ISCHEMIC STROKE IN A CHILD WITH COMPLEX CYANOTIC CONGENITAL HEART DISEASE

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1 13 CASE PRESENTATIONS ISCHEMIC STROKE IN A CHILD WITH COMPLEX CYANOTIC CONGENITAL HEART DISEASE Aniela Luminita Rugina 1, Violeta Streanga 1, Nicolai Nistor 1, Gabriela Buhusi 2, Ramona Filipescu 2, Irina-Mihaela Ciomaga 1 1 Gr. T. Popa University of Medicine and Pharmacy, Iasi 2 Sf. Maria Children Emergency Hospital, Iasi ABSTRACT Stroke is rare in children compared to adults. Most common causes of stroke in children are heart diseases that cause embolism and cerebral infarction and arteriovenous malformations for the brain hemorrhages, but a number of cases remain idiopathic, without being able to say precise etiology. The authors present the case of a child diagnosed in infancy with complex cyanotic heart malformation, but not operated, admitted with clinical and radiological signs of pneumonia, which evolved favorably with antibiotic and symptomatic therapy. During resolution of the pneumonia, the child becomes suddenly drowsy, presenting right hemiplegia, with absence of reflexes on the same side. Clinical examination correlated with cranio-cerebral CT have established the diagnosis of bilateral Sylvian ischemic stroke. The evolution was favorable under conservative treatment (antiplatelet drugs, physiotherapy), but right hemiplegia persisted. Keywords: ischemic stroke, congenital heart disease, child, hemiplegia INTRODUCTION Ischemic stroke is a rare pediatric emergency, the incidence being estimated to 2-3/ (1). Boys are twice as frequently affected than girls (12). While in adults the most frequent cause (80%) of stroke is atherosclerosis, in children there are many causes, the most common being embolic heart disease. The most frequent clinical manifestations are hemiplegia and convulsions. A lot of imaging techniques help to confirm the diagnosis: transfontanellar ultrasound, in newborn and infant, transcranial Doppler, CT, MRI. The chronology of these tests depends on the children s age and the availability in emergency, but MRI exam is the best (2). In children there is no standard treatment, compared to adults. Special attention should be paid to sequelae which occur in 70% of cases (motor, epileptic, cognitive) (3). However, the great plasticity of the brain at young age explains the unexpected recovery in contrast to the size of the brain infarct (2). CLINICAL CASE PRESENTATION SF, male, aged 1 year and 9 months, diagnosed in infancy with complex cyanotic congenital heart disease, is hospitalized for fever, rhinorrhea, nasal obstruction, productive cough with onset for 1 week. At 6 weeks of age the child was diagnosed with abdominal situs inversus, left atrial isomerism, single atrium, atrio-ventricular dual connection through a single atrioventricular valve, single ventricle - left ventricular type with double outlet, complete transposition of the great arteries, valvular and subvalvular pulmonary stenosis. Afterwards the infant was admitted four times to the Institute for Cardiovascular Diseases and Transplantation Târgu Mureş to determine whether surgery is convenient, but the family refused invasive preoperative investigations (transesophageal echocardiography, cardiac catheterization). On admission the child presented malaise, cyanosis, productive cough, pulmonary crepitation bilaterally, SaO 2 = 70% in the atmosphere, improved to 82% with oxy- Corresponding author: Violeta Streanga, Gr. T. Popa University of Medicine and Pharmacy, 16 Universitatii Street, Iasi streangavioleta@yahoo.com 288 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN 2014

2 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN gen, precordial bulge, apical impulse at the fourth left intercostal space in the midclavicular line, regular heart rate = 90/minute, systolic murmur grade 3 in the left parasternal area, BP = 95/55 mmhg, palpable peripheral pulse, cold extremities, liver located on the left, normal growth chart. Laboratory findings were noted: polycythemia, inflammatory syndrome; chest X-ray shows opacity in the left upper lung, heart flaunted on the diaphragm (Fig. 1). Electrocardiogram showed superior QRS axis (AQRS = -150 ) and right ventricular hypertrophy; echocardiography reveals stationary evolution of the cardiopathy. in the territory supplied by both middle Sylvian artery, more importantly on the left side (Fig. 4). FIGURE 2. Chest X-ray check-up a FIGURE 3. S.F., 1 year and 9 months. Right hemiplegia FIGURE 1. Chest X-ray, a postero-anterior, b lateral b The outcome of the respiratory disease was favorable after one week of treatment with antibiotics, anti-inflammatory and expectorants; chest x-ray showed the resolutive aspect of the pulmonary opacity, maintaining interstitial infiltration (Fig. 2). The child suddenly became drowsy, right hemiplegia occured; we ascertained the absence of reflexes on the same side and therefore we suspected cerebral infarction due to thrombo-embolism (Fig. 3). Cranial CT-scan revealed cerebral ischemic stroke FIGURE 4. Cranio-cerebral CT: left Sylvian ischemic stroke The neurosurgeon opted for medical treatment, as neurosurgical treatment was not mandatory at that time. The child received antiplatelet therapy and physiotherapy. He returns for annual reexamination and the persistence of right hemiplegia is aknowledged.

