61 Received June 2, 2001. Accepted for publication July 17, 2001. Reversible Vascular Changes in Children With Cerebral Infarction Address correspondence to Dr John B. Bodensteiner, Division of Pediatric Neurology, Children’s Health Center and Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, 500 West Thomas Road, Suite 930, Phoenix, AZ 85013. Tel: 602-406-3808; fax: 602-406-3810; e-mail: jbo- ABSTRACT dens@chw.edu. A case of cerebral infarction in a 4-year-old male is described. The child presented with an acute onset of right hemiplegia, central facial References 1. Hruska KA, Slatopolsky E: Disorders of phosphorus, calcium and magnesium metabolism, in Schrier RW, Gottschalk CW (eds): Diseases of the Kidney, 6th ed. Boston, Little-Brown, 1997, 2477-2526. 2. Fishman RA: Neurological aspects of magnesium metabolism. Arch Neurol 1965;12:562-569. 3. Rude RK, Singer FR: Magnesium deficiency and excess. Ann Rev Med 1981;32:245-259. 4. Yu ASL: Disturbances of magnesium metabolism, in Brenner B (ed): Brenner and Rector’s The Kidney, 6th ed. Philadelphia, WB Saunders, 5. Tsau Y, Tsai W, Lu FL, et al: Symptomatic hypomagnesemia in children. Acta Paediatr Sin 1998;39:393-397. 6. Muldowney FP, McKenna TJ, Kyle LH, et al: Parathormone-like effect of magnesium replenishment in steatorrhea. N Engl J Med 1970;282:61-68. Dudin KI, Teebi AS: Primary hypomagnesemia. Eur J Pediatr 1987;146:303-305. Evans RA, Carter JN, George CRP: The congenital magnesium-losing kidney. QJM 1981;197:39-52. Bettinelli A, Bianchetti MG, Girardin E, et al: Use of calcium excretion values to distinguish two forms of primary renal tubular hypokalemic alkalosis: Bartter and Gitelman syndromes. J Pediatr 1992;120:38-43. Avoli M, Louvel J, Pumain R, et al: Seizure-like discharges induced by lowering [Mg2+] in the human epileptogenic neocortex maintained in 2000, 1055-1070. 7. 8. 9. 10. vitro. Brain Res 1987;417:199-203. 11. 12. 13. 14. 15. 16. 17. Mody I, Lambert JD, Heinemann U: Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices. J Neurophysiol 1987;57:869-888. Vallee BL, Wacker WEC, Ulmer DD: The magnesium-deficiency tetany syndrome in man. N Engl J Med 1960;262:155-161. Nuytten D, Van Hees J, Meulemans A, et al: Magnesium deficiency as a cause of acute intractable seizures. 1991;238:262-264. J Neurol Chutkow JG, Meyers S: Chemical changes in the cerebrospinal fluid and brain in magnesium deficiency. Neurology 1968;18:963-974. Ahsan SK, Al-Swoyan S, Hanif M, Ahmad M: Hypomagnesemia and clinical implications in children and neonates. Indian J Med Sci 1998;52:543-554. Estep H, Shaw WA, Watlington C, et al: Hypocalcemia due to hypomagnesemia and reversible parathyroid hormone unresponsiveness. J Clin Endocrinol 1969;29:842-848. Dingledine R, McBain CJ: Excitatory amino acids neurotransmitters, in Siegel GJ (ed): Basic Neurochemistry. New York, Raven Press, 1994, 367-387. 18. 19. 20. 21. 22. Duarte CG: Effects of ethacrynic acid and furosemide on urinary calcium, phosphate, and magnesium. Metabolism 1968;17:867-876. Wacker WEC, Vallee BL: A study of magnesium metabolism in acute renal failure employing a multichannel flame spectrometer. N Engl J Med 1957;257:1254-1262. Bappal B, Raghupathy P, Rajendran Nair TM, et al: External hydrocephalus in primary hypomagnesemia: A new fmding. Arch Dis Child 1999;81:505-507. Morgan JD, Painter MJ: Neonatal seizures, in Swaiman KF, Ashwal S (eds): Pediatric Neurology: Principles and Practice. St. Louis, Mosby, 1999, 183-190. Siberry GK, Iannone R: The Harriet Lane Handbook, 15th ed. St. Louis, Mosby, 2000. palsy, and dysarthria. He had no predisposing factors for cerebral infarction. A computed tomography scan showed a diffuse low-density area in the territory of the left middle cerebral artery. Magnetic resonance angiography disclosed multiple irregular narrowings in the left anterior and middle cerebral arteries. He recovered spontaneously from the stroke with minimal long-term complications, and repeated angiography disclosed a complete regression of the vascular changes 2 months after the stroke. There was no recurrence of stroke after 2-year follow-up. This case demonstrates the importance of longitudinal angiographic follow-up in childhood cerebral infarction of idiopathic origin. (J Child Neu2002;17:61-63). rol Cerebral infarction is rare in childhood. Although several predisposing factors, such as trauma, cyanotic heart disease, and coagulation disorders, are described, precise etiology is not established in most of the pediatric cases.’