Responsiveness of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing to hypothalamic deep brain stimulation

Case report

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Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a severe primary headache disorder that is often refractory to medical therapy. Although the pathogenesis of this and other trigeminal autonomic cephalalgias is not completely understood, ipsilateral activation of the posterior and inferior hypothalamus has been identified on functional imaging studies during attacks. The authors report on a case of SUNCT syndrome successfully treated with hypothalamic deep brain stimulation and discuss the current literature.

Abbreviations used in this paper: DBS = deep brain stimulation; SUNCT = short-lasting unilateral neuralgiform headache with conjunctival injection and tearing; TAC = trigeminal autonomic cephalalgia.

Abstract

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a severe primary headache disorder that is often refractory to medical therapy. Although the pathogenesis of this and other trigeminal autonomic cephalalgias is not completely understood, ipsilateral activation of the posterior and inferior hypothalamus has been identified on functional imaging studies during attacks. The authors report on a case of SUNCT syndrome successfully treated with hypothalamic deep brain stimulation and discuss the current literature.

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing is a rare primary headache disorder that is often refractory to medical and surgical treatment. It belongs to a family of headache disorders known as TACs, which includes cluster headache.3 The disorder is characterized by excruciating paroxysms of strictly unilateral orbitotemporal headache lasting seconds to minutes and recurring up to 200 times per day, and is one of the most painful conditions known. The only medications shown to have some effectiveness in isolated cases of SUNCT are topiramate, lamotrigine, intravenous lidocaine, and gabapentin.2 Increased blood flow in the posterior hypothalamus has been documented during attacks of SUNCT on functional MR imaging.11 Leone and colleagues6 reported on a patient with SUNCT who was successfully treated with hypothalamic DBS. We report on the first patient in North America treated for SUNCT with ipsilateral hypothalamic DBS.

Case Report

History and Examination

This 44-year-old man presented with a 36-year history of SUNCT. He began experiencing ~ 10–20 attacks per month at the age of 8 years. At age 14, the attacks began to increase in frequency, and by age 34, the attacks became a daily occurrence. At presentation, the average number of attacks the patient was experiencing was ~ 120 per day (range of 30–200). These lasted ~ 60–120 seconds, and every attack was associated with lacrimation, conjunctival injection, and rhinorrhea. The attacks occured throughout the 24-hour day and included nocturnal attacks that frequently awakened the patient from sleep. Vomiting, ipsilateral visual blurring, and photophobia could occur prior to or during an attack. There was no refractory period between attacks.

The patient's condition failed to respond to therapeutic doses of lamotrigine, topiramate, divalproex sodium, gabapentin, zonisamide, levetiracetam, pregabalin, duloxetine, botulinum toxin Type A injections, ipsilateral occipital nerve block, amitriptyline, propranolol, indomethacin, verapamil, venlafaxine, intravenous histamine, intravenous and oral corticosteroids, cyproheptadine, rizatriptan, frovatriptan, sumatriptan, methergine, dihydroergotamine, testosterone, and pergolide. Intravenous infusions of lidocaine resulted in complete cessation of attacks during the infusion but recurrence occurred within 72 hours after discontinuing the infusion.

On examination, pertinent findings included hypesthesia to pinprick, temperature, and light touch over all 3 divisions of the left trigeminal nerve; corneal reflexes were present. The neurological examination was otherwise normal. Magnetic resonance imaging of the brain with a 3D volume series through the posterior fossa and coronal dynamic Gd-enhanced series and high-resolution T2-weighted scans through the sella was normal. The complete blood count, serum chemistry, sensitive thyroid stimulating hormone, prolactin, testosterone, growth hormone, serum cortisol levels were all within normal limits.

Operation and Postoperative Course

The patient asked to be considered for DBS surgery, and after institutional review board approval had been obtained, he underwent ipsilateral hypothalamic microelectrode recording and microstimulation followed by implantation of a DBS electrode (Model 3389S, Medtronic). A stereotactic headframe (COMPASS) was placed and MR images of 1-mm slice thickness were obtained in a Philips MR scanner. Our targeting was based on calculation of the anterior–posterior commissure line. We used coordinates of 3-mm posterior to and 5-mm inferior to the anterior–posterior commissure line as planned on 3D MR imaging with the COMPASS stereotactic system. The lead was placed 2-mm lateral to the ipsilateral wall of the third ventricle. Intraoperative microelectrode recordings showed only sparse, irregular brief neuronal firing. Intraoperative micro- and macrostimulation was performed to discover unwanted or unacceptable side effects. Final electrode placement was determined based on a combination of MR target planning and stimulation effects (Fig. 1).

Fig. 1.
Fig. 1.

