Intracranial Arteriopathy Research Articles

Arterial Spin Labeling Perfusion MRI in Children and Young Adults with Previous Ischemic Stroke and Unilateral Intracranial Arteriopathy

Background: Little is known about cerebral blood flow (CBF) in young patients with ischemic stroke caused by an intracranial arteriopathy. Arterial spin labeling (ASL) perfusion is a noninvasive technique for measuring CBF. We aimed to investigate whether, in young patients with unilateral intracranial arteriopathy and previous ischemic stroke, CBF is compromised in noninfarcted brain areas of the symptomatic hemisphere and whether this is related to the severity of the arteriopathy. Methods: Patients aged 5-50 years, with previous middle cerebral artery (MCA) territory infarction and a unilateral intracranial arteriopathy, underwent magnetic resonance imaging (MRI), MR angiography and pseudocontinuous ASL perfusion MRI. We assessed the severity of stenosis of arteries that fed the symptomatic MCA territory, quantified CBF in the noninfarcted cortex of both MCA territories and generated CBF maps for visual CBF interpretation. Results: A total of 17 patients were included (median age 29 years, range 5-49, 29% male). We found a similar median quantified CBF in the symptomatic and asymptomatic MCA territories (86 ml·100 g^-1·min^-1). CBF maps showed hypoperfusion in the symptomatic MCA territory in 59% of patients compared to 18% based on quantified CBF. Patients with a severe arteriopathy more often showed hypoperfusion on CBF maps than patients with a mild arteriopathy. In 53% of patients, small foci of increased signal intensity were visible on CBF maps around an area of hypoperfusion, indicating vascular artifacts. In these patients, we found large intraindividual variation in the quantified CBF in the symptomatic hemisphere. In 47% of patients, the visual interpretation of perfusion did not correspond with the quantified CBF. Conclusions: This study shows that more than half of young patients with previous ischemic stroke in the MCA territory and a unilateral intracranial arteriopathy have hypoperfusion in the noninfarcted cortex of the symptomatic hemisphere when CBF is visually assessed using a CBF map, in particular in patients with a severe arteriopathy. In the same patients, quantification of CBF shows hypoperfusion in the symptomatic hemisphere in only 18%. This discrepancy is caused by labeled blood within the arteries that has not yet reached the tissue at the time of imaging. Visual assessment can show hypoperfusion, while the quantified CBF in a similar region appears higher when the intravascular labeled blood is included in the region of interest. Further research should focus on elucidating whether cerebral perfusion deficits in young stroke patients with intracranial arteriopathy might help to identify patients who are at risk of poor outcome or stroke recurrence.

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

How should propranolol be initiated for infantile hemangiomas: Inpatient versus outpatient?

Recent Advances in Moyamoya Disease: Pathophysiology and Treatment

Moyamoya disease is a progressive intracranial arteriopathy characterized by bilateral stenosis of the distal portion of the internal carotid artery and the proximal anterior and middle cerebral arteries, resulting in transient ischemic attacks or strokes. The pathogenesis of moyamoya disease remains unresolved, but recent advances have suggested exciting new insights into a genetic contribution as well as into other pathophysiological mechanisms. Treatment that may halt progression of the disease or even reverse the intracranial arteriopathy is yet to be found. There are strong indications that neurosurgical intervention, through direct, indirect, or combined revascularization surgery, can reduce the risk of ischemic stroke and possibly also cognitive dysfunction by improving cerebral perfusion, although randomized clinical trials have not been performed. Many questions regarding the indication for and timing of surgery remain unanswered. In this review, we discuss recent developments in the pathogenesis and treatment of moyamoya disease.

Intracranial Arteriopathy in Tuberous Sclerosis Complex

Arterial aneurysms, mostly aortic and intracranial, have been occasionally reported in patients with tuberous sclerosis complex. Brain magnetic resonance imaging reports of 404 patients with definite and 16 patients with either probable or possible tuberous sclerosis complex were revised for intracranial aneurysms. Among these patients, brain images of 220 patients with definite and 16 with probable or possible tuberous sclerosis complex were reviewed. Intracranial aneurysms were reported in 3 of 404 patients with a definite diagnosis (0.74%) (general population: 0.35%), including 2 children. A fourth intracranial aneurysm was found in a patient with probable tuberous sclerosis complex, who did not have tubers or subependymal nodules but had clinical manifestations related to neural crest derivatives, including lymphangioleiomyomatosis and extrarenal angiomyolipomas. The authors hypothesize that neural crest dysfunction can have a major role in intracranial arteriopathy in tuberous sclerosis complex, as smooth muscle cells in the forebrain vessels are of neural crest origin.

