The diagnostic role for susceptibility-weighted MRI during sporadic hemiplegic migraine

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1 Brief Report The diagnostic role for susceptibility-weighted MRI during sporadic hemiplegic migraine Cephalalgia 33(15) ! International Headache Society 2013 Reprints and permissions: sagepub.co.uk/journalspermissions.nav DOI: / cep.sagepub.com Erin M Fedak 1, Nicholas A Zumberge 2 and Geoffrey L Heyer 1 Abstract Background: Hemiplegic migraine is a rare form of migraine with aura that includes motor weakness. Diagnosis during the first episode can be difficult to make and costly, especially with the sporadic form. Cases: Our study evaluates the ictal magnetic resonance imaging (MRI) features of four sequential pediatric patients during a first-time, sporadic hemiplegic migraine. Susceptibility-weighted imaging (SWI) revealed cerebral venous prominence and increased magnetic susceptibility affecting brain regions that corresponded with each patient s neurologic deficits. Repeat MRI (performed in three patients) following migraine recovery demonstrated resolution of all susceptibility abnormalities. Conclusion: When combined with conventional MRI sequences, SWI has diagnostic value in the acute setting of motor weakness and with clinical features consistent with hemiplegic migraine. The sequence may help to further characterize ictal cerebral blood flow changes during the hemiplegic migraine aura. Keywords Hemiplegic migraine, pediatric, magnetic resonance imaging, susceptibility-weighted imaging Date received: 5 January 2013; revised: 9 March 2013; 11 April 2013; accepted: 27 April 2013 Introduction Hemiplegic migraine is a rare subtype of migraine with aura that includes motor weakness (1). The attacks of sporadic hemiplegic migraine (SHM) have identical clinical characteristics as the familial type of hemiplegic migraine (FHM), but patients lack the family history of first- or second-degree relatives affected by similar motor auras (2). The sporadic and familial forms occur rarely with an equal prevalence of 0.01% found in a Danish population of 5.2 million people (3). The first attack of SHM or FHM warrants a thorough clinical evaluation of the other potential causes of abrupt-onset neurologic deficits and headache. It is a diagnosis of exclusion. This remains true regardless of family history. Several neuroimaging studies have characterized alterations of cerebral blood flow during migraine with motor aura using various imaging modalities including computed tomography (CT) perfusion, perfusion-weighted magnetic resonance imaging (MRI), proton magnetic resonance spectroscopy, single-photon emission computed tomography (SPECT), and xenon isotope studies during provocation with carotid arteriography (4 13). While perfusion studies may be readily available at adult stroke centers, smaller hospitals and dedicated pediatric centers may not have acute stroke protocols in place. A non-contrast MRI sequence that is relatively brief, easily interpretable, has positive findings during the hemiplegic aura, and normalization after symptoms resolve would add tremendous diagnostic value to the routine MRI during the acute presentation of SHM weakness. We describe the ictal susceptibility-weighted imaging (SWI) MRI features that correspond with the clinical presentations of four pediatric patients with SHM and the post-ictal resolution of these SWI changes (three patients). 1 Division of Pediatric Neurology, Nationwide Children s Hospital, Columbus, OH, USA 2 Department of Radiology, Nationwide Children s Hospital, Columbus, OH, USA Corresponding author: Geoffrey L Heyer, Departments of Pediatrics and Neurology, Nationwide Children s Hospital, 700 Children s Dr., ED-5, Columbus, OH 43205, USA. geoffrey.heyer@nationwidechildrens.org

2 Fedak et al Figure 1. SWI during acute motor aura. Panel (a) (Patient 1) and panel (b) (Patient 2) demonstrate prominence of the cerebral veins and increased susceptibility affecting the right and left cerebral hemispheres, respectively. Patient 2 had normalization of all SWI changes on repeat MRI (not shown because of poor quality from interval placement of dental braces). MRI (panel (a)) performed using 3 T magnet (TE 26 ms/tr 44 ms/flip angle 15 degrees/slice thickness 2.2 mm). MRI (panel (b)) performed using 1.5 T magnet (TE 48 ms/ TR 76 ms/flip angle 15 degrees/slice thickness 3 mm). SWI: Susceptibility-weighted imaging; MRI: magnetic resonance imaging; TE: echo time; TR: repetition time. Subjects All subjects presented to Nationwide Children s Hospital with SHM between June 2011 and April This series includes all hemiplegic migraine patients