The pathophysiology of the trigeminal autonomic cephalalgias, with clinical implications

The hallmark of primary headaches belonging to the group known as the trigeminal autonomic cephalalgias is unilateral headache accompanied by cranial autonomic symptoms. Being relatively rare and poorly understood, they represent a clinical challenge, leading to underdiagnosis and undertreatment. While the headache is the most obvious and disabling symptom, it is only part of a complex symptomatology which hints at the involved pathophysiological mechanisms. Activation of the trigeminal-autonomic reflex results in the aforementioned cranial autonomic symptoms, which are well understood; however, it is obvious that this brainstem reflex is regulated by higher centers that seemingly play a pivotal role in the attacks and the wide range of other symptoms indicating a homeostatic disturbance. These symptoms, as well as a number of well-validated findings, implicate the hypothalamus in the pathophysiology. over the course of the past 2-3 decades, novel therapies and technological advances have helped increase our knowledge of these clinical syndromes, and will likely continue to do so in the coming years as we witness the arrival of new drugs and neurostimulation options. In this review, the clinical presentation for cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing, and hemicrania continua is covered, along with our current understanding of the common pathophysiology and clinical manifestations.