Moving Vessel Wall Research Beyond the Plaque

The overlap between atherosclerotic disease of the cerebrovascular, cardiovascular, and peripheral vasculature has long been recognized. Carotid atherosclerosis increases the odds of coronary events1 and of finding atherosclerotic changes in coronary, cerebral, aortic, and iliac arteries.2 Similarly, peripheral vascular disease is a risk factor for both stroke and myocardial infarction and is associated with extracranial carotid and intracranial atherosclerosis.3,4 Data from the Reduction of Atherothrombosis for Continued Health (REACH) registry show that atherosclerosis in 1 vascular bed increases the risk of adverse outcomes in each of the other locations, and that multiple disease locations at baseline increase the risk of subsequent cardiovascular and cerebrovascular events.5 Given shared underlying risk factors and pathophysiology, it is not surprising that those who present with atherosclerotic disease in 1 vascular bed are at increased risk for disease in others.6 See accompanying article on page 2240 It is fair to say that although considerable attention has been given to atherosclerotic disease affecting peripheral, cardiac, and carotid arteries, important gaps remain in our knowledge. For example, the intracranial circulation has received comparatively …

Abstract WP408: Patent Foramen Ovale in Childhood Arterial Ischemic Stroke: Prevalence and Stroke Recurrence in a Prospective Cohort

Background and Objectives: The role of patent foramen ovale (PFO) in childhood arterial ischemic stroke (AIS) is poorly understood. We aimed to define the prevalence of PFO in children with first AIS, and its relationship to recurrence. Methods: Subjects (>28 days to <18 years) with AIS between 2006-2012 were identified from a single-center consecutive prospective cohort study. Subjects were excluded with diagnoses of congenital or acquired heart disease, moyamoya, meningitis, brain tumor, surgery of the head or neck, endovascular procedures, metabolic disorder, or hemoglobinopathy. Charts were abstracted for clinical and radiologic features, echocardiogram, and thrombophilia evaluations. Recurrent events included 1) stroke, defined as a new focal deficit with new infarction on imaging, or 2) transient ischemic event (TIA). Incidence of recurrence in children with PFO was compared to those without PFO by survival analysis. Data are given as median (range). Results: Forty-four subjects met eligibility criteria, median age 5.8 years (0.1-17), 77% male. Echocardiogram was obtained in 42 (95%), and disclosed a PFO in 7/42 (17%), of which other stroke risk factors were present in 5. In the entire cohort, primary stroke risk factors other than PFO included cervical arterial dissection (8), intracranial focal cerebral arteriopathy (8), thrombophilia (10), CNS vasculitis (1), other (4), none (11). All subjects received antithrombotic treatment for stroke prevention, and 2 underwent endovascular PFO device closure. Follow-up was available in all subjects at median of 25 months (4-71). Incidence rate of recurrent stroke or TIA was 8/1000 - person-months, and was similar in both groups, affecting 1/7 subjects with PFO at 0.3 months, and in 6/37 subjects without PFO at median of 2.8 months (0.3-36) after first stroke. Conclusions: PFO is present in a small proportion of children with first AIS, often with other risk factors. Recurrence in children with PFO in this small cohort was similar to those without PFO. Outcomes may have been influenced by other stroke risk factors, and secondary stroke preventive treatments including PFO closure and antithrombotic treatment. The role of PFO in initial and recurrent stroke remains uncertain, and deserves further study.

Imaging Characteristics of Cerebrovascular Arteriopathy and Stroke in Hutchinson-Gilford Progeria Syndrome

