Abstract
Background and objectives
We describe a case of a female patient whose otherwise “typical” migraine attacks turned into episodes with a full spectrum of associated symptoms but without headache.
Case report
We evaluated a 53-year-old woman with a long history of migraine without aura. In concomitance with premenopausal menstrual dysregulation, she reported episodes of nausea and vomiting, associated with photophobia, phonophobia and osmophobia, but without headache; these episodes were responsive to oral triptans. Alternative diagnoses were excluded through extensive examinations.
Discussion
To date, no reports have been published in the literature on otherwise typical migraine attacks that are not accompanied by headache, nor did our case seem comparable to cases of abdominal migraine and cyclic vomiting syndrome.
Conclusion
Pathophysiologically, we hypothesize that functional dysregulation of the hypothalamus-brainstem connectivity may generate migraine attacks with a full spectrum of associated symptoms but without pain.
Background and objectives
Migraine is a complex disorder, with phenotypic variability occurring within the same individual and especially among different individuals (1). This heterogeneity involves both migraine attacks (features such as localisation, lateralisation, quality and intensity of pain, presence or absence of premonitory and accompanying symptoms, and the occurrence of aura) and migraine as a “chronic disease” (differences related to age, gender, reproductive life, comorbidities, and evolution over time).
In the present work, we describe a case of a female patient whose otherwise “typical” migraine attacks turned into migraine attacks with a full spectrum of associated symptoms but without headache.
Case report
A 53-year-old woman was seen at our Headache Centre in May 2016. She had complained of migraine without aura (MwoA) since the age of 16. She reported unilateral, pulsating, severe headache attacks, associated with photophobia, phonophobia, osmophobia, nausea, and occasional vomiting. Her attacks, for which she herself recognised some migraine triggers (such as the weekend, and menstrual windows), were successfully treated with oral triptans (sumatriptan 100 mg or rizatriptan 10 mg) as abortive therapy.
The patient had a family history of MwoA (her mother and a sister); her past medical history was otherwise unremarkable and notably did not include the so-called “childhood periodic syndromes” (2).
In November 2015, in concomitance with premenopausal menstrual dysregulation, the patient began to report episodes of nausea and frequent vomiting, associated with photophobia, phonophobia, osmophobia, but without headache. Just like her “typical” migraine attacks, these episodes lasted one to three days when untreated; they responded well to oral triptans, but not to common antiemetic agents (metoclopramide and domperidone). The reported triggers and the frequency of attacks (2–3 per month) were similar to the previous migraine attacks.
The patient also reported some residual but infrequent “typical” migraine attacks with headache. At our first observation, we performed extensive neurological and general examinations, which were completely normal.
Alternative diagnoses and diagnostic workout.
Nowadays, the patient remains under strict follow-up. Preventive therapy was not necessary, due to the low frequency of episodes and the efficacy of symptomatic treatment with oral triptans.
Discussion
To date, no reports have been published in the literature on typical migraine attacks that are not accompanied by headache. The possibility of a primary headache with a full spectrum of associated symptoms but without pain has been described only for cluster headache (3); on the other hand, it is well known (2) that migraine with aura may not be associated with headache.
Extensive differential diagnosis was considered in our case, but the examinations indicated in Table 1 allowed us to rule out any underlying disorders.
Among primary headache disorders, the current ICHD 3 beta classification (2) recognises some syndromes that are historically known to occur in childhood (previously described as “childhood periodic syndromes”), but which also occur in adults including, among others, recurrent gastrointestinal disturbance (i.e. abdominal migraine and cyclic vomiting syndrome).
Our case did not seem comparable to cases of abdominal migraine due to the absence of the typical bouts of abdominal pain (4).
On the other hand, we did find some similarities to cyclic vomiting syndrome (CVS), namely: (a) CVS has been reported to occur in adults in various case series (5,6); (b) a personal or a family history of migraine headache is common (7); (c) associated symptoms are frequent, including phonophobia and photophobia, even if pallor and lethargy are more common (7); (d) triptans are an effective acute therapy in some patients – sumatriptan nasal spray or subcutaneous sumatriptan are the most widely used (8), but successful treatment with oral sumatriptan has also been reported (9).
Nevertheless, there were also significant differences: (a) age at onset in adults with CVS is younger than in our case, and sometimes CVS may continue from childhood (7); (b) CVS is known to recur with a predictable pattern (2), while in our case a similar periodicity was clearly related to previous migraine triggers, although menstruation has also been reported as a CVS trigger (5,7); (c) in our case, the features of each attack were not clearly stereotyped as in CVS (2) (for example, some attacks occurred without vomiting, and there were residual migraine attacks with headache); (d) vomiting occurs in CVS with a very high median frequency of six times/hour (7), while in our case the episodes of nausea and vomiting were isolated; (e) contrary to their reported efficacy in CVS, antiemetic agents were not effective in our case (7).
A few pathophysiological considerations can be made. A recent functional imaging study (10) suggests that migraine might be the result of a functional change in hypothalamus-brainstem connectivity. Moulton and colleagues (11) advanced the hypothesis that changes in hypothalamic connections to autonomic circuits and the locus coeruleus may be responsible for the occurrence of autonomic symptoms in migraine attacks.
On the other hand, several functional imaging studies have found that brainstem areas located in the dorsal midbrain and the rostral dorsolateral pons are active during migraine pain (12). Candidate nuclei include the dorsal raphe nucleus, the periaqueductal gray and the locus coeruleus nucleus, which modulate nociception through projections to the spinal trigeminal complex and regulate cerebral blood flow (12).
Based on such evidence, the hypothalamus may be a generator of premonitory and accompanying migraine symptoms, while the brainstem may be a generator of pain. Our case highlights the possibility that a functional dysregulation of hypothalamus-brainstem circuitry, presumably triggered by hormonal changes, may be the origin of migraine attacks with a full spectrum of associated symptoms, but without pain.
Clinical implications
This is the first literature report of migraine attacks with a full spectrum of associated symptoms but without headache. The presence of recurrent episodes of nausea and vomiting in adult patients requires an extensive differential diagnosis, including so-called recurrent gastrointestinal disturbance (i.e. abdominal migraine and cyclic vomiting syndrome). Migraine-associated symptoms and pain may have two different neural generators (i.e. the hypothalamus and the brainstem, respectively), which may be functionally decoupled under certain conditions (such as premenopausal menstrual dysregulation).
Footnotes
Declaration of conflicting interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.