Is there any connection between history of immune system disorder (overactive immune system) and either migraine or cluster headaches that don t respond to typical preventative treatments by neurologists? My son, now age 25, has daily, frequently very severe headaches. He s been treated by pain specialists and neurologists with various preventatives (beta blocker, calcium channel blocker, amitriptyline, carbamazapine, topiramate, BOTOX injections on head, occipital nerve block) to no real effect. MRI of brain shows no significant abnormality now, though he had type 1 chiari as a child, no longer apparent (possibly atrophied). As a child, he was diagnosed with periodic fever with aphthous ulcer syndrome , was hospitalized twice for several days each due to severity, was studied by UCLA trying to understand causes, and was treated effectively only by prednisone. During outbreaks, his various measures of inflammation was very high. We were told his immune system was overactive and causing the sores. Is it possible that the headaches are some kind of manifestation of his immune system attacking the nerves that cause the pain? We have tried seemingly everything.