HGPS is a rare disorder of segmental aging, with early morbidity from cardiovascular and cerebrovascular disease. The goal of this study was to identify the neurovascular features, infarct type, topography, and natural history of stroke in the only neurovascular imaging cohort study of HGPS. We studied 25 children with confirmed diagnoses of HGPS and neuroimaging studies available for review. Relevant clinical information was abstracted from medical records. We identified features suggestive of a vasculopathy unique to HGPS, including distinctive intracranial steno-occlusive arterial lesions, basal cistern collateral vessels, and slow compensatory collateral flow over the cerebral convexities. The arterial pathology in the neck consisted of distal vertebral artery stenosis with prominent collateral vessel formation as well as stenosis and calcification of both the cervical internal and common carotid arteries. Radiographic evidence of infarction was found in 60% of patients, of which half were likely clinically silent. Both large- and small-vessel disease was observed, characterized by arterial territorial, white matter, lacunar, and watershed infarcts. We report a unique intracranial and superior cervical arteriopathy in HGPS distinct from other vasculopathies of childhood, such as Moyamoya, and cerebrovascular disease of aging, including atherosclerosis. Arterial features of the mid and lower neck are less distinctive. For the first time, we identified early and clinically silent strokes as a prevalent disease characteristic in HGPS. Longitudinal analysis of stroke incidence and vasculopathy may provide an outcome measure for future treatment interventions for children with HGPS.

Prevalence of Extracranial Internal Carotid Arteriopathy in Stroke-Free SCA-Children: A New Risk Factor for Silent Strokes

Abstract 88▪▪This icon denotes a clinically relevant abstract Background.Strokes are a well-known complication of sickle-cell anemia (SCA), and are largely due to intracranial arteriopathy, detected by routine transcranial Doppler (TCD). Adams et al. showed in the STOP I trial (N Engl J Med, 1998) the efficiency of transfusion programs for primary stroke prevention in patients identified by TCD as being at risk of stroke. We recently reported in the CHIC newborn cohort (Bernaudin et al., Blood, 2011) that early TCD imaging (TCDI) screening significantly reduces the risk of stroke by age 18 from the previously reported 11% to only 1.9%, but has not allowed adequate prevention of silent infarcts, with a risk of 37.1% by age 14, suggesting that TCDI does not distinguish all SCA-patients at risk of silent infarcts. Extracranial internal carotid artery (eICA) vasculopathy is considered rare and has not been routinely assessed; however, several recent cases of stroke with extracranial arteriopathy prompted the inclusion of eICA evaluation in routine screening. The aim of the study was to establish the ranges of eICA velocities in SCA-patients, to determine the cut-off limits of velocities predictive of eICA stenoses by extracranial MRA, to evaluate the prevalence of abnormal eICA velocities and to determine their association with intracranial stenoses and/or silent infarcts by MRI. Methods.Since June-2011, all stroke-free SCA patients from the CHIC and Debre cohorts who had routine yearly TCDI for intracranial arteries were also systematically assessed for eICA using submandibular windows (Gorman et al., Neurology 2009) and the same 2Mhz TCDI transducer probe. Time-averaged mean of maximum velocities (TAMMV) were obtained for intra and extracranial cerebral arteries. By color Doppler mapping, the course of eICA was considered as straight, or as tortuous if the artery changed direction with an angle > 120° between adjacent segments. Extracranial cervical MRA was added to routine intracranial MRI/MRA, performed every 2 years or as soon as abnormal velocities were found. Results.Between June 2011 and January 2012, 435 consecutive SCA-children from the two cohorts (202M, 233F) were assessed by Doppler at the median age of 8.5 years (range: 1.3–18.7). MRI/intra and extracranial MRA was performed in 104 patients. At time of Doppler assessment, mean±SD hemoglobin was 9.1±1.6 g/dl. eICA velocities were significantly correlated with middle cerebral arteries (MCA) velocities (r=0.234, p<0.001), and were about 25–30% lower than MCA velocities (mean:95±38 vs 127±32 cm/sec). As for MCA, eICA velocities were maxima between 3–7 years of age. eICA tortuosities were echo-detected in 25% cases (107/435), and were more frequent in boys (65/202; 32%) than in girls (42/233; 18%), p<0.001. Regression logistic analysis showed that tortuosities were not associated with age, but significantly associated with males (OR:2.2, 95%CI:1.4–3.4, p=0.001). Cervical MRA found stenoses in 40/104 patients. ROC curve showed that eICA velocities ≥ 160 cm/sec were highly predictive of stenoses on eMRA (100% specificity, 80% sensitivity). The prevalence of eICA velocities ≥ 160 cm/sec was 10.3% (45/435), and was significantly higher in males (14.9% vs 6.4%; p=0.004). Low hemoglobin (OR:2.6/1g/dl decrease, 95%CI:1.4–4.6; p=0.002) and tortuosities (OR:14.5, 95%CI:4.1–50; p<0.001) were significant and independent risk factors for eICA velocities ≥ 160cm/sec. Intracranial stenoses were detected in 29/104 patients, while 40/104 patients had extracranial stenoses with 31/40 showing no intracranial stenoses. Silent infarcts were detected in 35/104 patients, and were highly associated with the presence of intra and/or extracranial stenoses (30/35: 86%, p<0.001). Intra (OR:5.1,95% CI:1.9–13.8, p=0.002) and extracranial (OR:4.5, 95% CI:1.7–11.6; p=0.002) stenoses were significant and independent risk factors for silent infarcts. Conclusion.This study shows for the first time that in cohorts previously assessed early by TCDI for intracranial arteries, about 10% stroke-free patients have eICA vasculopathy. Moreover, we show that intra and/or extracranial stenoses are significant risk factors for silent infarcts. These data may explain why silent infarcts still occurred in patients early assessed by TCDI exploring only intracranial arteries. Thus, extracranial Doppler assessment should be routinely done with TCD to evaluate the full extent of cerebral vasculopathy in SCA. Disclosures:No relevant conflicts of interest to declare.

