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The different infarct patterns between adulthood-onset and childhood-onset moyamoya disease
  1. H J Cho1,
  2. Y H Jung1,
  3. Y D Kim1,
  4. H S Nam1,
  5. D S Kim2,
  6. J H Heo1
  1. 1Department of Neurology, Yonsei University College of Medicine, Seoul, Korea
  2. 2Department of Neurosurgery, Yonsei University College of Medicine, Seoul, Korea
  1. Correspondence to Ji Hoe Heo, Department of Neurology, Yonsei University College of Medicine, 250 Seongsan-no, Seodaemoon-gu, 120-752, Seoul, Korea; jhheo{at}yuhs.ac

Abstract

Background and purpose The pattern of infarctions based on the findings of diffusion-weighted image was assessed, and it was also investigated whether there are any age-specific differences in patients with moyamoya disease (MMD).

Methods The subjects were 66 consecutive patients with MMD who had an acute cerebral infarction. Each ischaemic lesion was categorised into one of seven patterns (gyral, atypical territorial, honeycomb, classic territorial, multiple-dot, borderzone, deep lacunar) based on diffusion-weighted image findings. The patterns were compared between adulthood-onset MMD (A-MMD, ≥20 years old, 34 patients) and childhood/adolescent-onset MMD (C-MMD, <20 years old, 32 patients) according to their ages of infarct presentation.

Results A total of 91 infarct patterns were observed from 66 patients. The gyral, atypical territorial, and honeycomb patterns, which are not usually seen in conventional stroke patients, were common in MMD (68.1%). Among all patterns, a gyral pattern was most common (40/91, 44.0%). Borderzone and deep lacunar patterns were infrequent. Gyral and borderzone patterns were more frequently seen in the C-MMD group, whereas a honeycomb pattern was not seen in young patients. Honeycomb pattern was more common at advanced vascular stages. Infarctions confined to the cortex were more common in the C-MMD group (26/32, 75.0%) than in A-MMD patients (14/34, 41.2%).

Conclusions Moyamoya disease showed various characteristic and age-specific infarct patterns. Different infarct patterns between the A-MMD and C-MMD groups may be associated with age-specific vulnerability of the brain to ischaemia, stage of arteriopathy or changes of abnormal collateral pathways.

  • Cerebral arteries
  • moyamoya disease
  • infarction
  • diffusion-weighted imaging
  • angiography
  • cerebrovascular disease
  • MRI
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Moyamoya disease (MMD), which is a progressive arteriopathy of unknown origin, is an uncommon cause of cerebral infarctions.1 Infarct patterns are greatly influenced by mechanisms leading to arterial occlusion, the presence of collateral pathways and vulnerability of the brain to ischaemia. Infarctions in MMD may be peculiar because they frequently develop during infancy and childhood and are accompanied by abnormal vascular networks and prominent collateral vessels. Therefore, patients with MMD may have distinct infarct patterns from those with conventional stroke that usually occur in adults. However, few studies have investigated infarct patterns in patients with MMD.2–4

Moreover, infarct patterns may be different between patients with adulthood-onset MMD (A-MMD) and childhood/adolescent-onset MMD (C-MMD) because arteriopathy and the degree of collateral vessels change as the disease progresses. In this study, we assessed the patterns of infarctions based on findings of diffusion-weighted image (DWI) and their differences between A-MMD and C-MMD patient populations.

Materials and methods

Patients

The subjects were 66 consecutive patients with MMD who had an acute cerebral infarction demonstrated on DWI and who had been admitted to a single university hospital during the period from March 1999 to December 2007. The diagnosis of MMD was based on previously admitted criteria.1 4 All patients underwent MRI with DWI, an angiographic study (conventional angiography in 54 patients or MR angiography (MRA) in 12 patients) and standard laboratory tests to exclude other causes. The angiographic stages of MMD were evaluated based on the criteria by Suzuki and Takaku (web-only table 1).5 6 This study was approved by the Institutional Review Board of Severance Hospital, Yonsei University Health System.

