Cohen, A.S.; (2006) Functional imaging in primary headache syndromes: focus on Trigeminal Autonomic Cephalgias. Doctoral thesis , University of London.

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Abstract

SUNCT (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing) and SUNA (Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms) are rare primary headache syndromes, classified with the Trigeminal Autonomic Cephalgias (TACs). Hypothalamic involvement in SUNCT and other TACs has been suggested by functional imaging data and clinically with successful deep brain stimulation. This thesis studies 52 patients (43 SUNCT, 9 SUNA). It addresses the clinical phenotype of these conditions and response to medications. A functional imaging study explores activation of the posterior hypothalamus in attacks of SUNCT and SUNA, and looks for structural changes in this region on voxel-based morphometry. The clinical study characterises SUNCT and SUNA in terms of epidemiology of the syndromes, phenotype and clinical characteristics. A double-blind trial of topiramate in SUNCT showed a 40% response rate, although a similar trial in lamotrigine was less successful. Indomethacin is ineffective in these conditions on single-blind testing. Intravenous lidocaine was effective in all cases. Open- label trials showed the effectiveness of lamotrigine, topiramate and gabapentin. On functional imaging there was activation bilaterally in the posterior hypothalamus in 5/9 SUNCT patients, and contralaterally in two patients. Two SUNCT patients had ipsilateral negative activation. In SUNA the activation was bilaterally negative. Group analysis showed bilateral activation, although there was no such activation on whole brain analysis. There was no structural change in this region on voxel-based morphometry. The thesis concludes that there should be revised classification for SUNCT and SUNA, with an increased range of attack duration and frequency, cutaneous triggering of attacks, and a lack of refractory period. The concept of 'attack load' is introduced. The lack of response to indomethacin, and the response to intravenous lidocaine, are useful in diagnostic and therapeutic measures respectively. Preventive treatments include lamotrigine, gabapentin and topiramate. Hypothalamic activation is discussed in light of the imaging and methodological issues. Finally the role of hypothalamic involvement in SUNCT and SUNA as TACs is considered.

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