The Course of Unilateral Intracranial Arteriopathy in Young Adults With Arterial Ischemic Stroke

Unilateral intracranial focal nonprogressive arteriopathy is often found in children with arterial ischemic stroke. We aimed to investigate the course of unilateral intracranial arteriopathy in young adults. We searched the Utrecht Stroke Database for patients between 16 and 50 years of age diagnosed with anterior circulation arterial ischemic stroke and a nonatherosclerotic, unilateral intracranial large-artery arteriopathy between 1991 and 2005. We assessed clinical features, potential causes, risk factors, extent of infarction and arteriopathy at presentation, long-term angiographic course, and clinical outcome. Of 356 patients with anterior circulation arterial ischemic stroke, 17 (5%) had a documented unilateral intracranial arteriopathy, of whom 14 could be included for follow-up investigations (median age, 34 years; range, 27-49 years). Median duration of follow-up was 8.8 years (range, 1.7-12.8 years). In 11 patients, onset of symptoms was not abrupt. The arteriopathy normalized completely in 5 and improved in 3 patients; in none of the patients did the arteriopathy worsen. Two of 14 patients had recurrent symptoms. Ten patients (71%) had a good outcome (modified Rankin Scale score≤2). In young adults, arterial ischemic stroke is rarely caused by a unilateral intracranial arteriopathy. Similar to children, onset of symptoms in young adults is often not abrupt and the arteriopathy may improve over time. Late recurrences were rare. Possibly, a monophasic inflammatory process, as has been suggested for childhood intracranial focal nonprogressive arteriopathies, also occurs in young adults.