imaged acutely during the study period. Brain MRI with SWI (GE Healthcare, Waukesha, WI) was performed during the early phase of motor aura. Aside from SWI, all imaging sequences were normal without signs of restricted diffusion, hemorrhage or other causes of acute paresis. Acquisition times for all SWI sequences were 4 minutes. Our case descriptions focus on the clinical signs and symptoms and the ictal and interictal SWI findings at the initial SHM presentation. Data regarding laboratory investigations and the results of additional neuroimaging are included below where pertinent. In all cases MRI was obtained prior to migraine treatment. This study was approved by the Institutional Review Board at Nationwide Children s Hospital, Columbus, Ohio, USA. Case 1 A 14-year-old girl presented with new-onset of slurred speech and left arm, face, and leg weakness and numbness. The episode began with tingling in the neck, followed by numbness of the left shoulder and upper arm. She had a past medical history of headaches consistent with migraine without aura and a family history of paternal migraines without aura or weakness. She arrived at the emergency department approximately one hour after symptom onset. Upon arrival, she developed a bifrontal headache with associated photophobia and osmophobia. The head pain was described as different in both quality and intensity compared to prior headaches. She was alert and cooperative during the neurologic exam, which revealed dysarthric speech, normal language, left facial droop, decreased left arm and leg strength (rated 3/5 4/5), and diminished leftside sensation. A brain MRI (3 Tesla) was performed about three hours and thirty minutes after symptom onset. SWI revealed prominence of the right cerebral cortical veins when compared to the left hemisphere (Figure 1(a)). Her headache and neurologic deficits began to improve about eight hours after onset, and all symptoms resolved by 24 hours. She has had a single repeat attack since her initial hospital discharge. Repeat brain MRI has not been performed. Case 2 A 10-year-old girl with a history of migraine headaches without aura presented to the emergency department with headache, right facial weakness, and difficulty forming words. She initially developed a left frontal headache that caused her to lie down and take a nap. She awoke with headache, weakness, and language difficulties. Photophobia, nausea, and vomiting followed. On examination in the emergency department, she was

3 1260 Cephalalgia 33(15) somnolent with some confusion. She had difficulty naming objects, repeating phrases, and following simple commands, and she had right-sided facial droop. An MRI (1.5 Tesla) was performed while symptomatic, six hours after symptom onset. SWI demonstrated an asymmetric prominence of the cortical veins in the left cerebral hemisphere (Figure 1(b)). She developed a low-grade fever during hospital admission that quickly resolved. The analysis of cerebrospinal fluid from lumbar puncture was normal. She had a repeat brain MRI (1.5 Tesla) four months later for a different clinical indication. She did not have headache or weakness at that time, and the SWI changes had resolved. However, repeat imaging is not included here because the interval placement of dental braces caused substantial susceptibility artifact and poor image quality. Case 3 A previously healthy 8-year-old girl presented to an outside hospital emergency department with right arm, face, and leg weakness, slurred speech, and blurry vision. Her attack began with difficulty holding a utensil with her right hand. This was followed by dizziness and a severe frontal headache. After onset of weakness her mother reported that at least twice the child had bumped into a wall while walking. She was transferred to our center for stroke evaluation. Upon transfer she developed nausea with two episodes of vomiting. She was alert but somnolent on exam. Her neurologic findings included difficulty naming objects, a presumed right-side visual field defect, right facial weakness with drooling, dysarthria, and weakness of the right hand and arm. MRI (3 Tesla), performed approximately four hours after symptom onset, revealed prominence of the left cerebral vasculature on SWI (Figure 2(a)). SWI changes resolved (Figure 2(b)) with repeat MRI (3 Tesla) the following morning after symptom resolution. The child denied any prior headaches with migrainous features. Her mother has a history of migraine with aura but denies prior weakness related to aura or headache. Case 4 A 12-year-old girl with a medical history of attentiondeficit disorder and mild headaches without aura developed word-finding