3 290 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN 2014 DISCUSSION The World Health Organization (WHO) defines stroke as a clinical syndrome characterized by a rapidly occurring focal or global disturbance of cerebral function, lasting more than 24 hours or leading to death, with no obvious nonvascular cause (4). This definition does not take into account, however, neuroimaging, considered now essential to determine the neurovascular origin of symptoms. Therefore, it is considered that the modern definition of stroke is a clinical syndrome characterized by: a neurological deficit related to the perfusion territory of a cerebral artery; neuroimaging evidence of an ischemic injury (5). This case falls within the age group most commonly affected by ischemic injury in childhood. Data shows that pediatric stroke is most frequently encountered between 1-5 years of age and rarely at extreme ages of childhood (under 1 year and over 15 years) (6). Up to 25% of ischemic strokes in children are due to heart disease, most cases being previously diagnosed with cardiac malformation. Stroke is more common in children with unoperated cardiac malformations. Thrombus may originate in the atria (eg. atrial septal defect + pulmonary hypertension), ventricle (eg. ventricular septal defect + pulmonary hypertension) or arterial (pulmonary arteriovenous fistula) (7). Both in adult and in child, cerebral ischemia results from decreased cerebral blood flow (CBF), mostly related to the occlusion of a cerebral artery by embolic material. The consequences of this tissue hypoperfusion depend on its duration and intensity (8). The cerebral ischemia area can be divided schematically into three parts, from the periphery to the center: a moderate ischemia area, where the reduction of cerebral perfusion has no clinical expression; an area of shadows where CBF is still sufficient to ensure an energy supply for cell survival, but not enough to enable their operation; this area is responsible for the neurological deficit; an area of necrosis, caused by an impaired cellular defense system to hypoxia and cell death; this area is responsible for constituted neurological deficit, which persists even if normal CBF is early restored. Ischemia is responsible for anaerobic glycolysis, intracellular acidosis and intracellular calcium inflation due to disruption of calcium channel receptors (2). Clinical symptoms vary depending on the age of the child. Thus, the onset is brutal under the age of 10 years, mostly by occurrence of hemiplegia (as in the case presented) and/or seizures, often generalized; after this age, clinical symptoms are close to those seen in adults (9). Diagnosis is confirmed by neuroimaging, which reveals vessel obstruction, as well as the extent and location of ischemic lesions. In the presented case, ischemic lesions were large, computed tomography showing hypodense areas in the superficial and deep territory supplied by the left middle cerebral artery (Sylvian) (Fig. 4) but also in the superficial territory supplied by the right Sylvian artery. We proceeded to: upright positioning the patient in order to improve venous return and to reduce the risk of inhalation pneumonia; monitoring vital signs and the level of consciousness; platelet administration. For patients with acute stroke, anticoagulants (unfractionated heparin or heparinoids) are not indicated; only antiplatelet agents can be used. Secondary prevention with anticoagulation therapy may be initiated in the event of transient ischemic attack or minor cerebral infarction in patients presenting embolic