Coronal (upper) and axial (lower) T-1 weighted MR images demonstrating the DBS lead in the posterior medial hypothalamus.

The following parameters were used in the initial programming: case (+), contact 0 (−), 1.4 V, 60 microseconds, and 185 Hz. The month before surgery the patient had had an average of 133 attacks per day. During the first month after DBS, he had an average of 45 headaches per day, with as few as 4 attacks. At 6 months post-DBS, he had an average of 46 attacks per day. At 9 months post-DBS, he continued to improve with an average of 33 headaches per day. At 12 months post-DBS, his mean headache frequency was 25 attacks per day. He is currently not receiving preventative therapy for SUNCT but intermittently uses 50-mg intramuscular diphendydramine to decrease the intensity of the daily attacks. His most recent pulse generator settings were case (+), contact 0 (−), 1.4 V, 90 microseconds, and 160 Hz. The primary side effect of long-term stimulation was significant erectile dysfunction. The patient also reported jaw pulling and leg jerking on using contacts 0 and 1 (−) and case (+).

Discussion

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing headache syndrome is a consuming and severely debilitating disease. It is a rare problem and is unfortunately extremely difficult to treat effectively.1,8,13 The important work by Leone et al.4–7 has helped to develop a surgical option for patients with medically refractory SUNCT and cluster headache. The posterior inferior hypothalamus target was developed in part due to functional MR imaging demonstrated activation in this area during headache attacks, similar to that seen during cluster headache attacks.9–11 Hypothalamic stimulation has been reported in the literature to result in significant improvement in patients with cluster headaches refractory to medical therapy.4,5,7 Leone et al.6 recently reported on a single case of SUNCT headaches that responded to hypothalamic DBS.

Our patient had a 36-year history of medically refractory SUNCT with a mean of 120 attacks per day. After ipsilateral hypothalamic DBS, the patient experienced an immediate 63% decrease in the mean number of attacks per day, and a progressive decline in attack frequency such that by the 12th postoperative month, he experienced an 80% reduction in daily attack frequency and is not concurrently taking prophylactic therapy. This response is somewhat different than the case described by Leone and colleagues6 in which the response was delayed but rather abrupt and was complete after ~ 6 months of stimulation. Our patient experienced consistent but not immediate relief or exacerbation when the stimulator was turned on and off, respectively.

The causes of SUNCT syndrome may be similar to that of cluster headache attacks although the underlying pathogenesis is not well understood. The lack of improvement seen in patients after trigeminal denervation procedures and ipsilateral hypothalamic activation are strong evidence that the attacks are centrally generated.1 Although it is not known how stimulation of the presumed generator effectively prevents attacks from occurring, a recent positron emission tomography study of 10 patients who had undergone hypothalamic DBS for cluster headache demonstrated both activation and deactivation in cerebral structures that comprise the neural pain matrix known to be activated during cluster headache attacks.12 These findings suggested that rather than inhibiting ipsilateral activity in the presumed generator, hypothalamic DBS may result in functional modulation of the pain neural matrix.

The long-term durability, patient tolerance, and adverse event profile of this procedure for the treatment of medically refractory SUNCT is not clear. Careful monitoring of patients who undergo this procedure for the treatment of SUNCT and other primary headache disorders will be crucial, particularly given the few patients with this rare disorder who will ultimately undergo the procedure. Although this procedure may not be curative, ipsilateral hypothalamic DBS may offer a new and effective treatment for this severe form of medically resistant headache.

Conclusions

Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing is a rare, debilitating, and poorly responsive disease. Similar to other TACs, it is known to be associated with ipsilateral hypothalamic activation. Although our patient had a positive response to DBS hypothalamic stimulation, it is very important to be aware that this case represents a single patient in an uncontrolled study and that his response was partial. As debilitating as this condition is, it is essential to remain cautious when interpreting the results of a single patient's response to treatment. Further study into the mechanism of TAC headaches is necessary. Given the frequency of headache attacks in patients with SUNCT, this entity may lend itself well to ictal electroencephalography with functional MR and/or positron emission tomography imaging. These modalities could be combined with the subtraction ictal single photon emission CT coregistered to MR technology currently used in some epilepsy units for foci localization. Response to stimulation parameters may be able to be coregistered to imaging data sets. Ipsilateral hypothalamic DBS may offer a new, effective treatment for this severe form of medically resistant headache.

Disclaimer

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Please include this information when citing this paper: published online September 26, 2008; DOI: 10.3171/2008.4.17493.

