Dysmetropsia and Cotard's syndrome due to migrainous infarction – or not?

Abstract

Introduction

Migrainous infarction accounts for 12.8% of ischemic strokes of unusual etiology.

Case report

A 59-year-old woman with longstanding migraine with aura experienced what appeared to be migrainous infarction characterized by dysmetropsia and transient Cotard’s syndrome. Imaging demonstrated right temporal-parietal-occipital changes with apparent cortical laminar necrosis.

Conclusion

The spectrum of the pathophysiology of migrainous infarction has not been established; however, cortical spreading depression may explain the appearance of imaging findings that do not obey a vascular territory.

Introduction

Migrainous infarction is a rare condition that accounts for only 0.8% of first-ever ischemic stroke; however, 12.8% of ischemic strokes of unusual etiology are attributed to migraine (1). Migrainous infarction is defined by strict criteria developed by the International Headache Society (2). Diagnosis of migrainous infarction requires persistence of at least one typical aura symptom for more than 60 minutes in a patient with established migraine with aura, radiographic evidence of infarction, and exclusion of other stroke etiologies. The pathophysiology of migrainous infarction has not been established; however, cortical spreading depression (CSD) may explain infarction that does not obey a vascular territory (3). We present a case that appeared to have migrainous infarction, as suggested by the presence of apparent cortical laminar necrosis (CLN) not obeying a vascular territory, and we discuss potential etiology of this phenomenon. Patient consent was obtained for this report in accordance with Capital Health research ethics board policy. The patient provided written consent for use of artwork.

Case report

A 59-year-old right-hand dominant woman was diagnosed with what appeared to be migrainous infarction following a typical migraine with aura. Migraines began at approximately 40 years of age with subsequent frequency of approximately one headache per month. Migraines were side-locked with a stabbing pain located in the right frontal region. Photophobia and phonophobia always accompanied headache and headaches persisted for 24 to 48 hours. Migraine headache was always preceded by aura. For over 15 years, she experienced an approximately 15-minute fortification scotoma with onset of headache during visual aura resolution. Two years prior to the migrainous infarction, aura changed such that it consisted of an approximately 10-minute fortification scotoma followed by an approximately 10-minute episode of left leg numbness with subsequent onset of headache. Two months prior to migrainous infarction, typical visual aura followed by left leg sensory phenomena were both accompanied by receptive and expressive dysphasia in an aura that evolved over approximately 30 minutes.

The episode in question began with an approximately 15-minute fortification scotoma, which was followed by an approximately 15-minute episode of numbness that spread from the left hip into the left leg. Visual and sensory phenomena were accompanied by receptive and expressive language difficulty that persisted for several hours. A throbbing right frontal headache associated with photophobia and phonophobia developed following resolution of visual and sensory symptoms. Despite zolmitriptan at headache onset, the headache intensified over several hours with development of visual illusions within approximately 2 hours of headache onset. Over the next 2 weeks, she experienced a persistent visual perceptual disturbance (Figure 1), and an approximately 60-minute episode whereby she had the delusion of being dead (transient Cotard's syndrome). Examination was remarkable for left homonymous hemifield visual distortion and decreased left-hand 2-point discrimination. Imaging suggested right temporal-parietal-occipital cortical infarction (Figure 2).

Figure 1.

Patient artwork depicting her experience of dysmetropsia. She perceived people that looked like figures ‘in a fun house’, appearing short and wide or tall and slender with disfigured facial features (eyes, ears) that appeared ‘alien’. In addition, articles of clothing (shirts, shoes) were magnified.

Figure 2.

MRI 2 weeks after symptom onset suggested restricted diffusion involving only the cortical grey matter in the right temporal-parietal-occipital lobe with gyriform gadolinium enhancement on T1 (a, b), restricted diffusion on diffusion weighted imaging (c), corresponding decreased ADC values (d), T2 hyperintensity on FLAIR (e), and isointense T1 (f).