heart with high risk of relapsing. Therapy should be initiated immediately or within days, if there are no contraindications. Intravenous thrombolysis in child is practiced only sporadically in some well-equipped centers, this technique not being validated in patients under 18 years of age. For treatment of intracranial hypertension due to cerebral infarction or cerebral hemorrhage, mannitol, glycerol, furosemide, hypertonic solutions and corticosteroids are not recommended (3). The patient we presented had survived, but with sequelae (hemiplegia). The literature shows that infant mortality of stroke is about 16%; it can increase to 40% if previous severe disease exist (10). Moderate or severe hemiplegia is found in 42% of cases. Other waste disorders include: dysphasia, in the case of right brain impairment, and ataxia, in the event of damage to the rear. Regarding cognitive development, it seems that patients who have suffered an ischemic stroke have a normal IQ value (85-95), but may have impaired attention and memory, visual-spatial function disorders and reduced quality of life in adolescence (11,12). CONCLUSIONS Ischemic stroke, although rare in children, should be considered in patients with known con-

4 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN genital heart malformations, especially cyanogens, if hemiplegia or seizures occur suddenly without another cause. Neuroimaging examination reveals the location and the extent of ischemic lesions, which determine the therapeutic decision upon the acute phase and the recovery of possible sequelae. REFERENCES 1. Janjua N., Nasar A., Lynch J.K., Qureschi A.I. Thrombolysis for ischemic stroke in children: data from the nationwide inpatient sample. Stroke. 2007; 38: Béjot Y., Hervieu M., Osseby G.V. et al. Les accidents vasculaires cérébraux chez l enfant: pourquoi y penser? 52 e Congrès National d Anésthesie et de Réanimation Médecin. Urgences vitales, SFAR Bollaert P.E., Vinatier I., Orlikowski D., Meyer P. Prise en charge de l accident vasculaire cérébral chez l adulte et l enfant par le réanimateur (nouveau-né exclu), (hémorragie méningée exclue). Réanimation 2010; 19: Aho K., Harmsen P., Hatano S. Cerebrovascular disease in the community: results of a WHO collaborative study, Bulletin of the World Health Organization 1980; 58(1): Group TPSW, Ed., Stroke in Childhood. Clinical Guidelines for Diagnosis, Management and Rehabilitation. The Lavenham Press, Suffolk, UK, Lee Y.Y., Lin K.L., Wang H.S. et al. Risk factors and outcomes of childhood ischemic stroke in Taiwan. Brain Dev 2008; 30 (1): Kumar K. Neurological complications of congenital heart disease. Indian J Pediatr 2000; 67: Leys D., Pruvo J.P. Strategie pratique en urgence face a un AVC. EMC - Neurologie 2002; A50: Lopez-Vicente M., Ortega-Gutierrez S., Amlie-Lefond C., Torbey M.T. Diagnosis and management of pediatric arterial ischemic stroke. J Stroke Cerebrovasc Dis 2010; 19(3): Adams R.J., Brambilla D. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med 2005; 353: Pavlovic J., Kaufmann F., Boltshauser E. Neuropsychological problems after paediatric stroke: two year follow-up of Swiss children. Neuropediatrics 2006, 37(1): Steilin M., Wwhrli E. L accident vasculaire ischémique en pédiatrie. Quand y penser- quoi faire! Paediatrica 2009; 20 (2) :

