Cortical Spreading Depression Mimicking Ischemic Stroke: A Case Report of Complex Hemiplegic Migraine with Reversible Cortical Magnetic Resonance Imaging Changes

Abstract

Introduction

Hemiplegic migraine (HM) is a rare subtype of migraine with aura characterized by transient motor weakness and focal neurological deficits that can closely resemble acute ischemic stroke. Cortical spreading depression, the underlying electrophysiological mechanism, produces transient neuronal and vascular changes that may lead to stroke-like imaging findings, creating diagnostic challenges in emergency settings.

Case Presentation

We describe a 66-year-old man with a long-standing history of migraine with aura who presented with acute left-sided hemiparesis, dysarthria, and visual disturbances. Initial computed tomography revealed subtle sulcal effacement without evidence of hemorrhage. Brain MRI demonstrated right hemispheric diffusion-weighted hyperintensities without corresponding apparent diffusion coefficient (ADC) reduction, suggesting transient cytotoxic edema rather than infarction. Electroencephalography showed right hemispheric slowing without epileptiform discharges, and cerebrospinal fluid analysis was unremarkable. The patient experienced gradual clinical improvement over 7 days, with mild residual fine motor deficits at discharge. Preventive therapy with flunarizine was initiated.

Conclusion

This case underscores the importance of recognizing HM as a stroke mimic. Integration of the clinical context with MRI findings – particularly the absence of ADC restriction – can help differentiate HM from acute ischemic stroke and guide appropriate clinical management. Early and accurate diagnosis, together with individualized prophylactic treatment, may help reduce recurrence and long-term morbidity.

Introduction

Migraine is a prevalent neurological disorder affecting approximately 15% of the population worldwide, characterized by episodic attacks of moderate to severe headache, often accompanied by nausea, photophobia, and phonophobia. In around one-third of patients, these headaches are preceded or accompanied by transient neurological symptoms known as aura, which most commonly involve visual phenomena but may also include sensory, language, or motor disturbances [1].

One rare but clinically significant variant is hemiplegic migraine (HM), a subtype of migraine with aura that presents with unilateral motor weakness. HM can be either familial (FHM) or sporadic (SHM), with the familial form linked to mutations in ion channel genes such as CACNA1A, ATP1A2, and SCN1A [2, 3]. These genetic mutations are believed to lower the threshold for cortical spreading depression (CSD), the electrophysiological mechanism thought to underlie the aura phase.

CSD is defined as a slowly propagating wave of neuronal and glial depolarization, followed by a period of suppressed neural activity, spreading across the cortex at a rate of 2–5 mm/min. It is associated with profound but transient changes in cortical excitability, cerebral blood flow, and metabolic demand [3]. Functional imaging studies and animal models have confirmed that CSD can result in regional hypoperfusion and transient cortical dysfunction, which can mimic the imaging and clinical features of acute ischemic stroke [4, 5].

Particularly in older patients without acute vascular risk factors or those with known migraine history, the presentation of HM may lead to diagnostic confusion and unnecessary administration of thrombolytic therapy. Diffusion-weighted MRI (DWI) may reveal cortical hyperintensities that are not accompanied by apparent diffusion coefficient (ADC) reduction – unlike in true infarcts, where ADC is typically decreased due to cytotoxic edema [3–5]. This distinction is critical for appropriate management.

The CARE Checklist has been completed by the authors for this case report and is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000551416).

Case Report

A 66-year-old male with a long-standing history of migraine with aura since adolescence, presented to the emergency department with acute left-sided hemiparesis, predominantly affecting the arm, accompanied by gait disturbance, dysarthria, and visual symptoms. As reported by the patient’s wife, the symptoms began suddenly upon awakening. The patient had experienced 3–4 migraine episodes annually, often accompanied by visual aura, and occasionally with motor symptoms suggestive of a hemiplegic component. This weakness had always been transient, typically lasting less than 6 h with gradual fading. However, in the current episode, the symptoms persisted for more than 24 h upon admission.

He had no regular migraine prophylaxis. His past imaging studies had been unremarkable. His father reportedly died of a stroke at age 63, though further details were unknown.

On admission, clinical examination revealed left-sided hemiparesis (4/5 strength), mild neglect, and visual field disturbance. Initial CT imaging showed subtle effacement of cortical sulci in the right hemisphere, but no acute hemorrhage or early ischemic changes (Fig. 1). Given the stroke-like presentation, he was admitted under the acute stroke protocol.

Fig. 1.

Non-contrast cranial CT scan on admission showing subtle effacement of cortical sulci in the right parietal region (arrow), suggestive of mild cortical swelling without evidence of acute infarction or hemorrhage.