Editorial: Pediatric moyamoya

The evidence-based practice guidelines for moyamoya disease (MMD) proposed by Drs. Smith and Scott,1 who are world-leading scholars in the field, are a wellsummarized reference for doctors managing the treatment of patients with MMD, especially in areas in which MMD is not prevalent. These investigators have created a framework that can be modified as knowledge and experience are accumulated in the field of basic research as well as clinical practice. Among many pertinent issues, I would like to comment on some points of controversy and future directions. The differential diagnosis of MMD should be made cautiously, especially in areas in which this disorder is rather common. Some of the vascular inflammatory diseases or intracranial arteriopathy may mimic the clinical features of MMD. In Asian countries, unilateral stenosis of the middle cerebral artery with faint collateral channels at the base of the brain is common. Occlusion of the M1 portion with basal ganglia infarction seems to be a different entity, with spontaneous improvement and no progression of disease as is observed in MMD. Moyamoya disease progresses rapidly in children younger than 3 years. It frequently manifests with stroke, without preceding transient ischemic symptoms. These patients are prone to bilateral widespread infarction if management is delayed. In these cases, screening is an important issue. Unfortunately, however, although MMD shows genetic and racial predisposition, genetic screening is still not possible. Screening with MRI studies for family members of patients with MMD may be helpful. Nonetheless, the rate of progression in young children is so fast that a single MRI examination cannot predict the occurrence of disease during the period of high-risk, MMD-induced wide infarction. Genetic and molecular research will be crucial for the protection of these young children. The management of ischemia in children with MMD by revascularization surgery, whether it is direct, indirect, or combined, cannot be investigated by a randomized clinical trial because this approach would be unethical. On the other hand, surgery has not been widely accepted in cases with bleeding, due to the lack of solid evidence. There are controversies regarding the use of aspirin or anticoagulation therapy, except with respect to perioperative use for direct revascularization surgery. The main primary pathology, fibromuscular intimal hyperplasia, also raises questions about the long-term use of aspirin or anticoagulation therapy. Keeping physiological factors such as body temperature, circulation volume, hemoglobin level, and blood levels of O2 and CO2 within the safe ranges is most important to avoid perioperative ischemic complications. Anesthesia with hyperventilation, as is preferred in most brain operations, is highly dangerous in MMD, but this caveat is sometimes neglected in the institutes in which MMD operations are seldom performed. Postoperative crying and agitation should be controlled. The scalp tissue in children is thin, and the wellvascularized layers are detached and inserted into the intracranial cavity in indirect revascularization surgery. The remaining, less vascularized thin layers with defective underlying tissue are vulnerable to necrosis. Great care should be taken when handling scalp tissue in young children. Improvement of the ischemic symptoms is rapid, and it occurs not in a matter of months, but rather of weeks. The duration of the hospital stay or perioperative treatment with hydration, anticonvulsants, and so on should be decided based on the usual and unusual early postoperative course of MMD. Postoperative headache or ischemic symptoms are not rare. Although the revascularization surgery improves the hemodynamic status of the brain, it does not halt the progression of MMD itself. The progression of arterial stenosis may lead to the progressive dilation of collateral channels and may cause headache. The headache has several characteristics. A bothersome headache can be relieved by additional revascularization surgery. Young patients or patients with long-term follow-up often exhibit recurrent ischemic symptoms or infarction. Protocols for long-term follow-up with cost-benefit efficiency and strategies for additional surgery will be helpful. These guidelines will probably be widened in scope, including different management strategies according to the following factors: age of the patient; asymptomatic presentation; patients with bleeding; patients with pregnancy and hyperthyroidism; and patients with postoperative headache, progressive ischemia, and different followup protocols. Continuous refinement of the contents of these guidelines will be necessary in the future. The work presented here represents an excellent jumping-off point for future efforts. (http://thejns.org/doi/abs/10.3171/2011.10.PEDS11467) 351 352

Spontaneous Post-Partum Cervical Carotid Artery Dissection in a Patient with Reversible Cerebral Vasoconstriction Syndrome

Post-partum cervicocephalic artery dissection (pp-CAD) is a rare and poorly understood condition. To our knowledge, only 21 cases have been reported. Reversible cerebral segmental vasoconstriction (RCSV) was first described by Call and Fleming in 1988, and its association with pp-CAD has only been reported in three cases. However, in those cases it is unclear whether the pp-CAD may have been caused by straining during labor and therefore merely coincidental to the intracranial arteriopathy. We describe a 41-year-old right-handed African-American woman who developed the syndrome of pp-CAD (headaches, trace subarachnoid hemorrhage and diffuse cerebral arteriopathy on angiogram) two weeks after delivery. In this unique case, the patient had fortuitously undergone an MR study twice over a four day period which included the carotid bifurcations. During that time the patient was an inpatient, on bed rest and subject to continuous cardiac monitoring. The interval studies documented a true spontaneous right internal carotid artery dissection occurring without obvious cause. The patient had noted moderate right neck pain developing between the two MR studies but experienced no neurological deficits. Subsequent conventional angiography confirmed the presence of postpartum cerebral arteriopathy and the cervical dissection. The patient was managed conservatively with antiplatelet medication and had an otherwise uneventful course. We hypothesize whether transient arterial wall abnormalities, postpartum hormonal changes or subtle connective tissue aberrations play a similar role in the pathogenesis of these two associated conditions.

Craniocervical arterial dissection in children: diagnosis and treatment.