5 13 PREZENTĂRI DE CAZ ACCIDENT VASCULAR CEREBRAL ISCHEMIC LA UN COPIL CU CARDIOPATIE CONGENITALĂ CIANOGENĂ COMPLEXĂ Aniela Luminiţa Rugină 1, Violeta Ştreangă 1, Nicolai Nistor 1, Gabriela Buhuşi 2, Ramona Filipescu 2, Constantin Iordache 1, Irina-Mihaela Ciomaga 1 1 Universitatea de Medicină şi Farmacie Gr. T. Popa, Iaşi 2 Spitalul de Urgenţă pentru Copii Sf. Maria, Iaşi REZUMAT Accidentul vascular cerebral (AVC) este rar la copil comparativ cu adultul. Cauzele cele mai comune de AVC la copil sunt cardiopatiile emboligene pentru infarctul cerebral şi malformaţiile arteriovenoase pentru hemoragiile cerebrale, dar un număr de cazuri rămân idiopatice, fără a li se putea afi rma etiologia precisă. Autorii prezintă cazul unui copil diagnosticat în perioada de sugar cu malformaţie congenitală de cord cianogenă complexă, dar neoperată, internat cu semne clinice şi radiologice de pneumonie, care a evoluat favorabil sub tratament antibiotic şi simptomatic. În timpul perioadei rezolutive a pneumoniei, copilul devine brusc somnolent, prezentând hemiplegie dreaptă cu absenţa refl exelor de aceeaşi parte. Examenul clinic corelat cu CT cranio-cerebral au stabilit diagnosticul de AVC ischemic sylvian bilateral. Evoluţia a fost favorabilă sub tratament conservator (antiagregante plachetare, fizioterapie), persistând însă hemiplegia dreaptă. Cuvinte cheie: accident vascular ischemic, malformaţie congenitală cardiacă, copil, hemiplegie INTRODUCERE Accidentul vascular cerebral (AVC) ischemic este o urgenţă pediatrică rară, incidenţa estimată fiind 2-3/ (1). Băieţii sunt de două ori mai frecvent afectaţi decât fetele (12). În timp ce la adult în 80% dintre cazuri este determinat de ateroscleroză, la copil cauzele sunt multiple, cele mai comune fiind cardiopatiile emboligene. Clinic, cel mai frecvent se manifestă prin hemiplegie sau convulsii. Diverse tehnici imagistice contribuie la confirmarea diagnosticului: ecografia transfonta nelară la nou-născut şi sugar, doppler transcranian la copil, CT, RMN. Cronologia acestor examene depinde de vârstă şi de disponibilitatea lor în ur genţă, dar RMN constituie examenul cel mai per formant (2). La copil, faţă de adult, nu există un tratament standardizat. O atenţie deosebită trebuie acordată sechelelor care apar în 70% dintre cazuri (motorii, epileptice, cognitive) (3). Însă marea plas ticitate a creierului la vârsta mică explică recu perarea uneori neaşteptată în contrast cu întinderea mare a zonelor de infarct cerebral (2). PREZENTAREA CAZULUI CLINIC S.F., sex masculin, în vârstă de 1 an şi 9 luni, diagnosticat în perioada de sugar cu cardiopatie congenitală complexă cianogenă, se internează pentru febră, rinoree, obstrucţie nazală, tuse pro ductivă, cu debut de 1 săptămână. La vârsta de 6 săptămâni a fost diagnosticat cu situs inversus ab dominal, izomerism atrial stâng, atriu unic, dublă conexiune atrio-ventriculară printr-o valvă atrio-ventriculară unică, ventricul unic de tip ventricul stâng, cu dublă cale de ieşire, D-transpoziţie de vase mari, stenoză pulmonară valvulară şi sub valvulară. Ulterior sugarul a mai avut 4 internări la Institutul de Boli Car dio vasculare şi Transplant Târgu-Mureş pentru stabilirea oportunităţii inter venţiei chirurgicale, însă familia a refuzat efectuarea investigaţiilor invazive preoperatorii (ecocar dio grafia transesofagiană, ca- Adresa de corespondenţă: Asist. Univ. Dr. Violeta Ştreangă, Universitatea de Medicină şi Farmacie Gr. T. Popa, Str. Universităţii nr. 16, Iaşi streangavioleta@yahoo.com 348 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN 2014

