Case Report Pediatr Neurosurg 2002;37:158–163 Received: February 28, 2002 Accepted: May 10, 2002 Stroke and Pediatric Human Immunodeficiency Virus Infection Case Report and Review of the Literature Prithvi Narayan Owen B. Samuels Daniel L. Barrow Emory University School of Medicine, Atlanta, Ga., USA Key Words Stroke W Cerebrovascular accidents W HIV W AIDS Abstract Stroke is an uncommon complication in pediatric patients with acquired immunodeficiency syndrome (AIDS). However, with the increasing life span of this patient population, more cases of stroke are being reported. We report the case of a 13-year-old girl with a known history of AIDS who presented with new-onset seizures and right hemiparesis. Serial imaging studies revealed progressive occlusion of the left middle cerebral artery and both anterior cerebral arteries with development of collateral circulation. The workup for other etiologies of stroke was negative. This nonatherosclerotic occlusive disease is most likely secondary to vasculopathy caused by the human immunodeficiency virus (HIV). HIV infection should be included in the differential diagnosis of children who present with seizures, mental status change or focal neurological deficits. Treatment options are limited. The different prognoses associated with the etiologies of stroke in this patient population mandate a careful and thorough evaluation. Copyright © 2002 S. Karger AG, Basel ABC © 2002 S. Karger AG, Basel 1016–2291/02/0373–0158$18.50/0 Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Accessible online at: www.karger.com/journals/pne Introduction As the life expectancy of children infected with the human immunodeficiency virus (HIV) increases, various patterns of neurological dysfunction are being reported [1–4]. Central nervous system (CNS) involvement may be due to acquired immunodeficiency syndrome (AIDS) or HIV-related encephalopathy or secondary to complications related to the immunodeficiency. The latter category includes CNS infections, CNS neoplasms and strokes. Ischemic or hemorrhagic stroke is a well-recognized complication of HIV infection in adults [5, 6] but is an uncommon occurrence in children. This report describes the case of a 13-year-old child with AIDS who suffered a stroke. The etiology of strokes in this group of patients is discussed along with a review of the pertinent literature. Case Report A 13-year-old girl with a known history of AIDS and a low CD-4 count presented with new onset of partial complex seizures. On examination, the patient was awake, alert and dysphasic, with a right facial palsy and right hemiparesis. There were brisk deep tendon reflexes and an extensor plantar response on the right. A computed tomography (CT) scan of the head revealed subacute hemorrhage involving the left basal ganglia (fig. 1a) and edema of the left tempo- Daniel L. Barrow, MD, Chairman Department of Neurological Surgery Emory University School of Medicine 1365-B Clifton Road, NE, Ste. 6400, Atlanta, GA 30322 (USA) Tel. +1 404 778 5770, Fax +1 404 778 4472, E-Mail daniel_barrow@emoryhealthcare.org Fig. 1. CT of the head (a) and axial T1weighted MRI of the brain (b) showing a lesion in the left basal ganglia most likely representing a subacute hemorrhage. ral lobe (not shown). Magnetic resonance imaging (MRI) of the brain confirmed the findings on the head CT but was negative for other structural lesions (fig. 1b). A 4-vessel cerebral angiogram showed a complete occlusion of the left middle cerebral artery (MCA) with fusiform dilatation of the left internal carotid artery proximal to the ophthalmic artery and extending into the left A1 segment (fig. 2). There was retrograde filling of some of the larger branches of the distal Sylvian region of the MCA. The laboratory and clinical workup revealed no evidence of acute infection or coagulopathy. The patient had an uneventful hospital course. At the time of discharge, her right hemiparesis had improved and the patient was ambulating with a cane. The patient presented 2 weeks after discharge with sudden worsening of her right hemiparesis. An MRI and magnetic resonance angiography (MRA) of the brain were obtained and showed a new large left frontal lobe nonhemorrhagic infarction with occlusion of