A case of atypical sporadic hemiplegic migraine associated with PFO and hypoplasia of vertebro-basilar system

In our case some of the clinical features of the aura (dysarthria, diplopia, dizziness etc.) during attacks were expression of brainstem dysfunction, so fulfilling the criteria for diagnosis of basilar-type migraine (ICHD-II) [2]. However, the presence of the motor weakness (consistent across attacks) and the length of the aura (more than 1 week), made the inclusion in this nosographic category inadequate. Indeed, according to the last International Classification of Headache Disorders 2nd Edition revision (ICHD-II) [2], basilar-type migraine should be diagnosed only when no motor weakness occurs; therefore the diagnosis of sporadic hemiplegic migraine (no familial history of migraine in our patient) could appear more appropriated, even if the lack of visual or sensory symptoms makes diagnosis very puzzling. Moreover the slow resolution of the motor aura that went beyond 24 h could be interpreted as “persistent aura without infarction” and the attacks classifiable as “probable migraine with aura”. Namely, repeated neuroimaging examination excluded ischemic damage or other cerebral pathologies underlying symptoms.

Familial hemiplegic migraine has basilar-type symptoms in 60% of cases and recently a novel mutation in the ATP1A2 gene (R548H) in members of a family with BTM has been detected, suggesting that BTM and familial hemiplegic migraine (FHM) may be allelic disorders [7, 8]. The most intriguing aspect in our case was the presence of a large PFO. Several data in literature indicate an increased incidence of PFO in MA patients compared with general population [9, 10]. A closure of PFO in patients with transient cerebral ischemia suffering from MA induced an improvement of MA episodes [11]. However, the role of PFO in migraine pathogenesis remains to be established and, based on the recently published MIST trial data [12], there is no sufficient evidence that recurrence of migraine is improved by PFO closure.

On such basis, in the present case the 4-year persisting remission of migraine cannot be convincingly attributed to the PFO closure. Similarly, taking the natural history of hemiplegic migraine also into account, notoriously difficult to predict, it is not obvious to establish a causal link between PFO re-opening and attack relapsing. Nevertheless, it cannot be excluded that, in our patient, PFO plays a role, at least as cofactor, in the complex pathogenetic mechanisms of migraine.

Finally, it is interesting to note that our patient also had a marked hypoplasia of the basilar artery. There is a causal relationship between these conditions or is the association just coincidental?

It is worth noting that in our patient, symptoms of brain-stem dysfunction were consistent across all attacks.

Since the original description of Birkerstaff [13] that attributed the brainstem dysfunction in BTM to the “constriction” of the basilar artery, “reversible vertebro-basilar ischemia” has been described in patients with BTM and FHM [14, 15]. Recently, it has been reported in a case of basilar artery fenestration and hypoplasia of the right posterior cerebral artery in a woman with basilar-type migraine [16]. About the possible role of basilar artery stenosis, it is to be noted that a higher frequency of hypoplastic vertebral artery (VA) was found in MA [17]. The authors suggested that hypoplasia of VA may be an additional factor leading to hypoperfusion in the posterior circulation during the aura phase. More recently Chuang et al. hypothesized that VA hypoplasia contributes to migraine trough complex neurovascular pathways rather than trough its low-flow volume [18].

Although vascular mechanisms are recently considered less relevant in migraine pathogenesis, vascular factors could play a role in some phases of the cascade underlying the migraine attack. The question remains open.