Neuroradiology/Head and Neck Imaging
Original Research
Prevalence of White Matter Hyperintensity in Young Clinical Patients
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OBJECTIVE. The purpose of this study was to investigate the prevalence of white matter hyperintensity (WMH) without specific causes in young clinical outpatients.
MATERIALS AND METHODS. A total of 1249 young clinical outpatients who underwent an unenhanced head MRI examination between January 1, 2016, and December 31, 2016, were included in the study. The chi-square test was used to analyze differences in the prevalence and characteristics of WMH by sex, age, and history of cardiovascular disease (CVD). The prevalence of WMH among clinical patients with neurologic symptoms was also compared with that among participants without neurologic symptoms. Logistic regression was used to identify the patient characteristics that were the best predictors of WMH.
RESULTS. The overall prevalence of WMH was 25.94% (324/1249). Most patients with WMH (85.49% [277/324]) had mild WMH, mainly in frontal and parietal subcortical white matter. There was no significant difference in the prevalence of WMH by sex (p > 0.05), but the prevalence of WMH was higher among older patients (p < 0.001) and patients with a history of CVD (p < 0.001). Compared with participants without neurologic symptoms, clinical patients with dizziness (p = 0.029) and light-headedness (p = 0.001) were more likely to have WMH, which was attributed to older age and CVD. Logistic regression analysis showed that age and CVD were the best predictors of WMH.
CONCLUSION. WMH is frequently found in young clinical patients. Most WMH is the mild type and mainly located in frontal and parietal subcortical white matter. Older age and CVD are risk factors for WMH.
Keywords: MRI, prevalence, white matter hyperintensity, young patients
With the wide use of brain MRI, white matter hyperintensity (WMH) is frequently observed in clinical patients. Although some WMH is associated with specific causes, such as lacunar infarction, traumatic brain injury, and demyelinating disease [1–3], some WMH has no specific cause, especially in young patients. Incidental WMH without a detected cause can be extremely distressing for these patients [4, 5]. Thus, it is of utmost importance to determine the natural course of WMH with an undetected cause and its relation to neurologic symptoms. To solve this problem, the prevalence and distribution of WMH with undetected causes should be investigated first.
A number of studies [6–8] have evaluated the presence of incidental WMH in healthy populations. Other studies have shown that the prevalence of WMH in healthy populations ranges from 5.3% to 100%, depending on the inclusion criteria [9–12]. Most studies have shown that WMH lesions tend to be small, but they grow with age, especially among people older than 55 years. However, previous studies have mainly focused on middle-aged or older healthy populations. Studies of the prevalence and distribution of WMH in young clinical populations (≤ 45 years old) are rare.
We have observed WMH without a specific cause in young clinical populations in our practice from time to time. Because WMH is observed mostly in older populations, detection of WMH has been very disconcerting to these younger patients. The aim of this retrospective study was to investigate the prevalence and characteristics of WMH with undetected causes in a young clinical population to deepen our understanding of WMH in this population.
| Materials and Methods |   |
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This study was approved by the local institutional review board with a waiver of the requirement for informed consent because of the retrospective nature of the study. A total of 1249 outpatients (575 male patients, 674 female patients; age range, 1–45 years) who underwent an unenhanced head MRI examination between January 1, 2016, and December 31, 2016, were included in this study. Patients with specific causes of WMH were excluded. If multiple brain MRI examinations had been performed, only the first brain MRI examination was used for this study. The exclusion criteria were as follows: history of stroke, traumatic brain injury, neoplasm, psychiatric illness, demyelinating disease, metabolic disease, or substance abuse.
Most of the participants (94.32% [1178/1249]) had neurologic symptoms (including 72 patients with unspecified symptoms, whose MRI application forms stated “suspicious of cerebrovascular disease”). The 71 participants (5.68%) with no neurologic symptoms underwent head MRI examinations as part of a physical examination.
MRI was performed by trained technicians with 3-T systems (Magnetom Verio, Siemens Healthcare; Achieva, Philips Healthcare; Ingenia, Philips Healthcare). The brain MRI protocol at our institution included axial T1-weighted, axial T2-weighted, axial FLAIR, axial DWI, and sagittal T1-weighted sequences.
