Focal Cerebral Arteriopathy of the Young: Clinical Profile, Outcomes, and Utility of High-Resolution Vessel Wall Imaging Open Access

Focal cerebral arteriopathy (FCA) refers to a unilateral focal irregularity or stenosis of a large intracranial artery of the anterior circulation that supplies the area of infarction [1‒3]. FCA could have a transient (nonprogressive stenosis) or a progressive course, determined primarily by follow-up angiography [1, 2]. Despite being widely reported in the pediatric literature, where it accounts for about 25% of pediatric stroke etiologies, description of adult cases is restricted to a few case series [4, 5]. Moreover, the utility of a high-resolution magnetic resonance vessel wall imaging (MRVWI) has not been explored in adult FCA patients. We aimed to describe the clinical profile of a cohort of young adults with focal cerebral arteriopathy and explore the role of high-resolution MRVWI in the diagnostic workup and outcome of these patients.

We retrospectively reviewed our electronic medical records of all young patients (aged 18–55 years) admitted to our institute with acute ischemic stroke between 2010 and 2022. We defined FCA as unilateral, unifocal, nonprogressive stenosis/irregularity of the distal internal carotid artery (ICA) or its proximal branches [3]. We excluded cases that had a clear alternative diagnosis, such as moyamoya disease, intracranial atherosclerosis, or reversible cerebral vasoconstriction syndrome. Data on clinical presentation, parenchymal imaging (CT brain or MRI brain), and vessel imaging (CT angiogram, MR TOF angiogram, or digital subtraction angiography) including a high-resolution MRVWI performed at presentation and during follow-up were reviewed. Vessel wall enhancement and grading of its intensity were done using previously published criteria [6]. FCA severity score (FCASS) was calculated for the initial and final angiograms [7]. Short-term and long-term outcomes were noted at 3-month and 1-year follow-ups, respectively, with poor outcome defined as a modified Rankin Scale (mRS) >2. Workup for alternative etiologies included antinuclear antibodies, anti-neutrophil and cytoplasmic antibodies, anti-double-stranded DNA antibody, anti-Ro and anti-L antibodies, serum venereal disease research laboratory test, viral serologies for human immunodeficiency virus, hepatitis B surface antigen, anti-hepatitis C antibodies, serum varicella antibodies, homocysteine levels, sickling test, hemoglobin electrophoresis, echocardiogram, and an electrocardiogram. Results of cerebrospinal fluid (CSF) were collected when available. The study was approved by the Institutional Ethics Committee (IEC). As it was a retrospective review, a waiver of informed consent was obtained from the IEC.

Between 2010 and 2022, we identified 295 young adults admitted with a first-ever stroke, of whom 17 satisfied the criteria for FCA. However, seven cases were excluded (progression of arteriopathy in subsequent imaging suggestive of unilateral moyamoya disease = 5, no clinical follow-up = 2). We thus included 10 patients (9 males) with focal cerebral arteriopathy, giving us an incidence rate of 2.8 cases per 1,000 person-years. The median age of the cohort was 28.5 (range 19–43) years. Vascular risk factors like hypertension, diabetes, and dyslipidemia were noted in four (40%) patients. The majority (90%) had an ischemic event at presentation, while 1 patient (10%) presented with headache and cortical subarachnoid hemorrhage. At the presentation, 5 patients had transient ischemic attacks (TIAs), three had minor strokes (median National Institute of Health Stroke Scale score [NIHSS] 2) and one had a major stroke with an NIHSS of 13.

Six patients underwent CT angiograms, and 8 patients underwent digital subtraction angiography at the time of admission, which ruled out the involvement of other vessels. The maximum luminal narrowing ranged from 50 to >95%. All 10 patients underwent MRVWI at initial admission. Nine (90%) patients had a characteristic involvement of the supraclinoid ICA with or without involvement of the proximal M1 middle cerebral artery (MCA) or A1 anterior cerebral artery (A1 ACA) (Table 1). Concentric and eccentric patterns of vessel wall enhancement were noted in 8 and 2 patients, respectively. The median length of vessel wall enhancement was 9 mm (range 2.8–16 mm), and most (80%) patients had a grade 2 enhancement. Six patients had a follow-up MRVWI with a reduction in grade of contrast enhancement noted in 3 patients (Fig. 1), and a reduction in length of enhancement (median 1.75 mm) was noted in 4 patients. The FCA severity score (FCASS) was obtained in all patients with a median of 8 (range 2–12) at initial imaging and a median of 7 (range 2–14) at follow-up imaging. In the entire cohort, only 2 patients had improvement in the focal stenosis (Fig. 2), while 8 patients had no change in their stenosis.

Serum varicella IgG was positive in 4/5 cases tested. Six of the 7 patients had a non-inflammatory CSF, while one had an isolated mild elevation of protein (64 mg/dL) without pleocytosis. All other workups for etiologies of young stroke were noncontributory in these patients.