Diagnosis of craniocervical arterial dissection (CCAD) in children begins with a careful history and physical in a child with a transient ischemic attack (TIA) or arterial ischemic stroke (AIS). The extent of radiologic evaluation for suspected CCAD is based upon careful consideration of the risks associated with the best imaging techniques, weighed against the benefits of enhanced vascular imaging with better diagnostic sensitivity. Although conventional angiography (CA) and CT angiography (CTA) have a higher sensitivity than magnetic resonance angiography (MRA), they are accompanied by risks: for CA, femoral hematoma, femoral arterial pseudoaneurysm, recurrent AIS, and radiation exposure; for CTA, radiation. For children (non-neonates) with suspected CCAD, MRI with MRA is recommended as the first-line imaging study. MRI usually includes diffusion-weighted, FLAIR, and T1 images of the brain, and T1 or T2 fat-saturation axial imaging through the neck. MRA should include 3D time-of-flight MRA of the head and neck (from the aortic arch through the circle of Willis). Contrast-enhanced MRA should be highly considered in neck imaging. If MRI/MRA is equivocal, CCAD is strongly suspected but not detected on MRI/MRA (especially in the posterior circulation), or the child has recurrent events, additional imaging of the craniocervical vasculature is likely warranted. Individual clinical circumstances warrant careful, case-by-case consideration. Treatment of CCAD in children is challenging and differs for intracranial and extracranial dissections. In extracranial CCAD, we most commonly use anticoagulation for 6weeks to 6months in patients with TIA or AIS. Typically, unfractionated heparin is used in the acutely ill patient at heightened risk for bleeding (because of its short half-life), whereas low-molecular-weight heparin (LMWH) or warfarin are reserved for the stable patient. If the history is suspicious for dissection (head and neck trauma, recent cervical chiropractic manipulation, recent car accident, or neck pain), we consider treatment for dissection even with normal MRI/MRA. For patients with CCAD with a stroke size greater than one third to one half of the middle cerebral artery territory (or other bleeding risk factors) and extracranial CCAD, in whom there is concern about heightened risk for hemorrhagic conversion, we commonly use aspirin therapy during the acute phase. Regardless of their treatment in the initial weeks to months, we subsequently treat all patients with aspirin for 1year after their event, and sometimes longer if they have other risk factors. Interventional techniques, such as extracranial cerebral arterial stent placement or selective occlusion, are understudied in children. Interventional techniques are typically reserved for patients who fail aggressive medical management and have recurrent TIA or AIS. The diagnosis and treatment of intracranial dissection is extraordinarily challenging in children, in whom inflammatory intracranial arteriopathies are common. When intracranial arteriopathy is clearly associated with dissection, the clinician should look for the presence of subarachnoid hemorrhage and/or dissecting aneurysm. Treatment decisions should be made by a multidisciplinary pediatric stroke team, given the lack of data in this area. Intracranial cerebral artery stent placement carries high risk and is not recommended for intracranial CCAD in children. Most importantly, we educate all children with CCAD and their parents about the paucity of evidence in the treatment of this disease, the risks of enhanced imaging techniques such as CTA or CA, and the challenges involved in weighing the risks of aggressive therapies and interventions against the costs of unclear diagnosis and potentially ineffective treatments. We also educate our patients with CCAD about the signs and symptoms of recurrence and the importance of emergent evaluation.

E-007 Spontaneous post-partum cervical carotid artery dissection in a patient with reversible cerebral vasoconstriction syndrome

Postpartum cervicocephalic artery dissection (pp-CAD) is a rare and poorly understood condition. To our knowledge, only 21 cases have been reported. Reversible cerebral segmental vasoconstriction was first described by Call...