Subsequent MRI imaging demonstrated focal cortical swelling and signal abnormalities in the right cerebral hemisphere, with diffusion-weighted imaging (DWI) hyperintensities without corresponding ADC reduction and only subtle, non-territorial FLAIR hyperintensity, suggesting CSD rather than acute infarction. Additional foci were observed in the left hippocampus and bilateral insulae (Fig. 2–5). Lumbar puncture was performed to exclude infectious or autoimmune causes, yielding normal CSF parameters. EEG showed focal slowing over the right hemisphere without epileptiform dis-charges. The diagnosis of epileptic seizure was considered but deemed unlikely.

Fig. 2.

Axial diffusion-weighted imaging (DWI) from MRI demonstrates focal cortical hyperintensities predominantly in the right posterior parietal lobe.

Fig. 5.

Axial FLAIR MRI shows subtle cortical hyperintensity and mild sulcal effacement without territorial infarction.

Fig. 3.

Axial diffusion-weighted imaging (DWI) confirms multifocal and asymmetric cortical DWI signal elevations in the bilateral insular cortices and left hippocampus. No corresponding ADC signal drop was observed (not shown), supporting a diagnosis of HM.

Fig. 4.

Corresponding ADC map shows no diffusion restriction, arguing against acute infarction.

By the sixth day, a follow-up MRI showed regression of the cortical signal changes (Fig. 6). His condition was attributed to a complex HM episode with CSD. He was initiated on flunarizine for migraine prophylaxis, and a follow-up MRI was scheduled.

Fig. 6.

Follow-up MRI (day 6) shows regression of the previously noted cortical DWI hyperintensities bilaterally, consistent with resolving CSD.

Neurologically, his deficits improved slowly after 7 days, with only mild fine motor impairment of the left hand persisting; other symptoms regressed completely. Due to persistent but improving motor deficits, the patient was transferred for geriatric rehabilitation. Application for a nursing care level was initiated. Depending on his functional recovery, neurological rehabilitation was also being considered. After 14 days, all symptoms had resolved. He was discharged in stable condition with outpatient neurologic follow-up arranged.

Discussion

This case underscores the clinical complexity of distinguishing HM from acute ischemic stroke, particularly in older adults presenting with focal neurological deficits. HM is a rare subtype of migraine with aura characterized by transient motor weakness, often accompanied by other aura symptoms such as visual disturbances, sensory changes, or aphasia [4, 6].

CSD, the electrophysiological phenomenon underlying migraine aura, involves a transient wave of neuronal depolarization followed by pro-longed cortical suppression. This depolarization wave propagates slowly across the cortex and is associated with regional alterations in cerebral blood flow and metabolism [7, 8]. In imaging, CSD may manifest as reversible cortical diffusion restriction without ADC reduction, which differentiates it from true ischemic lesions [6, 9].

According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), HM is defined by migraine attacks with fully reversible motor weakness accompanied by at least one additional aura symptom [1, 6]. In the present case, the patient fulfilled the diagnostic criteria for SHM, including recurrent attacks since adolescence, reversible unilateral motor weakness, visual aura symptoms, and complete clinical recovery. No first-degree relative with similar migraine attacks was known, supporting the diagnosis of SHM rather than FHM.

CSD itself propagates over minutes, typically at a rate of 2–5 mm/min; however, its clinical manifestations and imaging correlates may persist for hours to days [4, 5]. Importantly, unlike acute ischemic stroke, CSD does not result in sustained energy failure or irreversible cytotoxic edema. Neuronal membrane depolarization and transient ionic shifts occur without permanent disruption of cellular integrity. Consequently, ADC values typically remain normal or only minimally altered despite the presence of DWI hyperintensities [4–6]. This imaging pattern reflects transient metabolic dysfunction rather than infarction.

Our patient’s MRI findings – DWI hyperintensities without corresponding ADC restriction – are consistent with previous descriptions of CSD-related changes. This pattern has been increasingly recognized as an imaging biomarker for migraine aura, particularly in complex cases such as HM [3–6, 9]. Studies have shown that CSD can transiently disrupt neuronal ionic gradients, cause regional hypoperfusion, and result in transient cortical swelling – all without permanent infarction [10].

The clinical presentation of HM often overlaps significantly with stroke. Features such as hemiparesis, dysarthria, and neglect are traditionally associated with right hemispheric ischemia, and CT imaging in the acute phase may not provide sufficient discriminatory power. Consequently, MRI – including DWI and ADC sequences – plays a pivotal role in the differentiation. In HM, the presence of DWI changes in the absence of ADC reduction strongly favors a diagnosis of reversible cortical dysfunction due to CSD [7, 10].