Vascular risk factors included hypertension and dyslipidemia. Past medical history was significant for obstructive sleep apnea, melanoma excised 7 years prior from the right shoulder, and right breast lumpectomy for ductal carcinoma in situ approximately 1 month prior to apparent migrainous infarction. MR angiogram demonstrated normal carotid arteries, minor focal stenosis of the right vertebral artery, a hypoplastic right posterior communicating artery, and a hypoplastic anterior communicating artery. Transthoracic echo did not demonstrate a cardiac source of emboli. EEG did not demonstrate epileptiform activity. Ultimately, diagnosis was felt to be migrainous infarction. Aspirin was initiated and vascular risk factors (hypertension and dyslipidemia) were addressed. Visual illusions gradually improved. She was not started on medication for migraine prophylaxis and experienced only one migraine over the next year. Migraine aura consisted of left hemibody numbness and expressive language difficulty, which persisted for ∼30 minutes followed by headache onset.

Remarkably, a follow-up MR scan 18 months later showed no evidence of prior stroke.

Discussion

Dysmetropsia and Cotard’s syndrome are higher cortical function disorders manifested in this case of what appeared to be migrainous infarction. Cotard’s syndrome, an extreme form of nihilism, has only been reported in one other migraine case (4). Interestingly, higher cortical dysfunction during migraine aura is associated with longer aura duration (5). Is there an association between prolonged migraine aura and migrainous infarction, or was this truly a migrainous infarction or something else?

Migraine with aura is associated with a twofold increase in overall risk of ischemic stroke (6), and may confer an even greater risk to women older than 45 years (7). The pathophysiological correlate of aura is CSD, a wave of neuronal and glial depolarization that propagates at approximately 3 mm/min without respecting vascular territories (8). Depolarization of adjacent tissue occurs by raised extracellular K⁺ resulting from massive intracellular K⁺ efflux.

CSD is triggered by transient microvascular occlusion insufficient to cause tissue damage on histological analysis (9). Patent foramen ovale, a right-to-left cardiac shunt that increases risk of venous microemboli, may be twice as prevalent among patients with migraine (10). In addition, subclinical infarct-like posterior circulation lesions are significantly more prevalent in migraine with aura (8.1%) than in migraine without aura (3.0%) or controls (2.9%) (11). If microemboli can initiate aura, then migraine with aura may exist on a continuum with ischemic stroke (8).

CSD is associated with a triphasic vasomotor response, evolving from vasoconstriction to hyperemia to a prolonged period of oligemia (3). During migraine with visual aura, perfusion MRI demonstrates reduced cerebral blood flow and volume in the affected occipital lobe (12). Among posterior circulation infarct-like lesions in migraine with aura patients, ∼90% of infratentorial lesions are located in border zone regions vulnerable to hypoperfusion (11). Perhaps, oligemia associated with migraine aura occasionally results in migrainous infarction.

Migrainous infarction has previously been shown to assume the appearance of CLN on MRI (13–15); however, it is important to note that proven CLN is a pathology diagnosis (13). This case demonstrates transient but no permanent imaging findings. Migratory cortical edema associated with transient diffusion restriction has been observed in persistent aura without infarction (16). This phenomenon is theorized to be secondary to repetitive depolarizing waves within a defined region. Recurrent spreading depression-like depolarizing waves are known to occur in the region of ischemic penumbra with propagation into normal tissue (3). Recurrent focal CSD may account for persistent aura without infarction and have the potential to progress to migrainous infarction.

Cortical enhancement on MRI similar to this case occurred in migrainous infarction associated with extensive cortical laminar necrosis (13). Cortical enhancement in migrainous infarction is secondary to decreased integrity of the blood brain barrier, possibly caused by both hypoperfusion and hyperperfusion in the context of CSD. Similar reversible cortical enhancement has been observed in status epilepticus (17). Interestingly, CSD is associated with enhanced cerebral excitability and epilepsy (8). Susceptibility to CSD, experienced by the patient as migraine with aura, is likely to be multifactorial with vascular, as well as, other modulators.

Ultimately, this case of migrainous infarction or a metabolic process resulting in CLN-like changes illustrates that CSD is a plausible explanation for imaging findings that do not localize to a vascular territory.

Clinical implications

Migrainous infarction or a metabolic process producing CLN-like changes may present with higher cortical dysfunction.

Migraine with aura may exist on a spectrum with ischemic stroke.

Cortical spreading depression, the pathophysiological correlate of migraine aura, may cause remarkable and sometimes reversible neurologic imaging findings that do not localize to a vascular territory.