Diagnostic challenges in RCVS, PACNS, and other cerebral arteriopathies

In the field of vascular neurology, few conditions pose greater diagnostic and therapeutic challenges than the intracranial cerebral arteriopathies (Table 1). They are a common cause of secondary headaches (vascular headaches), and perhaps the most common cause of stroke, accounting for 20–35% of strokes in young adults (1–2) and over 50% in children (3). In older adults, intracranial atherosclerosis alone accounts for 10–50% of stroke (4), and lipohyalinotic small-vessel disease another 15%. Intracranial arteriopathies can be classified according to etiology or the affected age group. From the diagnostic standpoint it is convenient to classify them according to the size of the affected artery as medium-vessel or small-vessel; the former induce abnormalities visible on transfemoral angiography, whereas the latter affect distal small vessels that are beyond the current resolution of angiography. Some arteriopathies, such as the reversible cerebral vasoconstriction syndromes (RCVS) and primary angiitis of the central nervous system (PACNS), can affect both the medium and the small vessels. The diagnosis of small-vessel cerebral arteriopathies requires a high level of clinical suspicion, astute interpretation of imaging findings, and a detailed examination of the skin, eye, or other organ systems. They are often disclosed by the presence of recurrent small-vessel infarcts in patients with chronic headaches, skin lesions, known systemic infections, or MRI findings of scattered small-vessel infarcts or micro-hemorrhages with or without white matter lesions. Several small-vessel arteriopathies (e.g. CADASIL (5); see Table 1) have established diagnostic criteria or can be confirmed with specialized tests, such as skin or brain biopsy, or genetic, immunological, or microbiological tests. Some small-vessel arteriopathies can be comfortably diagnosed with clinical-imaging correlation, for example lipohyalinotic small-vessel disease in patients with chronic hypertension, a lacunar stroke syndrome, and a corresponding small cerebral infarction in the distribution of a ‘penetrator’ artery. Others such as PACNS continue to pose diagnostic challenges because definitive diagnostic tests such as brain biopsy are often false-negative, and tests such as cerebrospinal fluid examination and angiography have low specificity (6). Medium-vessel cerebral arteriopathies are typically disclosed when CTor MRangiography, performed during the routine evaluation of stroke or headache, reveal arterial irregularities. Alternately, they are suggested by clinical clues such as recurrent thunderclap headaches; stroke in the setting of recent headache, infection, stereotyped transient ischemic attacks, recent pregnancy, or illicit drug use; or imaging findings of unilateral deep border zone infarcts (7). Once arterial irregularity is documented, it becomes imperative to determine the etiology in order to initiate appropriate therapy. Unfortunately, in the absence of validated diagnostic criteria or confirmatory tests for most medium-sized arteriopathies, the approach remains variable and uncertain. Older adults are usually assumed to have intracranial atherosclerosis if they have vascular risk factors or calcified proximal cerebral arteries. In children, the diagnosis is particularly challenging given the need for serial angiography or advanced imaging (e.g. 3-Tesla MRI) to diagnose conditions such as transient cerebral arteriopathy and intracranial dissection that are more common in childhood. Young adults with intracranial arterial irregularities typically undergo a battery of expensive diagnostic tests, most of which have relatively low sensitivity and specificity, often culminating in a brain biopsy or empirical treatment for cerebral ‘vasculitis’, which is not without risks. Linn et al. (8) report a study of nine patients with headache, variable clinical deficits, and a mediumvessel cerebral arteriopathy, who developed clinical

O3-1 Nocturnal oxyhemoglobin desaturation, reticulocytosis and intracranial arteriopathy in children with sickle cell disease

O3-1 Nocturnal oxyhemoglobin desaturation, reticulocytosis and intracranial arteriopathy in children with sickle cell disease

O3-4 The incidence of childhood stroke

Arteriopathy on MRA was graded as 0 (none), or as increasing severity grades 1, 2 or 3, by two radiologists blinded to the other data. Results: Despite no significant differences across the degrees of arteriopathy in genotype or hemoglobin, mean overnight SpO2 was higher (p< 0.01) in those with grade 0 (97.0±1.6%) than those with grades 2 (93.9±3.7%) or 3 (93.5±3.0%) arteriopathy (abnormal MRA). Reticulocyte count was lower (p< 0.01) in those with grade 0 (187±136*109/L) than those with grades 1 (466±322*109/L), 2 (450±239*109/L) and 3 (624±293*109/L) arteriopathy. In logistic regression, lower mean overnight SpO2 (Odds ratio 0.51, 95% confidence intervals, CI, 0.32 0.81; p< 0.01) predicted abnormal MRA. Higher reticulocyte count (Odds ratio 1.011, 95%CI 1.005 1.018; p< 0.01) was negatively correlated with mean overnight SpO2 and independently predicted abnormal MRA in a multivariable model, with a trend for an effect of lower mean overnight SpO2. Conclusion: Low nocturnal SpO2 and reticulocytosis are associated with intracranial arteriopathy on MRA in children with SCD. Preventative strategies might reduce stroke risk.

O3-2 Predictors of intracranial hypertension in acute encephalopathies

Arteriopathy on MRA was graded as 0 (none), or as increasing severity grades 1, 2 or 3, by two radiologists blinded to the other data. Results: Despite no significant differences across the degrees of arteriopathy in genotype or hemoglobin, mean overnight SpO2 was higher (p< 0.01) in those with grade 0 (97.0±1.6%) than those with grades 2 (93.9±3.7%) or 3 (93.5±3.0%) arteriopathy (abnormal MRA). Reticulocyte count was lower (p< 0.01) in those with grade 0 (187±136*109/L) than those with grades 1 (466±322*109/L), 2 (450±239*109/L) and 3 (624±293*109/L) arteriopathy. In logistic regression, lower mean overnight SpO2 (Odds ratio 0.51, 95% confidence intervals, CI, 0.32 0.81; p< 0.01) predicted abnormal MRA. Higher reticulocyte count (Odds ratio 1.011, 95%CI 1.005 1.018; p< 0.01) was negatively correlated with mean overnight SpO2 and independently predicted abnormal MRA in a multivariable model, with a trend for an effect of lower mean overnight SpO2. Conclusion: Low nocturnal SpO2 and reticulocytosis are associated with intracranial arteriopathy on MRA in children with SCD. Preventative strategies might reduce stroke risk.

