A child with atypically subtle clinical presentation of acute arterial ischaemic stroke in the middle cerebral artery

Abstract

Arterial ischaemic stroke in the paediatric population is considered a rare disease, and its diagnosis is often delayed due to the subtlety and variability of clinical symptoms, especially in younger patients. The clinical presentation and imaging features of ischaemic stroke in the paediatric population are variable depending on the underlying cause, affected artery and patient’s age. Literally, acute occlusion of the middle cerebral artery shows significant clinical signs and symptoms, and riotous imaging findings due to the size of the territory. Here, we present a case of a 15-year-old boy who unusually had subtle and intermittent clinical symptoms in spite of a complete acute occlusion in his right middle cerebral artery.

Introduction

Acute ischaemic stroke (AIS) is the consequence of an abrupt cessation of adequate amounts of blood reaching parts of the brain. Paediatric AIS is a relatively rare disorder, with the estimated incidence ranging from 3−8/100,000.¹ AIS causes significant mortality and morbidity in childhood.^1,2 The most common conditions prone to paediatric AIS are cerebral arteriopathies, congenital or acquired heart diseases, and sickle cell disease. Although the clinical presentation of patients with AIS differs depending on age, the involved artery and the underlying cause, the patients usually present with a rapid-onset neurological deficit, which will depend on the extent of the infarct and hemispheric dominance, such as: focal weakness, seizure, headache, hemiparesis, localized numbness or tingling, altered mental status, vision changes or ataxia.³ The middle cerebral artery (MCA) territory is the most commonly affected territory in AIS, due to the size of the territory and the direct flow of the internal carotid artery into the MCA, providing the easiest path for thromboembolism.¹ The clinical symptoms in older children are usually persistent and obvious. However, at younger ages it can be subtle. Herein, we present a patient who had subtle and intermittent clinical symptoms and radiological findings in spite of having an acute complete occlusion in his MCA.

Case report

A 15-year-old boy was admitted to our hospital with the complaints of weakness and numbness in his left extremities lasting for 3–4 minutes, which had come 5 or 6 times a day for the previous 2 days. In his physical examination, his muscle strength was 4/5 and he had hypoesthesia in his upper left limb. The patient was hospitalized with the diagnosis of transient ischaemic attack (TIA) or cerebrovascular disease, but 1 hour later, his physical examination was normal without any motor or sensory deficit. We ordered brain magnetic resonance imaging (MRI) to exclude an ischaemic insult. We performed conventional brain MRI sequences with a 3-Tesla scanner (Verio, Siemens Medical Solutions, Erlangen, Germany). Diffusion-weighted imaging (DWI), dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion and MR angiography (MRA) with time of flight technique were also included. The apparent diffusion coefficient (ADC) map and DWI of the brain showed some foci of restricted diffusion in the right side of the periventricular–supraventricular region and the body of the right caudate nucleus related to an acute infarction (Figure 1(a) and (b)). He had no atrophy or gliosis related to chronic ischaemia on the right cerebral hemisphere consistent with previous insult. Brain MRA revealed an occlusion in the M1 segment of the right MCA (Figure 1(c)). The internal carotid arteries were equal in caliber bilaterally without any hypoplasia on the right side. The conventional MRI sequences showed T2 hyperintensities in the same region as the DWI sequences compatible with cytotoxic oedema (Figure 1(d) and (e)). Brain DSC perfusion images showed no discernible perfusion differences in either hemisphere, except the small foci in the right periventricular region. There was no diffusion–perfusion mismatch (Figure 1(f)).

Figure 1.

The apparent diffusion coefficient map (a) and the diffusion-weighted image (b) of the brain show some small foci of restricted diffusion on the right side of the periventricular–supraventricular region and the body of the right caudate nucleus related to acute infarction (white arrows). (c) Axial plane reformatted brain magnetic resonance angiography reveals the occlusion in the right middle cerebral artery (black arrow). (d) and (e) Axial plane FLAIR images show the pathological signal changes in the same region compatible with cytotoxic oedema (white arrows). (f) Brain magnetic resonance perfusion image demonstrates no significant difference in the perfusion of either hemisphere. FLAIR: fluid-attenuated inversion recovery.