both anterior cerebral arteries (ACAs) (fig. 3). The patient’s condition remained stable for the remainder of the hospital stay. Stroke is a complication of HIV infection in approximately 1% of affected children [7] and can be the initial presentation of HIV infection in some cases [8]. Autopsy studies have documented a cerebral infarction in 10–30% of children with HIV or AIDS [4]. Due to the lack of welldesigned case-control studies, the association between stroke and HIV infection is unclear [9]. To address this issue, Qureshi et al. [10] conducted a retrospective review of 236 adult patients with stroke. Among patients with stroke, cerebral infarction was more common in HIV-positive patients than in HIV-negative patients (80 vs. 56%, p = 0.04). Their findings suggest an increased risk of stroke associated with HIV infection [10]. The major causes of stroke in HIV-infected patients include cardioembolism, infection, coagulopathy, thrombocytopenia and vasculitis. However, the etiology is unknown in a number of cases, and a vasculopathy of some form has been implicated [4, 11]. Table 1 summarizes the characteristics of stroke in HIV-infected children reported in the literature. Cardiac disease is commonly associated with cerebral embolism. This may include rheumatic heart disease, prosthetic heart valve, bacterial endocarditis, atrial myxoma and myocarditis [12]. Opportunistic infections can cause vasculopathy and subsequently lead to cerebral infarction [7, 13]. Pathogens that have a propensity for angioinvasion and secondary thrombosis of the infected vessels include Candida albicans, cytomegalovirus and varicella-zoster virus. Opportunistic infections of the CNS are less common in children compared to adults [14]. Fulmer et al. [13] reported two cases of fusiform cerebral aneurysms in HIV-positive children and the first reported case of an aneurysm associated with varicellazoster vasculitis. Lymphoma is a known neoplastic cause of vasculopathy in AIDS patients. The tumor can invade blood vessels, causing vascular injury and occlusion [7]. As with opportunistic infections, primary CNS lymphoma is unusual in children. Stroke and Pediatric HIV Infection Pediatr Neurosurg 2002;37:158–163 Discussion 159 A number of coagulopathies have been associated with HIV infection. Thrombocytopenia can follow HIV seroconversion, resulting in intracranial hemorrhage [15]. During the course of AIDS, thrombocytopenia may result from thrombotic thrombocytopenic purpura or disseminated intravascular coagulation [16]. Hemorrhagic infarcts are reported to be less frequent than nonhemorrhagic infarcts, but when they do occur, it is usually in association with thrombocytopenia [4]. Other mechanisms of coagulopathy that may be associated with HIV infection include increased susceptibility to protein S deficiency [10] and antiphospholipid antibodies, including anticardiolipin antibodies [17]. In the absence of an identifiable cause of stroke, vasculitis may be an important etiology for cerebral infarction in AIDS patients [2, 3, 11, 18]. Different types have been described in the literature, including eosinophilic vasculitis, granulomatous angiitis and necrotizing vasculitis [19– 21]. Other mechanisms may also be responsible for this association. Increased deposition of circulating immune complexes is known to occur frequently in AIDS [11, 22, 23]. In addition, HIV may indirectly mediate vascular injury by the reaction of elastases from repeated infections, leading to disruption of the elastic lamina [24]. Another possible mechanism is the toxic effect of the HIV on vascular endothelium. Philippet et al. [2] found dilation and thrombosis of major cerebral arteries in two children with HIV infection resembling a vasculitis. Supporting this hypothesis, a major HIV transmembrane glycoprotein, gp41, has been found in the walls of such aneurysmal arteries of the circle of Willis [4, 25], but others have failed to detect gp41 in similar lesions [26]. Finally, other unusual causes of strokes not directly associated with HIV infection, such as sickle cell disease, moyamoya disease or syndrome, homocystinuria and mitochondrial cytopathies such as mitochondrial encephalopathy, lactic acidosis and stroke-like episodes, should be included in the differential diagnosis. Fig. 2. Anterior-posterior (a) and lateral (b) angiogram with left common carotid injection, showing complete occlusion of the left MCA and dilatation of the left internal carotid artery just proximal to the origin of the ophthalmic artery extending to the proximal left ACA. Note the collateral flow with some hypertrophied small vessels fed by the distal ACA and the posterior cerebral artery via the posterior communicating artery. 