All 9 patients with an ischemic presentation were treated with antiplatelets. Three patients received additional oral corticosteroids that were tapered gradually over 3–12 months, two of whom had reduction in vessel wall enhancement, while one had partial resolution of stenosis on follow-up. However, except for the patient with a major stroke who continued to remain at mRS 3, both at 3 months and 1 year, all other patients had recovered completely to mRS 0 by the time of discharge. The median follow-up duration was 2 (range 1–4) years, and there were no recurrences. There was no significant difference in short- or long-term outcomes between those who received steroids compared to those who did not. Similarly, the persistence of the contrast enhancement in MRVWI was not associated with poor outcomes. The only patient with a poor outcome had a change in FCASS from 12 to 14, while the change in FCASS did not influence the outcome in any of the other patients.

We present a series of young adults with focal cerebral arteriopathy, most of whom had an ischemic presentation (TIAs or minor strokes); a characteristic involvement of the supraclinoid ICA and proximal M1 MCA by angiography, with excellent short-term and long-term functional outcomes. Most patients had an active concentric grade 2 enhancement on MRVWI which improved in 30% of cases albeit without a correlation with functional outcomes. Although FCASS was useful in capturing the severity of the stenosis, we did not find the scores to predict outcomes as all patients had a monophasic course and 90% recovered completely from the initial event.

FCA is an uncommon cause of stroke in young adults as shown by our incidence rate of 2.8 per 1,000 person-years. This contrasts with an estimated incidence rate of 2.4% over a single year in an Irish cohort, reflecting differences in epidemiology between countries [5]. Although this previous series identified a crescendo pattern of symptom evolution, all patients in our cohort had an acute presentation and had no recurrences.

We did not find MRVWI to predict progression of stenosis, contrary to that reported in the pediatric literature [8]. However, high-resolution MRVWI helped better clarify the diagnosis in these patients as it offers additional information compared to other luminal imaging modalities. None of the patients had imaging features of alternative etiologies such as intracranial atherosclerosis, reversible cerebral vasoconstriction syndrome, or an intracranial dissection. The absence of characteristic T2/FLAIR changes and microbleeds in the MRI brain, along with the focal angiographic findings, argued against the possibility of CNS vasculitis in these patients. At the initial evaluation, it is often very difficult to differentiate between focal cerebral arteriopathy and unilateral moyamoya disease, which is another close differential. Detailed evaluation and follow-up imaging will help identify important clues such as involvement of the terminal ICA in-conjunction with the proximal M1 MCA and A1 ACA and the appearance of collateral vessels on follow-up imaging. It is important to differentiate them as the prognosis as well as management strategy varies. Recognition of FCA with confirmation by follow-up imaging often helps in prognostication as these patients often have excellent outcomes. The absence of further recurrence of ischemic events and the absence of progression of vessel stenosis may suggest FCA.

With regard to treatment, there exists no evidence-based guidelines for the management of FCA. Addition of steroids has been shown to improve functional outcomes, and antiplatelets have been shown to have reduced recurrence rates in pediatric literature [2, 9]. However, no such studies were explored in adults, and we did not find any differences between those who were treated with additional steroids compared to standard antiplatelets. In addition, based on our results, we find that persistent MR vessel wall enhancement does not necessarily mandate immunotherapy.

The strengths of our study include systematic high-resolution MRVWI at onset and follow-up. Few limitations of our case series included its retrospective nature and small size, which is expected with these rare diseases. Serum varicella IgG was not available for 60% of patients, and we were not able to verify CSF varicella IgG as it was not routinely done in our institute. Although none of our patients had a history or findings of varicella-zoster infection or reactivation, we recognize this limitation as FCA could be a para- or post-infectious phenomenon [1, 9].

FCA is an important cause of young stroke that often presents as a TIA or minor stroke, has a predilection for the supraclinoid ICA and proximal M1 MCA with very good outcomes. MR vessel wall imaging does not predict the outcomes. Future studies with larger sample sizes might shed light on the role of corticosteroids in patients with persistent vessel wall enhancement and whether they offer any additional benefit beyond antiplatelet therapy.

We are grateful to all patients who participated in this study.

The study was approved by the Institutional Ethics Committee (IEC) of Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), IEC number: 2094 on August 2023. As it was a retrospective review, a waiver of written informed consent was obtained from the IEC.

P.N. Sylaja was a member of the journal’s Editorial Board at the time of submission. All other authors declare no conflict of interest.

No funding was received for this study.

A.B. contributed to conceptualization of the study and data collection. N.K.P. analyzed the data and drafted the manuscript. A.A.K. and R.M.G. contributed to data collection and analysis. C.K., J.E.R., and S.E.S. critically revised the manuscript. S.P.N. conceptualized and designed the study, drafted the manuscript, and critically revised it.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.