From a neurophysiological perspective, the auras accompanying HM attacks, including the motor ones, are triggered by CSD [8]. This phenomenon might acti­vate the trigeminal nerve at a peripheral level and provoke headaches [9]. CSD may be succeeded by vascular changes and the production of proinammatory mole­cules, leading to a state of parenchymal inammation with the opening of pannexin­ 1 channels and inammasome activation [8]. The motor weakness that can develop into hemiplegia in HM attacks is possibly the result of a prolonged aura since the same patient can have typical FHM attacks interspersed with attacks of non­hemiplegic migraine with aura (MA) [8, 9].

The propagation of CSD reaching the corticostriatal regions could explain the severe motor decits in FHM1 [10]. During CSD, an increase in Ca2+ con­centration in cortical neurons is observed, which is expected with a gain-of­function mutation of Cav2.1 in pyramidal cells [10]. There is an increase in oxygen consumption and a consequent reduction in tissue O2 during vigorous CSD [10]. In these experimental models, multiple CSDs may occur more fre­quently in homozygous models than in heterozygous ones [10]. In FHM1, it is possible to observe glutamatergic changes while the GABAergic release is unal­tered [10]. In addition, specialized core microcircuits of inhibitory interneurons may be involved and responsible for maintaining the excitatory–inhibitory bal­ance pathways necessary to transfer information while preventing runaway excitation [10]. These microcircuits are essential for the correct processing of sensory information (control of sensory gain, suppression, synchronization and generation of cortical rhythms, formation of cell assemblies, and transfer of information to higher areas) [1]. They are likely dysfunctional in FHM, leading to alterations in cortical function and contributing to the development of FHM [1].

The patient’s mother has suffered from migraine with visual aura and sensation of loss of muscle strength since she was 12years old. The patient had no history of seizures. In the rst attack, she was hospitalized and underwent magnetic resonance imaging (MRI) and arterial and venous phase magnetic resonance angiography (MRA) with no abnormal ndings. Lumbar puncture and transcranial Doppler showed no abnormalities. Autonomic system disorders were investigated using a tilt table test, but no abnormalities were found. Hematological and metabolic/endocri­nological tests were all normal. The patient underwent a genetic study that revealed alterations in the CACNA1A gene and was subsequently diagnosed with FHM1. She started calcium channel blockers (unarizine) as a prophylactic treatment. In 6months, she had three moderate-intensity attacks and one of greater magnitude with hemiparesis.

Like other migraine types, HM can present with four stages: (1) a premonitory phase with non-headache symptoms; (2) an aura that includes motor symptoms; (3) the headache phase; and (4) a recovery or postdromic stage (Fig.1.2). Generally, the rst attack consists of a headache with aura but no hemiplegia. The number of attacks throughout life varies, reaching up to 0.4/year [11]. Triggering factors include physical and emotional stress and even pregnancy.

The total duration of all aura symptoms can vary from 10min to 7days, although the most typical duration is 60–120min [14, 15]. Each symptom typically lasts between 5 and 30min [1, 14, 15]. The classic sequence of aura presentation begins with visual, sensory, motor, aphasic, and basilar manifestations. There may be other types of aura with different combinations [1, 14].

Brainstem aura symptoms are reported in 60–73% of cases, with manifestations as diverse as decreased hearing, dizziness, tinnitus, a sensation of pressure and pain in the ear, loss of balance, vertigo, clumsiness in the hands, dropping of objects, dysarthria, diplopia, tongue stiffness, pharyngeal and tongue numbness, swallowing difculties, drop attacks, and decreased level of consciousness [1, 13–16].

The pain is of moderate to severe intensity and worsens with physical activity. It starts during or after the visual aura or, very rarely, before [14, 15]. Its duration var­ies from 4 to 72h, with some cases lasting from 5min to 5days [1, 14, 15]. Non­headache symptoms might occur during headache attacks and include nausea (84–94%), vomiting (58–80%), phonophobia (70–92%), photophobia (70–99%), fever (8–58%), and mental confusion and disorientation (36–81%). Other manifes­tations have been reported, including autonomic symptoms (e.g., nasal congestion, lacrimation), motion sickness, Raynaud’s syndrome, loss of consciousness, and sei­zures [17]. In the pediatric population, irritability, agitation, and drowsiness may occur [17]. More severe symptoms include visual hallucinations, meningismus, limb alienation, apraxia, hyperacusis, and torticollis [21].