Demographic and clinical information (age, sex, main clinical symptoms for performing brain MRI) of each participant was collected, including information about cardiovascular disease (CVD), that is, hypertension, diabetes, and hyperlipemia. Two trained neuroradiologists evaluated the head MR images of each participant, and any disagreements were resolved by consensus.
WMH was characterized by isointensity on T1-weighted images and high signal intensity on T2-weighted and FLAIR images. On the basis of previous research findings, WMH was separated into two broad categories: deep and periventricular, depending on the proximity of the WMHs to the lateral ventricles [13]. Deep WMH was further classified as frontal, parietal, insular, temporal, occipital, or cerebellar WMH [13, 14]. The severity of WMH was classified as follows: mild, that is, punctate or discrete foci ≤ 3 mm in diameter for deep WMH or frontal or occipital caps of the lateral ventricles for periventricular WMH; moderate, that is, punctuate or discrete foci > 3 mm in diameter for deep WMH or a smooth halo along the whole periventricular area for periventricular WMH; and severe, that is, confluent foci or a confluence widely distributed throughout the white matter for deep WMH or irregular periventricular WMH extending partially into the deep white matter or extending throughout the deep and subcortical white matter for periventricular WMH [13, 15] (Fig. 1).
 View larger version (130K) | Fig. 1A —Levels of severity of white matter hyperintensity (WMH). A, 24-year-old man with headache. Axial FLAIR MR images show mild WMH in right frontal and parietal lobes. |
 View larger version (141K) | Fig. 1B —Levels of severity of white matter hyperintensity (WMH). B, 35-year-old woman with dizziness. Axial FLAIR MR images show moderate bilateral WMH in frontal and parietal lobes. |
 View larger version (134K) | Fig. 1C —Levels of severity of white matter hyperintensity (WMH). C, 28-year-old man with hearing disturbance. Axial FLAIR MR images show severe bilateral WMH in frontal and parietal lobes and periventricular area. |
Statistical tests were performed with SPSS for Microsoft Windows software (version 20.0, IBM). Categoric variables were summarized as numbers and percentages. The chi-square test was used to analyze the demographic and clinical characteristics of the study participants with and without WMH. The difference in distribution of WMH between participants with neurologic symptoms and participants without neurologic symptoms was also analyzed by chi-square test. Logistic regression was performed by means of the backward stepwise procedure based on a likelihood ratio test with p > 0.10 for exclusion from the model. The criterion for statistical significance was p < 0.05.
| Results | |
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Of the 1249 study participants, 324 (25.94%) had WMH. There was no statistically significant difference in sex between the WMH group (75.48% [434/575] female patients, 24.52% [141/575] male patients) and the group without WMH (72.85% [491/674] female patients, 27.15% [183/674] male patients) (p = 0.291). WMH was more frequently detected in the 31- to 45-year-old age group (32.55% [276/848]) than the 16- to 30-year-old age group (12.54% [44/351]) and the 1-to 15-year-old (8.00% [4/50]) group (p < 0.001). The prevalence of WMH was also higher among patients with a history of CVD (46.84% [37/79]) than patients without a history of CVD (24.53% [287/1170]) (p < 0.001).
Most of the participants in the WMH group had the mild type of WMH (85.49% [277/324]), followed by the moderate type (12.96% (42/324]) and severe type (1.54% (5/324]). As for the distribution of WMH by brain region, 97.84% (317/324) of patients had deep WMH and 33.64% (109/324) of patients had periventricular WMH. Among patients with deep WMH, WMH was mostly located in the frontal lobe (91.98% [298/324]) and parietal lobe (58.95% [191/324]), followed by the insular lobe (10.80% [35/324]), temporal lobe (5.56% [18/324]), occipital lobe (2.78% [9/324]), and cerebellum (1.54% [5/324]). When focusing on participants in the WMH group without neurologic symptoms, we found that all 11 participants with WMH had deep WMH, located in the frontal lobe (90.91% [10/11]) and parietal lobe (45.45% [5/11]). We also found that 45.45% (5/11) of participants without neurologic symptoms had periventricular WMH.