References

  • 1

    Black DFDodick DW: Two cases of medically and surgically intractable SUNCT: a reason for caution and an argument for a central mechanism. Cephalalgia 22:2012142002

  • 2

    Cohen ASMatharu MSGoadsby PJ: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA)–a prospective clinical study of SUNCT and SUNA. Brain 129:274627602006

  • 3

    Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders: 2nd edition. Cephalalgia 24:91602004

  • 4

    Leone MFranzini ABroggi GMay ABussone G: Longterm follow up of bilateral hypothalamic stimulation for intractable cluster headache. Brain 127:225922642004

  • 5

    Leone MFranzini ABussone G: Stereotactic stimulation of posterior hypothalamic gray matter for intractable cluster headache. N Engl J Med 345:142814292001

  • 6

    Leone MFranzini AD'Andrea GBroggi GCasucci GBussone G: Deep brain stimulation to relieve drug-resistant SUNCT. Ann Neurol 57:9249272005

  • 7

    Leone MMay AFranzini ABroggi GDodick DRapoport A: Deep brain stimulation for chronic intractable cluster headache: proposals for patient selection. Cephalalgia 24:9349372004

  • 8

    Matharu MSCohen ASBoes CJGoadsby PJ: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing syndrome: a review. Curr Pain Headache Rep 7:3083182003

  • 9

    May ABahra ABuchel CFrackowiak RSGoadsby PJ: Hypothalamic activation in cluster headache attacks. Lancet 352:2752781998

  • 10

    May ABahra ABuchel CFrackowiak RSGoadsby PJ: PET and MRA findings in cluster headache and MRA in experimental pain. Neurology 55:132813352000

  • 11

    May ABahra ABuchel CTurner CGoadsby PJ: Functional MRI in spontaneous attacks of SUNCT: short-lasting unilateral neuralgiform headache with conjunctival injection and tearing. Ann Neurol 46:7917931999

  • 12

    May ALeone MBoecker HSprenger TJuergens TBussone G: Hypothalamic deep brain stimulation in positron emission tomography. J Neurosci 26:358935932006

  • 13

    Pareja JAKruszewski PSjaastad O: SUNCT syndrome: trials of drugs and anesthetic blockades. Headache 35:1381421995

Article Information

Address correspondence to: Mark K. Lyons, M.D., Department of Neurological Surgery, Mayo Clinic Arizona, 5777 East Mayo Boulevard, Phoenix, Arizona 85054. email: lyons.mark2@mayo.edu.

© AANS, except where prohibited by US copyright law.

Headings

Figures

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    Coronal (upper) and axial (lower) T-1 weighted MR images demonstrating the DBS lead in the posterior medial hypothalamus.

References

1

Black DFDodick DW: Two cases of medically and surgically intractable SUNCT: a reason for caution and an argument for a central mechanism. Cephalalgia 22:2012142002

2

Cohen ASMatharu MSGoadsby PJ: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or cranial autonomic features (SUNA)–a prospective clinical study of SUNCT and SUNA. Brain 129:274627602006

3

Headache Classification Subcommittee of the International Headache Society: The International Classification of Headache Disorders: 2nd edition. Cephalalgia 24:91602004

4

Leone MFranzini ABroggi GMay ABussone G: Longterm follow up of bilateral hypothalamic stimulation for intractable cluster headache. Brain 127:225922642004

5

Leone MFranzini ABussone G: Stereotactic stimulation of posterior hypothalamic gray matter for intractable cluster headache. N Engl J Med 345:142814292001

6

Leone MFranzini AD'Andrea GBroggi GCasucci GBussone G: Deep brain stimulation to relieve drug-resistant SUNCT. Ann Neurol 57:9249272005

7

Leone MMay AFranzini ABroggi GDodick DRapoport A: Deep brain stimulation for chronic intractable cluster headache: proposals for patient selection. Cephalalgia 24:9349372004

8

Matharu MSCohen ASBoes CJGoadsby PJ: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection, tearing syndrome: a review. Curr Pain Headache Rep 7:3083182003

9

May ABahra ABuchel CFrackowiak RSGoadsby PJ: Hypothalamic activation in cluster headache attacks. Lancet 352:2752781998

10

May ABahra ABuchel CFrackowiak RSGoadsby PJ: PET and MRA findings in cluster headache and MRA in experimental pain. Neurology 55:132813352000

11

May ABahra ABuchel CTurner CGoadsby PJ: Functional MRI in spontaneous attacks of SUNCT: short-lasting unilateral neuralgiform headache with conjunctival injection and tearing. Ann Neurol 46:7917931999

12

May ALeone MBoecker HSprenger TJuergens TBussone G: Hypothalamic deep brain stimulation in positron emission tomography. J Neurosci 26:358935932006

13

Pareja JAKruszewski PSjaastad O: SUNCT syndrome: trials of drugs and anesthetic blockades. Headache 35:1381421995

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