6 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN te terismul cardiac). La in ternare copilul prezenta stare generală influenţată, cianoză generalizată, tuse productivă, pulmonar raluri subcrepitante bilateral, SaO 2 = 70% în aerul atmosferic, ameliorată la 82% sub oxigenoterapie, arie precordială bombată, şoc apexian în spaţiul IV intercostal stâng pe linia medioclaviculară, zgomote cardiace ritmice, cu frecvenţa = 90/minut, suflu sistolic gradul III/VI parasternal stâng, TA = 95/55 mmhg, puls periferic prezent, extremităţi reci, ficat la rebordul costal stâng, dezvoltare staturo-pon de rală şi psiho-motorie corespunzătoare vârstei. Paraclinic s-au remarcat: poliglobulie, sindrom inflamator prezent; radiologic: opacitate la nivelul lobului pulmonar superior stâng cu proiecţie posterioară pe radiografia de profil, cord etalat pe diafragm (Fig. 1). Electrocardiograma a obiectivat axă antiapicală (A QRS = 150 ), suprasolicitare ventriculară dreaptă, echocardiografic apreciindu-se evoluţia staţionară a cardiopatiei. După o săptămână de tratament cu antibiotice, antiinflamatorii şi fluidifiante, evoluţia afecţiunii res piratorii era favorabilă clinico-radiologic, constatându-se aspect rezolutiv al opacităţii descrise, menţinându-se infiltraţia interstiţială (Fig. 2). Brusc, însă, copilul a devenit somnolent, prezentând hemiplegie dreaptă cu absenţa reflexelor de aceeaşi parte, suspicionându-se infarctul cerebral secundar trombemboliei (Fig. 3). Examenul CT cranio-cerebral a evidenţiat AVC ischemic sylvian bilateral, mai important pe partea stângă (Fig. 4). FIGURA 2. Radiografi e cardiotoracică de control a FIGURA 3. S.F., 1 an şi 9 luni. Hemiplegie dreaptă FIGURA 1. Radiografi e cardio-toracică; a faţă; b profi l b FIGURA 4. CT cranio-cerebral: accident vascular cerebral ischemic sylvian stâng

7 350 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN 2014 Medicul neurochirurg a opinat pentru tratament medical, neexistând indicaţie de tratament neurochirurgical în acel moment. Copilul a primit tra tament cu antiagregante plachetare şi a efectuat recuperare medicală constând din fiziokinetoterapie. Revine anual la control, în prezent persistând he miplegia dreaptă. DISCUŢII OMS defineşte AVC ca fiind un sindrom clinic caracterizat printr-o tulburare focală sau globală a funcţiei cerebrale survenită rapid, care durează peste 24 de ore sau duce la deces, fără o cauză nonvasculară evidentă (4). Această definiţie nu ţine cont, însă, de neuroimagistică, considerată, în prezent, esenţială pentru a stabili originea neuro vasculară a simptomelor. De aceea, în definiţia modernă se consideră că AVC este un sindrom clinic caracterizat prin: deficit neurologic în relaţie cu perfuzia teritoriului unei artere cerebrale; dovada neuroimagistică a leziunii ischemice (5). Cazul prezentat se încadrează în grupa de vârstă cel mai frecvent afectată de accidentele ischemice la vârsta copilăriei. Datele din literatură arată că AVC ischemic în pediatrie este întâlnit cel mai frecvent la grupa de vârstă 1-5 ani şi mai rar la vârstele extreme ale copilăriei (sub 1 an şi peste 15 ani) (6). Până la 25% din AVC ischemice la copii sunt datorate unor afecţiuni cardiace, majoritatea cazurilor fiind deja diagnosticate anterior cu malformaţie cardiacă. AVC este mai frecvent la copiii cu malformaţii cardiace necorectate chirurgical. Embolii pot proveni de la nivel atrial (ex. DSA + HTAP), ventricular (ex. DSV + HTAP) sau arterial (fistule arteriovenoase pulmonare) (7). Ca şi la adult, ischemia cerebrală rezultă din scă derea debitului sanguin cerebral (DSC), cel mai ade sea în raport cu obstrucţia unei artere cerebrale cu ma terial embolic. Consecinţele tisulare ale acestei hi poperfuzii depind de durata şi intensitatea sa (8). Zona de ischemie cerebrală poate fi divizată sche matic în trei părţi, începând de la periferie spre centru: o zonă de ischemie moderată, unde