difficulties. She presented to an outside hospital emergency department and was immediately transferred to our center for stroke evaluation. Her examination revealed aphasia, a presumed right visual field defect, and a right arm pronator drift. A brain MRI (1.5 Tesla) was performed 4.5 hours after symptom onset. The SWI sequence revealed asymmetric prominence of the left cerebral vasculature (Figure 1(c)). Following MRI the patient developed headache with nausea and vomiting. All symptoms resolved by the following morning. Given the prolonged interval between aura onset and headache onset, several additional clinical studies were performed. Among these, cerebral spinal fluid assessment (performed after MRI) and electroencephalogram (performed the following morning) were normal. She had a repeat MRI (1.5 Tesla) after symptom resolution the next day that revealed normalization of all SWI changes (Figure 1(d)). Her mother has a history of migraine associated with lip numbness but no weakness. Her sister has a history of migraine without aura. She has developed migraine with aura (but without motor aura) since this presentation. Discussion We describe four consecutive pediatric cases of SHM with abnormalities on SWI during their migrainous aura within three to six hours from symptom onset. Repeat imaging performed on three of the subjects following symptom recovery revealed resolution of all ictal SWI changes. SWI provides information about any tissue with magnetic susceptibility that differs from neighboring structures (14). Iron- and calcium-rich tissues have increased magnetic susceptibility. The various forms of brain iron include deoxygenated blood, hemosiderin, and ferritin. SWI generates a source of contrast from the relative differences in tissue-iron content. This contrast is different from that of spin density, T1, T2, and T2*. Our center began using SWI in all cases of suspected stroke or hemorrhage. The sequence has gradually become routine in all MRIs. In each of our reported patients the ictal SWI showed asymmetrical prominence of the cerebral veins during symptoms of SHM aura. Altinok and colleagues report an 11-year-old girl with FHM and similar SWI changes with corresponding diminished perfusion on perfusion-weighted imaging (PWI) (5). She had a small region of restricted diffusion in the parietal lobe of the affected cerebral hemisphere. All imaging abnormalities resolved on a follow-up MRI performed three days later. The authors suggest that impaired regional blood flow during the attack led to an uncoupling of oxygen supply and demand in the hypoperfused brain, leading to an increase in venous deoxyhemoglobin and consequent changes in venous magnetic susceptibility. The SWI changes in our cases of SHM match this report of a child with FHM. Two additional cases are reported by Karaarslan et al. (4). The first, a 37-year-old man, had migraine with a left visual-field defect and right arm and face numbness.

4 Fedak et al Figure 2. Acute SWI changes resolve when symptoms improve. Panels (a) and (b) (Patient 3) show SWI changes affecting the left cerebral vasculature (panel A) and resolution of changes after symptomatic improvement (panel B). Panels (c) and (d) (Patient 4) demonstrate similar acute SWI changes (panel (c)) affecting the left cerebral veins and resolution (panel (d)) on repeat MRI. MRI (panels (a) and (b)) performed using 3 T magnet (TE 26 ms/tr 44 ms/flip angle 15 degrees/slice thickness 2.2 mm). MRI (panels (c) and (d)) performed using 1.5 T magnet (TE 48 ms/tr 76 ms/flip angle 15 degrees/ slice thickness 3 mm). SWI: Susceptibility-weighted imaging; MRI: magnetic resonance imaging; TE: echo time; TR: repetition time. Weakness was not described. Their second case involved a 9-year-old boy with headache, right arm numbness, dysarthria, and right facial weakness. Both patients had asymmetric prominence of the cerebral veins on SWI and impaired perfusion on PWI (affecting the right and left cerebral hemispheres, respectively). As weakness was not detected in their first subject, motor weakness during migraine attacks may not be necessary to induce SWI changes. The pathogenesis of migraine aura follows Lea o s original description of cortical spreading depression (15). The typical migraine aura is characterized by diminished cerebral blood flow beginning posteriorly and spreading anteriorly (16 20). Less is known about the alterations in blood flow during hemiplegic migraine. Neuroimaging studies performed during the early phase of the motor aura have demonstrated regional hypoperfusion in most cases (4 8). An exception is reported by Lindahl and colleagues, who describe a 21-year-old woman with FHM (21). Six hours following the onset of headache, language disturbance, and right-sided arm weakness, her ictal perfusion-weighted MRI showed hyperperfusion of the left cerebral hemisphere. Other cerebral blood flow studies have demonstrated hyperperfusion occurring in the latter stages of the aura (10 13,22). In these reports subjects had