-3 A recent report shows that a high proportion of cerebrovascular disease comprises idiopathic cerebral infarction, termed transient cerebral arteriopathy.4 We present a case of cerebral cortical infarction in which magnetic resonance angiography showed reversible cerebral vascular narrowings, which are multiple and irregular. By reviewing the past records with cerebral infarction of unknown etiology, we surveyed the clinical characteristics of three cases of cerebral infarction, evolving to the unilateral cortical lesion, because of transient cerebral vascular changes. Angiography disclosed multifocal lesions of the arterial wall (focal stenosis and narrowings), which normalized within 2 months. We regard them as one of the clinical variants of idiopathic cerebral infarction of children. Case Report This 4-year-old boy suddenly developed muscle weakness of his right upper and lower extremities and disturbance of speech. He had no history of migraine or preceding febrile illnesses. On admission, vital signs were normal and neurologic examination demonstrated mild right hemiparesis, right facial nerve palsy, and motor aphasia. Deep tendon reflexes were hypoactive, especially of the right side. Physical findings were otherwise normal. He had no known risk factors for cerebral infarction such as con- genital heart disease or hematologic or metabolic diseases. He also was not receiving any medications. A cranial computed tomography (CT) scan showed a diffuse low-density area in the left temporal area. Magnetic resonance imaging (MRI) revealed that the infarcted area comprised a territory of the left anterior and middle cerebral arteries involving the basal ganglionic structures (Figure 1). Magnetic resonance angiography disclosed irregular narrowing lesions in the left internal carotid artery through the anterior and middle cerebral arteries (Figure 2A). A right-sided magnetic resonance angiography was normal. There was no collateral circulation. Routine laboratory fmdings on admission were normal, including serum chemistry and coagulation tests, such as prothrombin time, activated partial Downloaded from jcn.sagepub.com at OAKLAND UNIV on June 9, 2015 62 motor and expressive speech were almost normal, apart from a slight right- sided spasticity. Discussion Cerebral infarction is rare in childhood. The main predisposing factor is trauma, and the relatively frequent causes are cardiac emboli caused by cyanotic heart diseases, neonatal distress, and infections. But most cases occur in the absence of such predisposing factors and are regarded as idiopathic. 1-3 The disease involving cervicocephalic arteries includes chronic vasculopathies dominated by moyamoya disease or fibromuscular dysplasia, cervical traumatic dissections, and acute intracranial arteriopathies of obscure origin. 1,4,1 Chabrier et al proposed that one quarter of those idiopathic cases comprise transient cerebral arteriopathy,4 which is characterized by (1) occurrence without apparent predisposing factors, (2) conventional angiograms showing intracranial arterial lesion of unknown etiology, and (3) cerebral imaging showing small subcortical infarcts located in the basal ganglia or internal capsule. Interestingly, a long-term clinical and angiographic follow-up demonstrated the lack of late recurrence of stroke and reversion or stabilization of arterial lesions. In this case, acute hemiplegia occurred in the absence of known predisposing factors. At the time of admission, magnetic res- Figure 1. T 2-weighted magnetic resonance image showing a hyperintense lesion in the left middle cerebral artery territory including lacunar areas. thromboplastin time, fibrinogen, plasminogen, antithrombin III, and protein C and S levels. Antinuclear antibodies, antiphospholipid antibodies, and anticardiolipin antibody were negative. Serum amino acid analysis and plasma lactate and pyruvate levels were also normal. Serologic examination failed to show the antecedent infection of varicella-zoster virus. Electrocardiography and echocardiography were normal. Magnetic resonance angiography of the renal vessels was normal. An electrocardiogram showed left-sided high-voltage slow-wave activities at the site of corresponding infarcted areas, and a rebuild-up was not induced on hyperventilation. The occlusive vascular lesions were still detected on a 2-week follow-up magnetic resonance angiography. The angiographic pictures (ie, multiple irregular cerebral vascular narrowings) raised a suspicion of intracranial fibromuscular dysplasia or arterial dissection. The patient was then placed on a low-dose aspirin to prevent stroke recurrence, and a rehabilitation program was started. Two months later, however, magnetic resonance angiography (Figure 2B) disclosed a spontaneous regression of the vascular lesions. On the longitudinal follow-up at 4, 6, and 12 months after the stroke, the irregular vascular narrowings were no longer detected on magnetic resonance angiography. The clinical course was favorable, and 2 years after onset, his gross Table 1. onance angiography presented multiple luminal vascular narrowings in the left internal carotid artery through the anterior and middle cerebral arteries. At the initial presentation, intracranial fibromuscular dysplasia or arterial dissection was presumed in the diagnostic concern, and then the patient was placed on low-dose aspirin to prevent stroke recurrence, and an indication for surgical revascularization was discussed. Two months later, however, the angiographic nature of reversibility of vascular changes allowed us to withdraw aspirin. His clinical picture resembled that of transient cerebral arteriopathy.4 Table 1 summarized clinical profiles of the three children suffering from idiopathic cerebral infarction with reversible