascular compression. First division involvement in trigeminal neuralgia is rare, and autonomic symptoms are not characteristic of trigeminal neuralgia but mild autonomic phenomena can be seen due to trigemino-parasympathetic reflex whereas autonomic features are predominant in SUNCT. In SUNCT, pain can be triggered similar to trigeminal neuralgia; however, SUNCT is usually triggered without a refractory period [1,8] between the attacks as in this case, in contrast to trigeminal neuralgia where there is a refractory period between the attacks [1]. As this patient had periorbital and temporal pain with marked ipsilateral conjunctival redness and lacrimation and no refractory period between the attacks, she was diagnosed with SUNCT clinically. The patient defined both conjunctival injection and tearing during the attacks; therefore, she was diagnosed as SUNCT but not SUNA [1].

She underwent microvascular decompression surgery; an anteriorly placed vascular loop of superior cerebellar artery was seen indenting the trigeminal nerve (Figure 2), and complete pain relief was achieved after the surgery.

Figure 2

Coronal (A) and sagittal (B) magnetic resonance (MR) tractography images show the close relationship (arrows) between the vascular structure (superior cerebellar artery in this case) and the trigeminal nerve. After the surgery, coronal and sagittal images from the same planes (C and D) show the implant material (arrowheads) and the trigeminal nerve is released from the vascular compression.

Figure 2

Coronal (A) and sagittal (B) magnetic resonance (MR) tractography images show the close relationship (arrows) between the vascular structure (superior cerebellar artery in this case) and the trigeminal nerve. After the surgery, coronal and sagittal images from the same planes (C and D) show the implant material (arrowheads) and the trigeminal nerve is released from the vascular compression.

Case 2

A 69-year-old woman presented with a five-month history of severe pain localized in the right periorbital area. The headache was characterized by severe stabbing pain, accompanied by significant ipsilateral conjunctival redness and tearing. She described a high number attacks, which generally occurred spontaneously but were also triggered by chewing and touching the right periorbital area. Pain duration was two to three minutes. She had no refractory period between the attacks. She was diagnosed with SUNCT, and lamotrigine was tried but showed no effects on headache frequency. Later carbamazepine was started (400 mg/day), and we performed supraorbital and infraorbital nerve blockade, which were effective. She reported a period of remission for fifteen days. Fifteen days later, her pain attacks began again and we increased the dosage of carbamazepine to 800 mg/day, and she was again responsive. She remained pain free at the four-month follow-up. High-resolution MRI revealed the compression of the trigeminal nerve by the superior cerebellar artery, and DTI-MR tractography detected the microstructural effects of this neurovascular compression (Figure 3). FA values for the trigeminal nerves were 0.30 ± 0.029 (mean ± SD) on the right side and 0.34 ± 0.039 (mean ± SD) on the left side. The affected side was lower than the nonaffected side. ADC values were 2.39 ± 0.69 mm2/sec (mean ± SD) on the right side and 2.25 ± 0.13 mm2/sec (mean ± SD) on the left side.

Figure 3

High-resolution magnetic resonance imaging (MRI) axial image demonstates the compression of the right trigeminal nerve by the superior cerebellar artery (arrow) (A). MR tractography delineates the structural changes in the right trigeminal nerve secondary to vascular compression (B). In the fractional anisotropy color map (B), slight darkness (arrowheads) in the right trigeminal nerve is seen secondary to vascular compression when compared with the left side. Fractional anisotropy value was lower on the right side (0.30 ± 0.029 on the right and 0.34 ± 0.039 on the left).

Figure 3

High-resolution magnetic resonance imaging (MRI) axial image demonstates the compression of the right trigeminal nerve by the superior cerebellar artery (arrow) (A). MR tractography delineates the structural changes in the right trigeminal nerve secondary to vascular compression (B). In the fractional anisotropy color map (B), slight darkness (arrowheads) in the right trigeminal nerve is seen secondary to vascular compression when compared with the left side. Fractional anisotropy value was lower on the right side (0.30 ± 0.029 on the right and 0.34 ± 0.039 on the left).

Discussion

The management of SUNCT is challenging, and no abortive treatment is available for the attacks. In the preventive treatment, lamotrigine, topiramate, zonisamide, gabapentin, carbamazepine, and oxcarbazepine are reported to be effective in some SUNCT patients. Lamotrigine as a first drug of choice [7] was not effective in our patients. Our second patient was treated successfully with carbamazepine, and we also added supraorbital and infraorbital nerve blockade for the acute treatment.

Surgery was tried in the first patient who had medically intractable pain, and she was symptom free after the microvascular decompression and she did not suffer from any surgical complications. In a case series of nine SUNCT/SUNA patients [10] who underwent microvascular decompression surgery, six out of nine (67%) patients were reported to have immediate and complete relief of SUNCT and SUNA symptoms and this result was preserved through the follow-up period of nine to 32 months (mean = 22.2 months). Microvascular surgery must be kept in mind as a theurapeutic option in medically refractory SUNCT.

The pathophysiology of SUNCT is not fully understood. However, the activation of the posterior hypothalamus during attacks was demonstrated in functional neuroimaging studies [3]. The compression of the trigeminal nerve may sensitize and activate the trigeminal nucleus caudalis. Activation of the trigeminal nucleus may stimulate the superior salivatory nucleus and the sphenopalatine ganglion and may trigger the trigemino-parasympathetic reflex, leading to autonomic clinical features. The posterior hypothalamus, which has modulatory role on the nociceptive and autonomic pathways, may be activated secondarily, which in return may aggravate the autonomic features. There is building evidence in the literature that shows the neurovascular compression of the trigeminal nerve near the root entry zone. In a series of SUNCT/SUNA patients, neurovascular compression was revealed by MRI in 88% of the patients [2]. Short-lasting attacks of SUNCT/SUNA are likely to be due to ectopic discharges occuring at the zone of focal demyelination caused by vascular compression [11].

The anatomical imaging of the cranial nerves (CNs) is important, from diagnostic and surgical perspectives [12]. DTI and MR tractography are widely used for visualizing nerve bundles by assessing diffusion abnormalities. DTI and MR tractography together can differentiate normal and abnormal nerve tracts by measuring diffusivity or diffusion anisotropy, and changes in the diffusivity or diffusion anisotropy give information about the neural microstructure [12,13]. MR tractography is a feasible method to delineate small fiber bundles in the brainstem. Previously, loss of anisotropy was shown by DTI in trigeminal neuralgia [14].

An increasing amount of literature provides evidence of neurovascular compression in neuroimaging and the benefit of surgical treatments in medically refractory SUNCT/SUNA [2,4,5,7,10]. To our knowledge, this is the first time in the literature where MR tractography revealed microstructural changes in the trigeminal nerve due to neurovascular compression in SUNCT patients. The major limitation is the lack of healthy volunteers as the control group to compare the FA values between the groups. Further studies with healthy controls as the comparison group are needed.

High-resolution MRI and/or DTI-MR tractography should be performed to exclude neurovascular compression of the trigeminal nerve in SUNCT patients. The etiology and pathogenesis of SUNCT is not enlightened yet. However, the compression of the trigeminal nerve seems to generate SUNCT symptoms and may cause the activation of the posterior hypothalamus, which may augment the autonomic symptoms. This perspective brings up the idea that trigeminal neuralgia and SUNCT may be two different presentations of the neurovascular compression syndrome of the trigeminal nerve.

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Author notes

Conflicts of interest: The authors declare no conflicts of interest.