5 1262 Cephalalgia 33(15) prolonged periods of motor weakness with neuroimaging performed 48 hours or later following symptom onset. Cerebral edema coincided with hyperperfusion in some subjects (10,12,13,22). Our patients had distinct changes in the appearance of cerebral veins on SWI within six hours of symptom onset, presumably related to a buildup of venous deoxyhemoglobin and an increase in magnetic susceptibility. The link between similar SWI changes and diminished perfusion described by Altinok et al. (5) and Karaarslan et al. (4) supports the model of early hypoperfusion as the cause of susceptibility changes. In our four SHM cases the SWI changes occurred in the cerebral hemisphere that corresponds with each patient s respective neurologic deficits. Two of our subjects had repeat MR imaging one day following hospital admission, and a third subject had repeat imaging four months later. Each patient was symptom free when repeat imaging was performed, and the resolution of symptoms corresponded with normalization of the susceptibility defect. SHM is a diagnosis of exclusion during the first attack. We propose that the SWI sequence has diagnostic value in the acute setting of hemiplegic aura, particularly when other MRI sequences are normal. However, we do not yet know the diagnostic sensitivity and specificity of the sequence as it relates to SHM or FHM. Future studies should address the possibility of SWI changes in migraine aura without motor weakness. Serial SWI during the motor aura would help to determine at what point the susceptibility defect normalizes. Conclusion When combined with conventional MRI sequences, SWI has diagnostic value in the acute setting of motor weakness and with clinical features consistent with hemiplegic migraine. The MRI sequence is relatively brief (4 minutes), easily interpretable, adds no additional cost, and does not require contrast. Study of susceptibility changes during the motor aura will help to further characterize alterations in cerebral blood flow during hemiplegic attacks. Clinical implications. Sporadic hemiplegic migraine can be difficult and costly to diagnose, particularly during the first attack.. Susceptibility-weighted imaging (SWI) can show cerebrovascular changes during the acute phase of sporadic hemiplegic migraine that correspond to clinical impairments.. SWI abnormalities resolve when symptoms improve.. SWI is a relatively brief, non-contrast MRI sequence that has diagnostic value during the acute phase of hemiplegic migraine. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of interest None declared. References 1. Black DF. Sporadic and familial hemiplegic migraine: Diagnosis and treatment. Semin Neurol 2006; 26: The International Classification of Headache Disorders. 2nd ed. Cephalalgia 2004; 24 (Suppl 1): Lykke TL, Kirchmann EM, Faerch RS, et al. An epidemiological survey of hemiplegic migraine. Cephalalgia 2002; 22: Karaarslan E, Ulus S and Ku rtu ncu M. Susceptibilityweighted imaging in migraine with aura. AJNR Am J Neuroradiol 2011; 32: E5 E7. 5. Altinok D, Agarwal A, Ascadi G, et al. Pediatric hemiplegic migraine: Susceptibility weighted and MR perfusion imaging abnormality. Pediatr Radiol 2010; 40: Eom TH, Bin JH, Kim YH, et al. A pediatric sporadic hemiplegic migraine case with perfusion abnormality in perfusion MRI and Diamox 99mTc-HMPAO SPECT. Neurol Sci 2013; 34: Hansen JM, Schytz HW, Larsen VA, et al. Hemiplegic migraine aura begins with cerebral hypoperfusion: Imaging in the acute phase. Headache 2011; 51: Friberg L, Olsen TS, Roland PE, et al. Focal ischaemia caused by instability of cerebrovascular tone during attacks of hemiplegic migraine. A regional cerebral blood flow study. Brain 1987; 110: Toldo I, Cecchin D, Sartori S, et al. Multimodal neuroimaging in a child with sporadic hemiplegic migraine: A contribution to understanding pathogenesis. Cephalalgia 2011; 31: Hsu DA, Stafstrom CE, Rowley HA, et al. Hemiplegic migraine: Hyperperfusion and abortive therapy with intravenous verapamil. Brain Dev 2008; 30: Masuzaki M, Utsunomiya H, Yasumoto S, et al. A case of hemiplegic migraine in childhood: Transient unilateral hyperperfusion revealed by perfusion MR imaging and MR angiography. AJNR Am J Neuroradiol 2001; 22:

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