160 Pediatr Neurosurg 2002;37:158–163 Narayan/Samuels/Barrow Fig. 3. Diffusion-weighted MRI (a) and MRA (b) obtained 3 weeks after the initial angiogram showing a new large left frontal lobe infarction and occlusion of both ACAs not present on the initial angiogram. Stroke and Pediatric HIV Infection Pediatr Neurosurg 2002;37:158–163 161 Table 1. Review of the literature: HIV infection and stroke in pediatric patients Author Year Type of study Cases Type of stroke Imaging/pathological characteristics Presumptive etiology Comments Cho et al. [28] 1987 autopsy study 4 CI (4) HIV (4) two adults included in this report Frank et al. [30] 1989 case report 1 CI (1) VZV, HIV (1) – Park et al. [4] 1990 case series 7 CI (5) ICH (1) intimal proliferation of leptomeningeal vessels (4) HIV encephalitis (3) aneurysmal dilatation and vascular thickening (1) aneurysmal dilatation (1) arteriopathy (1) SNE (2) Kugler et al. [29] 1991 case report 1 CI (1) HIV (4) VZV, HIV (1) lymphoma, IT, HIV (1) IT, HIV (1) HIV (1) all ICH in patients with immune thrombocytopenia; 2 children with cardiomyopathy and SNE – Philippet et al. [2] 1994 case series 4 CI (4) ICH (1) Moriarty et al. [3] Fulmer et al. [30] 1994 1998 case series case series 3 2 Visudtibhan et al. [8] 1999 case series 2 Present study 2002 case report 1 CI (3) CI (1) SAH (1) CI (1) ICH (1) ICH (1) cortical gyral enhancement and basal ganglia calcifications on CT, SPECT abnormalities (1) aneurysmal dilatation and HIV (4) thrombosis (2) thrombosis (1) focal necrosis (1) thrombosis (1) HIV (3) aneurysmal dilatation (2) HIV (1) VZV, HIV (1) Arterial narrowing (2) HIV (2) aneurysmal dilatation and thrombosis (1) HIV (1) history of frequent infections in the 2 patients with aneurysmal dilatation and thrombosis – Stroke and seizure were initial presentation of HIV infection – Number in parentheses represent the number of cases. CI = Cerebral infarction; ICH = intracerebral hemorrhage; SAH = subarachnoid hemorrhage; SNE = subacute necrotizing encephalopathy; VZV = varicella-zoster virus; IT = immune thrombocytopenia; SPECT = single-photon emission computed tomography. HIV-positive patients presenting with a stroke should undergo an exhaustive workup including tests to rule out cardiac, infectious or immunological etiologies and coagulopathy. A cerebral angiogram or MRA may be indicated if there is evidence of an infarction or hemorrhage on CT or MRI. Regional cerebral blood flow techniques may be useful to demonstrate appropriate reduction in cerebral blood flow and reduction of cerebrovascular reserve with acetazolamide challenge to identify candidates for a bypass procedure. The effectiveness of medical therapy such as corticosteroids, vasodilators, low-molecular-weight dextran, antiplatelet agents and anticoagulants in the setting of HIVassociated vasculopathy is unproven. Also, the use of neuroprotective agents such as adenosine in the treatment of stroke has been questioned [27]. Patients with angiographically proven moyamoya-like patterns refractory to medical therapy may benefit from bypass procedures. The patient in this report had a known history of AIDS and presented with new-onset seizures and hemiparesis. Imaging studies confirmed cerebral infarctions in the anterior cerebral artery (ACA) and MCA distribution. The angiographic characteristics at the circle of Willis sug- 162 Pediatr Neurosurg 2002;37:158–163 gested an occlusive vasculopathy with development of moyamoya-like collateral vessels. There was no clinical or radiological evidence of infection, CNS malignancy or vascular malformations. The workup for other causes of stroke such as coagulopathy, hypercoagulable states or sources of cardio-emboli were negative. 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