Brain & Development 26 (2004) 535–538 www.elsevier.com/locate/braindev Case report MR imaging and 1H-MR spectroscopy in a case of cerebral infarction with transient cerebral arteriopathy Atsushi Imamuraa,*, Naoki Matsuoa, Masako Arikia, Hiroko Horikoshia, Tatsuaki Hattorib a Department of Pediatrics, Gifu Prefectural Gifu Hospital, 4-6-1, Noishiki, Gifu 500-8717, Japan b Department of Neurosurgery, Gifu Prefectural Gifu Hospital, Gifu 500-8717, Japan Received 2 September 2003; received in revised form 6 February 2004; accepted 6 February 2004 Abstract A case of cerebral infarction with transient cerebral arteriopathy in a 12-year-old female is described. The child showed with an acute onset of left hemiplegia, central facial palsy and aphasia. She was diagnosed with right internal carotid artery obstruction with no predisposing factors for cerebral infarction. A serial MR image and MR spectroscopy of the brain was performed. MR angiography revealed reversible vascular changes in the right middle cerebral artery after several months. The ratio of choline/creatine was elevated and that of Nacetylaspartate (NAA)/creatine was depressed in the cerebral lesion, however, they were normalized during the remission phase with long echo time-MR spectroscopy. The elevation of the lactate peak was clarified with short echo time-MR spectroscopy. The longitudinal follow up using MR angiography, and MR spectroscopy with long and short echo time was useful for the evaluation of reversible vascular change with cerebral infarction in children. q 2004 Elsevier B.V. All rights reserved. Keywords: Cerebral infarction; Transient cerebral arteriopathy; MR image; MR spectroscopy; Choline; Lactate 1. Introduction 2. Case report Ischemic cerebral infarction is rare in childhood. Although the risk factors for childhood stroke include multiple diseases, such as congenital heart disorders, cerebral trauma, infection, sickle cell anemia, and metabolic disorders, no risk factors can be found in 25– 50% affected children [1]. A recent study revealed that a high proportion of cerebrovascular disease includes idiopathic cerebral infarction, termed transient cerebral arteriopathy [2]. We present a case of cerebral infarction caused by dissection of the right internal carotid artery of unknown etiology. Serial MR angiography and MR spectroscopy showed reversible vascular changes in the arterial lesion. We discuss the evaluation of neuronal ischemic changes with this patient using neuroradiological methods. A 12-year-old girl suddenly demonstrated right occipital pain after running at school. She was admitted to the Gifu Prefectural Hospital because of prolonged headache, muscle weakness developing in her left upper and lower extremities, and presumed global aphasia. She had no significant medical history, such as congenital heart disease, epilepsy, or migraines. At the time of the event, she had no preceding febrile illnesses, and her family history of acute stroke was unremarkable. Cranial computed tomography (CT) revealed no marked change, however, hypo-intense and hyperintense lesions in the right middle cerebral artery area including lacunar areas were shown with T1-weighted and T2-weighted MR images, respectively. MR angiography indicated an obstruction in the right terminal tract of the carotid siphon and the horizontal portion of the right middle cerebral artery. Cerebral angiography showed a tail-like narrowing lesion in the right internal carotid artery. The left MR angiography and cerebral angiography were normal (Fig. 1). Laboratory findings at admission were normal, including coagulations test, including prothrombin time, activated partial thromboplastin time, fibrinogen, * Corresponding author. Tel.: þ 81-58-246-1111; fax: þ81-58-248-3805. E-mail address: aimamura30@hotmail.com (A. Imamura). 0387-7604/$ - see front matter q 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.braindev.2004.02.006 536 A. Imamura et al. / Brain & Development 26 (2004) 535–538 Fig. 1. Cerebral angiography (A: right carotid arteriography, B: left carotid arteriography) of the patient with right internal carotid artery obstruction. The arrow shows a ‘tail-like’ narrowing, a characteristic image for transient cerebral arteriopathy, of the right internal carotid artery. Three-dimensional-time of flight MR angiography (TR ¼ 27 ms; TE ¼ 3.2 ms, flip angle ¼ 208 (C, D)) and MRI (TR ¼ 3000 ms; TE ¼ 105 ms for T2-weighted (E, F) images) of the patient. Upper panels (C,E) and lower panels (D, F) represent images obtained at 2 and 6 months after the stroke, respectively. MR angiography revealed reversible vascular change of the right internal carotid artery at 6 months after the stroke. antithrombin III, and protein C and S levels. Serum amino acid analysis including homocysteine, plasma lactate and pyruvate levels were also normal. Therefore, the patient was administered low dose aspirin (3 mg/kg/day) to prevent stroke recurrence, and a rehabilitation program was initiated. One month later, MR angiography showed spontaneous regression, however, split dose 131I-IMP single photon emission CT (SPECT) revealed misery perfusion in the right middle cerebral artery lesion. Serial MR angiography was performed at 2, 4, 6, and 8 months after the stroke, and vascular narrowing was no longer detected (Fig. 1). Electrocardiography and echocardiography were normal. Localization of a 15 £ 15 £ 15 mm3 region of interest (ROI) was achieved using long and short TE (250 and 30 ms, respectively) point-resolved spectroscopy sequences. Proton MR spectra from different ROIs were acquired within measuring times of 5 min each (TR 2000 ms, 128 accumulations). MR spectroscopy was performed in two stages, 2 and 6 months after the stroke attack. MR spectroscopy revealed a low NAA/creatine (Cr) ratio (1.35; normal at 5– 15 years, 1.80 ^ 0.17) and a high choline (Cho)/Cr ratio (2.07; normal at 5 – 15 years, 0.89 ^ 0.12) [3,4] with long TE in the ishemic lesion at the earlier stage (Fig. 2). The ratios of NAA/Cr and Cho/Cr were nearly normalized at a later stage, 1.76 and 1.37, respectively. The NAA/Cho ratio improved from 0.65 to 1.28 after 4 months of treatment (Fig. 3). The lactate peak was elevated in the lesion with short TE, however, it was unclear with long TE MR spectroscopy in both stages (Figs. 2 and 3). Her headache and aphasia improved within a few days, however, the mild left hemiplegia remained. 