Afterwards, digital subtraction angiography was performed percutaneously. The right selective carotid angiogram showed occlusion in the origin of the M1 segment of the right MCA and hypertrophic anterior cerebral artery compared to the left side (Figure 2(a)). The left selective carotid angiogram was normal (Figure 2(b)). The vertebral angiogram demonstrated the hypertrophic posterior cerebral artery in the right side compared to the left (Figure 2(c)). The distal circulation of the right MCA territory was supplied by collateral flow that was originating from the hypertrophic right anterior and right posterior cerebral arteries (Figure 2(a) and (c)).

Figure 2.

(a) The right selective carotid angiogram shows occlusion in the origin of the M1 segment of the right MCA (white arrow) and hypertrophic anterior cerebral artery (black arrow) compared to the left side. (b) The left carotid angiogram was normal with patent left MCA (white arrow) and left ACA (black arrow). (c) The vertebral angiogram was normal except the hypertrophic right PCA (white arrow) compared to the left side (black arrow). The digital subtraction angiography images show that the distal circulation of the right MCA territory was supplied by collateral flow that originated from the hypertrophic right anterior and right posterior cerebral arteries.

ACA: anterior cerebral artery; MCA: middle cerebral artery; PCA: posterior cerebral artery.

Aetiological tests including a thrombosis panel, vasculitis and viral markers (including blood varicella-zoster virus immunoglobulin (Ig)G and IgM antibody testing)), and electro- and echocardiograms were performed to be able to understand the acute occlusion. All laboratory tests were within normal limits except methylenetetrahydrofolate reductase (MTHFR) (A1298C) heterozygote mutation, low serum vitamin B12 level (96 pg/ml (187–883)) and high homocysteine level (49 mmol/l (5–15)). Urine methylmalonic acid was negative. Thus, the high homocysteine level was explained with the low serum vitamin B12 level.

The patient got heparin infusion treatment for his acute thrombotic infarction; 48 hours later, the patient’s symptoms had disappeared and his neurological examination became completely normal. Heparin therapy was arranged with low molecular weighted heparin (LMWH) and he was discharged on the 10th day after hospitalization. Six months later, his control brain MRI and DWI sequences were normal except for small foci of gliosis in the right periventricular white matter. Right MCA was not observed on MRA. The homocysteine level had fallen to 8 mmol/l after treatment with vitamin B12 for 6 months. After using LMWH for 6 months, his treatment was changed from LMWH to acetylsalicylic acid. He is still undergoing acetylsalicylic acid treatment.

Discussion

The MCA territory is the most commonly affected area in a cerebral infarction due to the large size of the territory and the direct flow from the internal carotid artery into the MCA, providing the easiest path for thromboembolism.^1,3 In an adult brain, acute proximal MCA occlusion (M1–M2 segment) generally causes contralateral hemiparesis, contralateral hemisensory loss, hemianopsia, aphasia (if the dominant hemisphere is involved) or neglect (if the non-dominant hemisphere is involved). Although the present case had an occlusion of the M1 segment of the right MCA on angiography, the silent clinical findings make this case interesting. The absence of right hemispheric atrophy or a gliotic signal on the patients’ first brain MRI was very helpful for us to exclude chronic MCA occlusion. Moreover, the symmetric caliber of the bilateral internal carotid artery (ICA) was an important finding for the exclusion of right MCA hypoplasia or aplasia. Moreover, the patients’ MCA occlusion was not a transient occlusion, because the MCA flow did not return on follow-up MRAs. Although the patient had acute right MCA occlusion, the right anterior and posterior cerebral arteries that were hypertrophic and increased in calibre compared to the left side, compensating for the right MCA territory as much as possible. Generally, the development of collateral circulation takes some time, but in our patient who was having an acute MCA infarction, the collateral circulation could compensate for the MCA territory more rapidly and protect the patients’ motor and sensory functions substantially. This may be related to the plasticity of the brain in childhood. Our second hypothesis is that there may be a congenital vascular variation in which the right MCA may be hypoplastic congenitally, and the right anterior cerebral artery (ACA) and the posterior cerebral artery (PCA) may be hyperplastic. That is why the hyperplastic PCA and the ACA could compensate the MCA territory, but when a stressful situation arose, stroke in the MCA territory could not be prevented. This vascular variation hypothesis (the hypertrophic PCA and the ACA, and the hypoplastic MCA) could also explain the symmetric caliber of the bilateral ICAs. Moreover, we thought that MTHFR heterozygous mutation, a low serum vitamin B12 level and a high homocysteine level might be important factors to the occurrence of stroke aetiologically.