Although CSD is a recognized mechanism in HM, the exact pathophysiological cascade remains under investigation. Genetic studies have identified mutations in ion channel genes such as CACNA1A, ATP1A2, and SCN1A in FHM, which increase cortical excitability and lower the threshold for CSD initiation [7, 8]. While our patient did not undergo genetic testing, the presence of recurrent aura with motor symptoms raises the possibility of an underlying genetic predisposition.

Electroencephalography in our case showed focal slowing without epileptiform discharges, further supporting a diagnosis of migraine rather than seizure. Additionally, lumbar puncture results were unremarkable, helping to rule out encephalitis or other inflammatory causes. These findings underscore the importance of a multimodal diagnostic approach in cases of stroke mimics.

From a management perspective, avoiding unnecessary thrombolysis in stroke mimics such as HM is crucial. At the same time, these patients may benefit from targeted migraine prophylaxis. Flunarizine, a calcium channel blocker, has been shown to reduce migraine frequency and severity, likely by stabilizing neuronal membranes and reducing CSD susceptibility [8, 10].

The decision to initiate flunarizine in this patient was made after careful consideration of potential risks and benefits. In older patients, flunarizine is associated with an increased risk of adverse effects, including weight gain, depressive symptoms, and drug-induced parkinsonism [11]. Given the patient’s age and planned geriatric rehabilitation, close clinical monitoring was recommended, with particular attention to mood, extrapyramidal symptoms, and functional mobility. Alternative prophylactic options were discussed, and the indication for continued flunarizine therapy was planned to be regularly reassessed during follow-up.

This case adds to the growing body of literature supporting CSD as the physiological correlate of migraine aura and an important consideration in the differential diagnosis of acute neurological syndromes. Recent intracranial recordings in humans have provided direct electrophysiological evidence of CSD during aura episodes, underscoring its clinical relevance.

Given the patient’s advanced age and family history of stroke, an extensive differential diagnostic evaluation was performed. Acute ischemic stroke was considered unlikely owing to the absence of ADC restriction, non-territorial and reversible MRI abnormalities, and complete radiological regression on follow-up imaging. Epileptic, structural, infectious, inflammatory, and vascular causes were excluded by EEG, cerebrospinal fluid analysis, and imaging studies, supporting HM with CSD as the most plausible diagnosis.

Characteristic features of this case include multifocal and asymmetric cortical DWI hyperintensities without corresponding ADC reduction, subtle non-territorial FLAIR changes, focal EEG slowing, and complete radiological reversibility. The patient’s advanced age further highlights the diagnostic challenge of HM as a stroke mimic in individuals with increased vascular risk.

Conclusion

This case highlights the clinical significance of cortical spreading depolarization (CSD) as a physiological correlate of migraine aura and its ability to mimic acute neurological events such as ischemic stroke. Emerging evidence from human intracranial recordings supports the occurrence of CSD during aura episodes, reinforcing its diagnostic relevance. Recognition of CSD-related phenomena is particularly important in patients with a history of migraine to avoid misdiagnosis and inappropriate acute stroke management. Advanced neuroimaging, especially DWI and ADC mapping, plays a pivotal role in distinguishing CSD from true cerebral infarction. Increased awareness of HM and its characteristic clinical and radiological features may improve diagnostic accuracy and optimize patient management.

Patient Perspective

The patient found the sudden left-sided weakness and visual disturbances frightening, especially given his family history of stroke. He was relieved that imaging confirmed a HM rather than a stroke. He appreciated the treatment plan, including flunarizine prophylaxis and follow-up care. Recovery was gradual, but he felt supported and better prepared to recognize and respond to future migraine episodes.

Statement of Ethics

According to institutional and national regulations, ethics approval was not required for single-patient case reports. Written informed consent for publication of this case report and the accompanying images was obtained from the patient.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This research received no specific grant or external financial support from any funding agency in the public, commercial, or not-for-profit sectors.

Author Contributions

Ali Hammed: conceptualization; case management and data curation; drafting of the manuscript; figure preparation; revision of the final version. Salah Hammed: literature review; drafting sections of Introduction/Discussion; verification of clinical data; critical revision for important intellectual content. Thomas Stein: radiological review and interpretation; selection and annotation of imaging; methods and Results revisions. Ulrich Niemöller: clinical supervision; contribution to case timeline and inpatient course; review of imaging-clinical correlation; manuscript editing. Marco Meyer: data verification; proofreading; references checking; final approval. Christian Tanislav: senior supervision; conception and design; critical revision of the manuscript for important intellectual content; final approval. Christian Tanislav accepts full responsibility for the integrity of the work, including the accuracy of the data and analysis.

Funding Statement

This research received no specific grant or external financial support from any funding agency in the public, commercial, or not-for-profit sectors.

Data Availability Statement

De-identified clinical data and imaging supporting this case are not publicly available due to patient privacy and institutional restrictions but can be made available from the corresponding author upon reasonable request and subject to data-sharing agreements.