Hemicrania continua exacerbations with prodromal burping as a potential autonomic symptom

Although some studies suggest hemicrania continua (HC) is underdiagnosed rather than rare, representing approximately 1.7% of headache clinic patients,1 we believe this to be the first reported case of HC exacerbations presenting with burping. We propose burping as a potentially unrecognized autonomic symptom of HC and outline a mechanistic hypothesis grounded in recent advances in human neuroanatomy. A comprehensive literature review identified only two articles documenting the co-occurrence of burping and cluster headache (CH), but none regarding HC. One study2 describes burping in CH as a common and often disregarded accompanying symptom of the classic autonomic features, whereas the other mentions a CH case3 associated with burping that, interestingly, responded to indomethacin. We present this case of HC with associated burping as a potential autonomic symptom with the written informed consent of the patient. A 59-year-old woman was referred to Neurology. She reported having a constant background headache that started 6 years prior. In the last 3 years, she developed exacerbations, which had worsened in frequency, duration, and severity in the 6 months leading to referral. Immediately prior to the onset of an exacerbation, she began burping continuously. The headache exacerbations were localized above the right eye and consisted of 15-min spells of sharp, profoundly severe pain, leaving her rocking, and did not cease until the burping did. These were followed by a less severe throbbing pain for around 5 days on average, and 10 days at its longest, before returning to her longstanding background headache. She reported trying to sleep off the headaches in a dark room with no success. The severe headache episodes were also accompanied by right-sided lateralization of lacrimation, clear rhinorrhea, photophobia and phonophobia, but no nausea or limb symptoms. She experienced around three to four of these episodes monthly. She reported partial relief with sumatriptan nasal spray during exacerbations. She could not identify any triggers. Over the years, her general practitioner (GP) queried if her presentation was migraine, so she was trialed on oral sumatriptan, acetaminophen, naproxen, and amitriptyline prophylaxis with no effect. Her past medical history included hiatus hernia, depression, and mild aortic stenosis, and she was not taking any regular medication. She did not drink alcohol but smoked 20 cigarettes per day. She was not working due to her current issues. Physical examination and routine laboratory tests were unremarkable. She had two MRI head scans—one approximately 1 year after headache onset and a second one several months after the headaches' worsening, both of which were normal. C-reactive protein was within normal range, and the patient had mild thrombocytosis for over a decade, which was investigated by Hematology, with no cause identified. It was agreed to treat as hemicrania continua, with indomethacin 25 mg 3 times daily, aiming to reduce to the lowest effective dose. Gastroprotection was also advised, in the form of omeprazole 20 mg daily. The patient reported that, within 2 days of treatment with indomethacin, the constant headache and exacerbations accompanied by burping fully resolved. She reduced the dose to 25 mg twice daily and reported that lower doses led to her waking up with headaches. She was discharged from the open follow-up list 1 year later because no further input was required. The patient is meeting all the required criteria for diagnosing hemicrania continua.4 Two differentials that have been considered are migraine and CH. Although indomethacin is an NSAID and migraine can also respond to this class of medications, it is noteworthy that the patient did try naproxen as well with no effect. Moreover, in line with the International Classification of Headache Disorders, 3rd edition, criterion that symptoms should not be better accounted for by another diagnosis, the constant background headache, the absolute response to indomethacin, and the lateralization of associated autonomic symptoms, we concluded HC as the more likely diagnosis. We do acknowledge, however, that multiple headache disorders can coexist. Given the overlap in timing between the burping and the other autonomic symptoms during the exacerbations, we hypothesize that it could be an autonomic symptom in HC. Notably, the patient reported no other burping episodes in between headaches. Nevertheless, we wanted to ensure the burping was not better linked to other causes, such as hiatal hernia, or potentially undiagnosed gastroesophageal reflux disorder or functional dyspepsia. Upon reviewing her whole medical history, the hiatal hernia appears as a historical diagnosis from 17 years previously, following an endoscopy for weight loss. Burping had not been reported until the headaches worsened; she denied any other gastrointestinal symptoms and did not feel it was influenced by alterations in her diet. H pylori stool antigen and celiac serology were negative. The GP had trialed her on omeprazole, which did not help. On the other hand, indomethacin not only fully stopped all her symptoms but would have been expected to worsen any preexisting gastrointestinal issues, which might have been contributing to burping. Whereas burping can be a common psychosomatic symptom, there were no identifiable emotional stressors that could have acted as a trigger. Most importantly, the hallmark feature of psychosomatic conditions, inconsistency, is also lacking—there was no variability in the symptoms reported—the patient's burping was consistently and tightly linked to her headache exacerbations. Taking all these into consideration, we believe that burping in this case reflects autonomic nervous system dysregulation rather than simple locally originating gastrointestinal reflexes resulting in burping. Although the pathogenesis of trigeminal autonomic cephalalgias is not fully understood, one proposed mechanism involves trigeminal nerve autonomic dysregulation, resulting in increased parasympathetic outflow and reduced sympathetic system activity.5 Via vagal pathways, this imbalance could lead to heightened gastrointestinal activity (stimulating the diaphragmatic muscles and relaxing the esophageal sphincter), resulting in air expulsion as burping. We hypothesize this reflex could be likened to the mammalian diving reflex, where the trigeminal nerve acts as the afferent and the vagus nerve as the efferent. This synergy could be explained by trigeminovagal fibers intertwining. Although such a system—trigeminovagal—has been mostly reported in animal studies, one ex vivo study6 successfully found an anatomical intertwining of the vagal and trigeminal fibers in humans: the vagal fibers intersect the spinal trigeminal nucleus—specifically the caudal subnucleus, and the spinal trigeminal tract, in the lateral rostral medulla; the vagal fibers then continue further, dorsally in area postrema, which is known to be involved in the mechanism of burping.7 Specifically, area postrema modulates the excitability of the nucleus tractus solitarius, which then communicates with the dorsal motor nucleus of the vagus, providing parasympathetic motor output, via the vagus nerve, to the stomach and lower esophageal sphincter. Given the diagnosis of HC, the interesting feature of this case is that the exacerbations were clearly marked by prodromal burping, which continued alongside the usual autonomic symptoms for the duration of the exacerbation. This raises the question of whether burping could represent a possible autonomic symptom in HC. Clinicians may need to consider and actively ask about this when assessing and diagnosing HC because the reporting of further case studies on similar presentations will aid collecting sufficient data to review the validity of our observation. To the best of the authors' knowledge, this is the first reported case of HC with burping as a prominent autonomic symptom. Raluca A. Negulescu: Investigation; methodology; writing – review and editing; writing – original draft; resources; conceptualization; supervision. Michael O'Gara: Conceptualization; methodology; writing – review and editing; writing – original draft; supervision; investigation; resources. The authors would like to thank Dr. Oliver Bendall for his invaluable guidance and expertise on the gastrointestinal aspects of this case. Raluca Negulescu and Michael O'Gara declare no conflicts of interest.