Intracranial Arteriopathy and Ischemic Stroke

Repeated vascular imaging findings and clinical charts of 79 children with anterior circulation arterial ischemic stroke (AIS) and unilateral intracranial arteriopathy of the internal carotid bifurcation were studied at the University Medical Center, Utrecht, The Netherlands, and other centers in France, UK, and Canada.

The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke

Arteriopathies are the commonest cause of arterial ischaemic stroke (AIS) in children. Repeated vascular imaging in children with AIS demonstrated the existence of a ‘transient cerebral arteriopathy’ (TCA), characterized by lenticulostriate infarction due to non-progressive unilateral arterial disease affecting the supraclinoid internal carotid artery and its proximal branches. To further characterize the course of childhood arteriopathies, and to differentiate TCA from progressive arterial disease, we studied the long-term evolution of unilateral anterior circulation arteriopathy, and explored predictors of stroke outcome and recurrence. From three consecutive cohorts in London, Paris and Utrecht, we reviewed radiological studies and clinical charts of 79 previously healthy children with anterior circulation AIS and unilateral intracranial arteriopathy of the internal carotid bifurcation, who underwent repeated vascular imaging. The long-term evolution of arteriopathy was classified as progressive or TCA. Clinical and imaging characteristics were compared between both groups. Logistic regression modelling was used to determine possible predictors of the course of arteriopathy, functional outcome and recurrence. After a median follow-up of 1.4 years, 5 of 79 children (6%) had progressive arteriopathy, with increasing unilateral disease or bilateral involvement. In the others (94%), the course of arteriopathy was classified as TCA. In 23% of TCA patients, follow-up vascular imaging showed complete normalization, the remaining 77% had residual arterial abnormalities, with improvement in 45% and stabilization in 32%. Stroke was preceded by chickenpox in 44% of TCA patients, and in none of the patients with progressive arteriopathies. Most infarcts were localized in the basal ganglia. In 14 (19%) of TCA patients, transient worsening of the arterial lesion was demonstrated before the arteriopathy stabilized or improved. Thirteen TCA patients (18%) had a recurrent stroke or TIA. Thirty TCA patients (41%) had a good neurological outcome, compared with none of the five patients with progressive arteriopathy. Arterial occlusion, moyamoya vessels and ACA involvement were more frequent in progressive arteriopathies. Cortical infarct localization was significantly associated with poor neurological outcome (OR 6.14, 95% CI 1.29–29.22, P = 0.02), while there was a trend for occlusive arterial disease to predict poor outcome (OR 3.00, 95% CI 0.98–9.23, P = 0.06). Progressive arteriopathy was associated with recurrence (OR 18.77, 95%CI 1.94–181.97, P = 0.01). The majority of childhood unilateral intracranial anterior circulation arteriopathies (94%) have a course that is consistent with TCA, in which transient worsening is common. Although the arterial inflammation probably causing TCA is ‘transient’, most children are left with permanent arterial abnormalities and residual neurological deficits.

Dilative arteriopathy and basilar artery dolichoectasia complicating late-onset Pompe disease

Strokes related to intracranial aneurysm or arteriopathy have been reported in a few patients with late-onset Pompe disease. These reports suggested that cerebral vessel involvement could be an underrecognized complication of this disease. We report cerebral artery involvement in three French patients with late-onset Pompe disease. The first patient died at age 35 years from complications of a giant fusiform aneurysm of the basilar artery, and her 34-year-old sister showed evidence of dolichoectatic basilar artery on magnetic resonance angiography. A dilative arteriopathy complicated with carotid artery dissection was diagnosed in the third patient, aged 50 years. Two patients are currently being treated with enzyme replacement therapy (alglucosidase alfa), and regular angiographic follow-up showed the absence of progression of vascular abnormalities in one of them. These observations, combined with previously reported cases, confirm that Pompe disease should be recognized as a predisposing condition to dilative arteriopathy and cerebral aneurysm formation, although the real incidence of these vascular complications remains unknown.