reducerea perfuziei cerebrale nu are nici o exprimare clinică; o zona de penumbră, unde DSC este încă suficient pentru a asigura un aport energetic ce permite supravieţuirea celulelor, dar insuficient pentru a permite funcţionarea lor; această zonă este responsabilă de deficitul neurologic; o zonă de necroză, traducând o insuficienţă a sistemului de apărare celulară cu hipoxie şi moarte celulară, responsabilă de un deficit neurologic constituit, ce persistă chiar şi în caz de restabilire precoce a unui DSC normal. Ischemia este responsabilă de glicoliza anaerobă, de acidoza intracelulară şi, prin perturbarea receptorilor canalelor de calciu, de o inflaţie calcică intracelulară (2). Simptomatologia clinică este variabilă în funcţie de vârsta copilului. Astfel, sub vârsta de 10 ani debutul este brutal, mai frecvent prin apariţia unei hemiplegii (ca şi la cazul prezentat), sau/şi convulsii, adesea generalizate; după această vârstă simptomatologia clinică este apropiată de cea întâlnită la adult (9). Diagnosticul este confirmat de neuro imagistică, prin obiectivarea vasului obstruat, a întinderii şi localizării leziunilor ischemice. La cazul prezentat, leziunile ischemice au fost întinse, examenul CT evidenţiind arii hipodense în teritoriul superficial şi profund irigat de artera cerebrală medie (sylviană) stângă (Fig. 4) dar şi în teritoriul superficial irigat de artera sylviană dreaptă. Atitudinea a constat în poziţionare cu capul ridicat pentru a ameliora returul venos şi a diminua riscul de pneumonie de inhalaţie, monitorizarea semnelor vitale şi a stării de conştienţă şi administrarea de anti agregante plachetare. Experţii recomandă doar antiagregante plachetare, anticoagulantele (heparina nefracţionată sau heparinoizii) nefiind indicate în infarctul acut. Tratamentul de prevenţie secundară cu anticoagulante se poate iniţia în caz de accident ischemic tranzitor sau infarct cerebral minor, la pacienţii ce prezintă o cardiopatie emboligenă cu risc înalt de recidivă, imediat sau în primele zile, dacă nu există contraindicaţii. Tromboliza intravenoasă se practică sporadic la copil doar în unele centre bine dotate, nefiind validată la pacientul sub 18 ani. În hi pertensiunea intracraniană din infarctul cerebral sau hemoragia cerebrală nu sunt recomandate: manitol, gli cerol, furosemid, soluţii hipertone şi corticoizi (3). Pacientul prezentat a supravieţuit, dar cu sechele (hemiplegie). Datele din literatură arată că mortalitatea în AVC la copil este de aproximativ 16%, putând creşte la 40% în caz de boli grave preexistente (10). Hemiplegia medie sau severă este întâlnită în 42% dintre cazuri. Alte tulburări re ziduale pot fi: disfazia, în cazul afectării emisferului drept şi ataxia, în caz de leziuni posterioare. În ceea ce priveşte dezvoltarea cognitivă, se pare că pa-

8 REVISTA ROMÂNÅ DE PEDIATRIE VOLUMUL LXIII, NR. 3, AN cienţii ce au suferit un AVC ischemic au o valoare a QI normală (85-95), dar pot prezenta tulburări de atenţie, de memorie, tulburări ale funcţiei vizuospa ţiale şi diminuarea calităţii vieţii la vârsta adolescenţei (11,12). CONCLUZII AVC ischemic, deşi este o entitate rară la copil, trebuie evocat la pacientul cunoscut cu o malformaţie congenitală de cord în special cianogenă, la care se instalează, de obicei brusc, o hemiplegie, sau la care apar convulsii fără o altă cauză. Examenul neuroimagistic precizează întinderea şi localizarea leziunilor ischemice, în funcţie de care se adoptă decizia terapeutică pentru faza acută şi ulterior pentru recuperarea eventualelor sechele.

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