Transient short-term extremity numbness is frequently seen in the adolescent population and may be a precursor of an arterial circulation disturbance. The World Health Organization describes stroke as a clinical syndrome of a rapidly developing focal or global disturbance of brain function, lasting >24 hours or leading to death with no obvious non-vascular cause.⁴ On the other hand, TIA is defined as a sudden, focal neurological deficit that lasts for <24 hours, confined to an area of the brain or eye perfused by a specific artery.⁵ Our patient, who had silent clinical findings, was hospitalized with an initial diagnosis of TIA that turned out to be AIS.

Unlike in adults, AIS is rarely seen in the paediatric population.⁶ Moreover, the aetiological factors and the clinical symptoms of AIS in paediatric patients are also quite different from adults.^4,7,8 In adults, the underlying causes of stroke are related to atherosclerosis, hypertension, hypercholesterolaemia, smoking and diabetes mellitus. In paediatric patients, the leading causes of stroke are coagulation disorders, cardiac diseases, cerebral vasculopathy or an inborn error of metabolism (hyperhomocystinaemia, Fabry disease etc).^2–4,8–10 Our patient had a heterozygous MTHFR mutation and high homocysteine levels, with low serum vitamin B12 levels. The clinical presentation of ischaemic stroke in the paediatric population varies according to a patient’s age. In early childhood, the symptoms are non-specific, thus the diagnosis of stroke is frequently delayed,⁷ but in adolescent age group, the patients may present with severe acute neurological symptoms (hemiparesis, speech and vision disturbance, cranial nerve deficits etc.).^9,11 However, if the infarct size is small in the early period, symptoms may be subtle.^3,12,13

The imaging features of ischaemic stroke in children are variable depending on the underlying cause and affected artery. The localization and the size of the infarction are important. Generally, an arterial territory or the border zones between the major vascular territories are affected depending on the cause of the ischaemia. Acute ischaemic stroke typically involves the major arterial territory. It is easily identified early on by MRI as regions of bright signal on DWI and decreased signal on ADC maps within a vascular territory. The reduction in ADC values due the presence of acute ischaemic necrosis and cellular swelling lasts up to 2 weeks. The loss of grey–white matter differentiation, which is an indirect finding of cytotoxic oedema, can be seen on T2-weighted images and FLAIR sequences, but it may be negative during the first few hours. MRA is very helpful for the detection of complete occlusion in a major artery. Catheter angiography remains the gold standard for imaging diagnosis in arterial ischaemic stroke as is exhibits the stenosis or occlusion clearly, and the accompanying small collateral vessels can be seen easily.^{6,9,10,12–16}

Conclusion

To conclude, here we presented a patient who had subtle and intermittent clinical symptoms in spite of having an acute complete occlusion in his MCA. When a patient comes with a suspicion of stroke, neuroimaging has a crucial role in the diagnosis and selection of the appropriate and immediate treatment modality. That is why it should be performed immediately. With the increasing awareness of the subtle clinical symptoms in paediatric stroke patients, this knowledge may help to provide a straightforward diagnosis and to quickly achieve appropriate treatment with the support of imaging techniques.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.