Analysis of imaging data

For this study, the first ischaemic events from 66 patients were analysed. Ischaemic lesions on DWI were classified into seven patterns based on their shape, distribution and location, which included gyral, atypical territorial, honeycomb, classic territorial, multiple-dot, borderzone and deep lacunar patterns (figure 1, web-only table 2).

Figure 1

Representative diffusion-weighted images of each infarct pattern. (A) Gyral pattern; (B) atypical territorial; (C) honeycomb; (D) classic territorial; (E) multiple-dot; (F) borderzone; (G) deep lacunar.

Each ischaemic lesion could be categorised as one of the seven patterns. The patterns were further grouped into the unusual types (gyral, atypical territorial and honeycomb patterns) and the usual types that can be typically seen in conventional stroke patients (territorial, multiple-dot, borderzone and deep lacunar pattern). The ischaemic event was dichotomised into A-MMD (≥20 years old) and C-MMD (<20 years old) according to the age of presentation with an acute infarction. The patterns of infarctions and angiographic stages were compared between the two groups.

Statistical analysis

Fisher exact tests and Pearson χ2 tests were used for comparisons of the baseline characteristics, infarct patterns and locations of infarctions. Univariate ANOVA test was used for analysis of relationship between age or stroke patterns and angiographic stages. p<0.05 was considered statistically significant. The statistical analyses were performed with SPSS for Windows (SPSS V.13.0, SPSS Inc.).

Results

Demographic characteristics

Included in the A-MMD group were 34 patients (17 men, median age 40.4 years), whereas 32 patients (12 boys, median age 6.5 years) constituted the C-MMD group. Conventional risk factors for stroke were found in 12 patients, which included hypertension in ten patients, diabetes mellitus in three, smoking in four and atrial fibrillation in two. However, they showed characteristic angiographic findings of MMD, and none of them demonstrated evidence of atherosclerosis in other extracranial, intracranial and systemic vessels.

Infarct patterns

A total of 91 patterns were detected from infarction of 66 patients. Infarction of 43 patients showed one pattern, 21 demonstrated two patterns, and 2 showed three patterns. The most common pattern was a gyral pattern, followed by an atypical territorial pattern (table 1). The unusual type constituted 68.1% of the total patterns. These unusual types were more common in the C-MMD group (32/40, 80.0%) than in the A-MMD group (30/51, 58.8%, p=0.001). These patterns were not different between patients with conventional risk factors for stroke and those without them within the A-MMD (the unusual type made up 42.9% of patients with risk factors vs 57.1% in those without risk factors, p=0.212). A honeycomb pattern was more common at advanced vascular stages (web-only table 3).

Table 1

Frequency of each infarct pattern in adulthood and childhood/adolescent-onset patients

The frequency of each pattern was different between the groups (p=0.001, table 1). In the A-MMD group, all patterns were found in a relatively even manner between 3.9% and 27.5%. However, in the C-MMD group, the gyral pattern was most commonly seen, whereas the honeycomb pattern was not observed (table 1). Gyral and borderzone patterns were seen in patients at younger ages, whereas honeycomb and classic territorial patterns were seen after later teenage (web-only figure 1).

Location of infarctions

The lesions were confined to the cortex more frequently in the C-MMD group (24/32, 75.0%) in than the A-MMD group (14/34, 42.1%,), whereas cortical plus subcortical infarctions were more frequent in the A-MMD group (13/34, 38.2%) than in the C-MMD group (4/32, 12.5%, p=0.017, web-only figure 2). The most frequently involved lesion was in the frontal lobe in both groups (A-MMD group 64.7%, C-MMD group 87.5%).

Angiographic stage

Advanced vascular stages were associated with increase of age (p=0.042, web-only figure 3a). Stage 3 was most common in the C-MMD group, whereas stage 4 was most common in the A-MMD group. A-MMD group showed more advanced vascular stages (p=0.034, web-only figure 3b).