vascular changes with a diffuse cortical infarction.6,7 All of these patients showed an acute onset of symptoms, and the impending ischemic stroke was never heralded by transient neurologic defects, which are commonly encountered among adult patients. None of them had a history of head injury or signs of infection. No predisposing factors could be clarified. Angiographic evaluations were performed in all patients, and multiple vascular narrowings were found in the unilateral side of the infarction, Summary ofThree Cases of Idiopathic Cerebral Infarction Caused by Reversible Vascular Changes in Children M1 = horizontal portion of the middle cerebral artery; C1 = terminal tract of the carotid siphon; A1 lorigin of the anterior cerebral artery; VZV described. Downloaded from jcn.sagepub.com at OAKLAND UNIV on June 9, 2015 = varicella zoster virus; ND = not 63 In the clinical setting, magnetic resonance angiography is preferred, along with MRI, but there is limited information concerning the diagnostic value of magnetic resonance angiography. Rollin et al indicated catheter angiography other than magnetic resonance angiography when cortical infarcts are seen with MRI with or without basal ganglia infarcts since magnetic resonance angiography is not sensitive to small vessel disorders.’ Further studies are necessary to confirm the angiographic nature of the vascular changes, especially in the case of the idiopathic infarction. Idiopathic cortical infarction could be treated conservatively since the reversibility of the arterial lesions may be expected as exemplified by these three patients. Vigorous clinical evaluation and longitudinal angiography are warranted to make a precise diagnosis and determine an appropriate treatment strategy. Kenichiro Kobayashi, MD Mieko Yoshioka, MD, PhD Masaru Yamakawa, MD, PhD Masaru Kubota, MD, PhD Toshikazu Nishio, MD, PhD Department of Pediatrics Kobe City General Hospital Chuo-ku, Kobe, Japan Received May 9,2001. Received revised August 24,2001. Accepted for publication August 24, 2001. Address correspondence to Dr Kenichiro Kobayashi, Department of Pediatrics, Kobe City General Hospital, 4-6, Minatojima-Nakamachi,Chuoku, Kobe 6500046, Japan. Tel: 0081-78-302-4321; fax: 0081-78-302-7537; e-mail: kenichiro_kobayashi@medical.general.hp.city.kobe.jp. Figure 2. A, Magnetic resonance angiography showing irregular narrowings in the left terminal tract of the carotid siphon and left horizontal portion of the right middle cerebral artery. B, Follow-up magnetic resonance angiography showing a normalization of the left vascular lesions.The multiple narrowings are no longer visible. which surprisingly resolved spontaneously in 2 months. Early clinical recovery was noticeable in all cases with varying degrees References 1. Riela AR, Roach ES: Etiology of stroke in children. J Child Neurol 2. Satoh S, Shirane R, Yoshimoto T: Clinical survey of ischemic cerebrovascular disease in children in a district of Japan. Stroke 1993;8:201-220. 3. 4. of restitution over the following week and presented virtually no neurologic sequelae, except a slight unilateral spasticity. All fulfilled diagnostic criteria of transient cerebral arteriopathy, except for extensive cortical infarctions. Therefore, we propose that the above cases, including ours, may represent a clinical variant of transient cerebral arteriopathy, as described by Chabrier et al.1 They also have an outstanding clinical point in that they had a relatively benign course, although they showed more extensive infarcted areas, not only in the basal ganglia but also in the cortical and subcortical lesions. Even though vari- 5. 6. 7. 8. cella-zoster virus infection is regarded as a significant risk factor for idiopathic arterial ischemic strokes, the serologic examination failed to show the antecedent infection of varicella-zoster virus except for one case, in whom the virus titers 8 were not described 9. 1991;22:586-589. Raybaud CA, Livet MO, Jiddane M, Pinsard N: Radiology of ischemic strokes in children. Neuroradiology 1985;27:567-578. Chabrier S, Rodesch G, Lasjaunias P, et al: Transient cerebral arteriopathy : A disorder recognized by serial angiograms in children with stroke. J Child Neurol 1998;13:27-32. Emparanza JI, Aldamiz-Echevarria L, Perez-Yarza E, et al: Ischemic stroke due to fibromuscular dysplasia. Neuropediatrics 1989;20:181-182. Nakamura M, Hanaoka Y, Matsuzaki S, et al: A case of pediatric cerebral infarction presenting with "string of beads" appearance in the middle cerebral artery. Shonika-Rinsho 1993;56:1733-1737. Mancuso P, Chiaramonte I, Carpinteri M, et al: Idiopathic middle cerebral artery occlusion in children: Report on three cases. Childs Nerv Syst 1994;10:131-134. Sebire G, Meyer L, Chabrier S: Varicella as a risk factor for cerebral infarction in childhood: A case-control study. Ann Neurol 1999;45:679-680. Rollins N, Dowling M, Booth T, Purdy P: Idiopathic ischemic cerebral infarction in childhood: Depiction of arterial abnormalities by MR angiography and catheter angiography. AJNR Am J Neuroradiol 2000;21:549-556. Downloaded from jcn.sagepub.com at OAKLAND UNIV on June 9, 2015