3. Discussion Ishemic cerebral infarction is rare in childhood. In a previous study, the frequency, excluding children with sickle cell disease, was less than 1 in 100,000. Although the etiology was unknown in the present patient, arteriopathic stroke is the most common cerebral infarction in children [1,5]. Cerebral arteriopathy is characterized by the following two characteristics: first, subcortical infarcts, such as basal ganglia and internal capsule, associated with lesions of the cerebral arterial wall are mostly located in the initial parts of the basal arteries of the carotid system, and second, clinical and angiographic follow up should demonstrate a regression or arrest of the evolution of the arteriopathy [2,5]. In the present patient, a tail-like narrowing lesion in the proximal portion of the right internal carotid artery without string-bead signs, indicating fibromuscular dysplasia, was revealed in the early stages of the stroke by a cerebral angiogram [2,6], and reversible vascular changes were shown with serial MR angiography and SPECT. A. Imamura et al. / Brain & Development 26 (2004) 535–538 537 Fig. 2. Proton MR spectroscopy with short TE (30 ms: A, B) and long TE (250 ms: C, D) localized on the bilateral corpus striatum at 2 months after the stroke. That of the right lesion (solid square: A, C), which revealed T2 elongation on MRI, showed a peak lactate level at 1.3 ppm of the chemical shift with short TE, and increased Cho/Cr (2.07) and decreased NAA/Cr (1.35) with long TE. That of the left (dotted square: B, D) showed normal Cho/Cr (1.07) and NAA/Cr (2.39) ratios. Fig. 3. Proton MR spectroscopy with short TE (30 ms: A, B) and long TE (250 ms: C, D) localized on the bilateral corpus striatum 6 months after the stroke. That of the right lesion (solid square: A, C) also showed a lactate peak with short TE, however, the ratios of Cho/Cr and NAA/Cr improved to 1.37 and 1.76, respectively. That of the left (dotted square: B, D) indicated Cho/Cr and NAA/Cr as 1.31 and 2.69, respectively. 538 A. Imamura et al. / Brain & Development 26 (2004) 535–538 Inflammatry episodes, such as varicella zoster infection, were not shown. These findings suggest that the stroke may have been caused by transient cerebral arteriopathy of unknown origin as described by Chabrier et al. [2,5]. In the MR spectroscopy with long TE, low NAA/Cr and high Cho/Cr ratios were shown in the early stages after the stroke. NAA is located almost exclusively in neurons and axons, therefore, NAA is reduced in ischemic neuronal processes. NAA is degraded by enzymes within the injured neurons in the first few days or hours after infarction. Cho appears to contain contributions from phosphorylcholine and glycerophosphorylcholine, which are precursors to the cell membrane and breakdown products of the cell membrane, respectively. Therefore, an increased Cho signal may reflect membrane degradation after cell lysis and is suggested to be an indicator of active demyelination [7,8]. These ratios were almost normalized in the later stages after the stroke. In addition, the qualitative measurement of regional cerebrovascular reactivity to acetazolamide using split dose 131 I-IMP SPECT suggests the acetazolamide-enhanced vasoreactive perfusion of the right middle cerebral artery lesion recovered from 24% in the early stages to 70% at 6 months after the stroke (data not shown). These findings suggest that the neurons in the ischemic lesion were not functional but nevertheless still viable, so called, penumbra [9]. The increased NAA/Cr and decreased Cho/Cr ratios along with the improvement in cerebral perfusion suggest recovery of the neuronal cells and terminated demyelination processes in the ischemic penumbra. On the other hand, the lactate peak in MR spectroscopy was not shown with long TE, but was visible with short TE. Lactate is an indicator of anaerobic metabolism. In a previous MR spectroscopy study of patients with cerebral infarction, only the lactate signal was shown in the irreversible chronic ischemic tissue, however, multiple peaks including NAA, choline, creatine and lactate were detected in the ishemic penumbra [10]. Proton MR spectroscopy with short TE has the advantage of detection of additional metabolites with short T2-relaxation times, such as mobile lipids, proteins, myoinositol, glucose, glutamate, and glutamine [4,8]. Therefore, lactate including mobile lipids may be shown only in MR spectroscopy with short TE, nevertheless, other metabolites were detected with long TE in the present patient. There is no clear correlation between the metabolites of the acute stage of stroke and clinical outcome [7], therefore, further evaluation will be necessary to elucidate the prognostic potential of MR spectroscopy in childhood stroke. In this study, we examined a patient with occlusion of the right internal carotid artery with transient cerebral arteriopathy. Dissection of the artery was reversible and the clinical course of the patient was very good after treatment. Clinical improvement with relation to neuroimaging findings was unclear in our patient, however, the serial follow up using MR angiography and MR spectroscopy with long and short echo time was useful to evaluate the neuronal tissue for reversible vascular change with cerebral infarction in children. 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