Discussion

This study demonstrated that patients with MMD showed various and characteristic infarct patterns, some of which are not usually seen in conventional stroke patients. In addition, the frequency and distribution of each pattern was different according to the age of onset of the infarctions in this study.

Patients with MMD showed some characteristic infarct patterns that are not usually seen in conventional stroke patients, which included gyral, atypical territorial and honeycomb patterns. These peculiar features may be associated with age-related selective vulnerability of the cortical gray matter to the ischaemia, development/regression of pial collaterals and distorted classic vascular territory.7

In our study, certain infarct patterns demonstrated age-specific preponderance. Gyral and borderzone patterns tended to develop during younger ages, whereas a honeycomb pattern was not observed in the C-MMD group. This may in part be associated with the selective vulnerability of the cortical gray matter in infant patients. Cortical neurons use more oxygen-glucose than white matter.7 Ischaemic insults to the brain of infants and children are known to damage the cerebral cortex and deep nuclei preferentially8 9 because these brain areas express specific amino acid receptors that entail high metabolic demands during infancy.10 In C-MMD patients, blood flow is markedly reduced in the cortex. As a result, minor ischaemic insults could produce severe damage in these cortical areas selectively, particularly in the C-MMD group.

As ages of infarction presentation increased, the honeycomb pattern became more predominant in the cortex. Leptomeningeal collaterals from the posterior cerebral artery (PCA), which were scant during the early stages of MMD, develop prominently as the stage progresses.3 However, as the stages of MMD advance further, these collaterals decrease significantly.11 The honeycomb pattern of infarctions is known to appear in these advanced PCA stages,3 which was also demonstrated in this study. Although the exact mechanism is unknown, it might be due to irregular defects in the blood supply provided by leptomeningeal collaterals from the PCA.3

Our data showed that the borderzone infarction pattern had a low prevalence. Usually, there are no connections between the lenticulostriate arteries and the terminal medullary arteries of the middle cerebral artery, and the area between them constitutes the borderzone. However, in MMD, an anastomosis may be formed between the basal moyamoya vessel and the terminal medullary branches, which prevent the occurrence of this pattern of infarctions.12 In addition, the location of a classic borderzone area could change as the disease progresses because progressive narrowing of the arteries may alter their vicinity of arterial supply.

An analysis of infarct patterns may provide some clues to the etiologic mechanism of infarctions. Extreme hypoperfusion by progressive occlusion of the cerebral artery has been regarded as a generally plausible mechanism of infarctions in MMD. However, thrombus-related occlusion may also play a role. It has been suggested that large infarctions in MMD result from thromboembolism.13 In high-grade atherosclerotic ICA disease, a pattern of multiple small cortical infarctions on DWI like those seen in our patients is frequent, and thromboembolism is suggested as the probable mechanism.14 Histopathologic studies in autopsied patients with MMD frequently showed thrombus formation in the diseased arteries.15 All these findings along with our observations support a contributing role of thrombotic or thromboembolic mechanism in developing infarctions in patients with MMD.

In conclusion, the present study, which was based on DWI, showed the presence of characteristic infarct patterns in patients with MMD. In addition, the infarct patterns suggest that thrombotic mechanisms, as well as haemodynamic mechanisms, are responsible for infarctions in MMD. The age-specific appearance of some infarct patterns may reflect the dynamic features of arteriopathy, as well as the growth/regression of collateral pathways occurring throughout the life span.

Acknowledgments

The authors thank Dr Chung Mo Nam for his assistance of statistical analysis.

References

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Supplementary materials

Footnotes

  • Funding This work was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea (A080602, A085136).Other funders: Ministry for Health, Welfare & Family Affairs, Republic of Korea.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the institutional review board of the Severance Hospital, Yonsei University Health System.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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