From neuroimaging to patients’ bench: what we have learnt from trigemino-autonomic pain syndromes

Abstract

Trigeminal autonomic cephalalgias (TACs) are primary headaches including cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). A number of neuroimaging studies have been conducted in last decade showing involvement of brain areas included in the pain matrix. Apart from pain matrix involvement, other neuroimaging findings data deserve special attention. The hypothalamic activation reported in the course of TAC attacks coupled with the efficacy of hypothalamic neurostimulation to treat drug-resistant TAC forms clearly indicate the posterior hypothalamus as a crucial area in TAC pathophysiology. In animal models this brain area has been shown to modulate craniofacial pain; moreover, hypothalamic activation occurs in other pain conditions, suggesting that posterior hypothalamus has a more complex role in TAC pathophysiology rather than simply being considered as a trigger. In contrast, hypothalamic activation may serve as a crucial area in terminating rather than triggering attacks. It also could lead to a central condition facilitating initiation of TAC attacks.

Cluster-like headache and a cystic hypothalamic tumour as first presentation of sarcoidosis

“…Other structural lesions were meningiomas, aneurysms of the right or left carotid arteries, arteriovenous malformations and two separated cases of a gangliocytoma and a nasopharynx carcinoma respectively (12,13). To our knowledge, lesions solely confined to the hypothalamus associated with TACs and cluster-like headaches have not been reported so far, even though lesions originating in its vicinity and compressing the hypothalamus, or other structures of the above described regulatory system, the so-called pain matrix (9,10), have been described (11,14). We cannot rule out that the finding of neurosarcoidosis in the hypothalamus is a coincidental diagnosis.…”

“…The hypothalamus is probably also the origin of the signs of unilateral sympathetic dysfunction like ptosis and miosis (7). The hypothalamus seems to play a central role in the complex regulatory system of TACs, although its role as the primary causative agent in these headaches is still disputed (7)(8)(9)(10).…”

A boy with bilateral SUNA: A case report

“…Neuroimaging studies have substantially advanced our understanding of the mechanisms underlying primary headache syndromes. Functional neuroimaging studies in trigeminal autonomic cephalalgias, including SUNA, report specific activation of the hypothalamus in association with the headaches (10). Furthermore, structural imaging studies report that a significant proportion of patients have an aberrant vascular loop in contact with the ipsilateral trigeminal nerve (11), like neurovascular contact can be found in patients with trigeminal neuralgia (12).…”