Compared with participants without neurologic symptoms (15.49%), more clinical patients with dizziness (28.33%; p = 0.029), light-headedness (43.59%; p = 0.001), and unspecified symptoms (44.44%; p = 0.001) had WMH (Table 1). Table 2 shows that patients with dizziness, light-headedness, and unspecified symptoms were older and more likely to have a CVD history than participants without neurologic symptoms. Logistic regression showed that age (31–45 years; odds ratio, 5.173; p = 0.002) and a history of CVD (odds ratio, 2.090; p = 0.002) were the best predictors of having WMH.
| Discussion | |
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We investigated the prevalence and characteristics of WMH with undetected causes in a young clinical population and found the prevalence of WMH was 25.94% in this population. Most of the patients with WMH had the mild type, which was mainly located in frontal and parietal subcortical white matter. Older age and a history of CVD were risk factors for WMH.
WMH has mainly been observed in older populations. Wen et al. reported that the prevalence of WMH was 100% in healthy people 60–64 years old [10] and 50.9% in healthy people 44–48 years old [11]. Hopkins et al. [9] found that the prevalence of WMH was 5.3% across a broad age range (16–65 years) and that older people were more likely to have WMH. The prevalence of WMH in our study was 25.94%. This was expected because the participants in our study were fairly young, but most of them had symptoms.
Our study also showed that older patients and patients with a history of CVD were more likely to have WMH. Logistic regression analysis confirmed that older age and CVD history were risk factors for WMH. A possible cause of the increase in WMH with age could be that the function of the cerebral vessels decreases with age. CVD may contribute to WMH because it can lead to cerebral atherosclerosis and hemodynamic changes, causing brain ischemia and demyelinating disorders [16]. Previous studies have shown that hypertension [17] and diabetes [18] are associated with WMH in older people. Our results showed that even among young clinical patients, older age and a history of CVD were important risk factors for WMH. Therefore, in clinical practice, when WMH is incidentally found, the radiologists and ordering clinicians should pay attention to the patient's age and CVD history, inquiring in detail about the CVD history.
The most common sites of WMH in this study were the frontal lobe, parietal lobe, and periventricular area. That the deep white matter is more prone to the effects of arteriosclerosis and that the lenticulostriate branches of the anterior and middle cerebral arteries are the most affected vascular regions may explain why deep WMH was mainly observed in the frontal and parietal lobes [19]. Periventricular white matter is also prone to damage, because it is supplied by ventriculofugal vessels arising from subependymal arteries, which tend to be more strongly influenced by hemodynamic factors [19].
To our knowledge, no previous studies have compared the prevalence of WMH in patients who have neurologic symptoms and those who do not. Our study showed that patients with dizziness, light-headedness, and unspecified symptoms were more likely to have WMH than those who did not have neurologic symptoms. However, patients with dizziness, light-headedness, and unspecified symptoms in our study were older and more likely to have CVD, and logistic regression analysis did not identify these patients' symptoms as risk factors for WMH. The significant differences in symptom distribution of WMH might have resulted from differences in the ages and CVD histories of the groups.
The results of this study should be interpreted in the context of the following limitations. First, the study did not include information about environmental factors, such as daily food intake, sleep duration, and exercise. Results of previous studies [19, 20] suggest that genetic factors alone or in combination with environmental factors may play a role in the formation of WMH. Yaffe et al. [21] reported that short sleep duration was associated with markers of poor white matter integrity in midlife. Further research is warranted to investigate the underlying causes of WMH in young clinical patients. Second, the study sample may reflect selection bias. The prevalence of WMH in clinical patients may be different at other institutions because it can vary with different brain MRI examination criteria and other factors. Nevertheless, our study did reveal the overall prevalence of WMH in young patients. Third, although we found association between age, CVD, and WMH, we could not confirm the order of causal effect. Future prospective studies are needed to confirm our conclusion and further work out a possible guidance plan for the young clinical population with WMH. Fourth, the sample size in this study was fairly small. Prospective studies with larger samples are needed to confirm our findings.
Supported by national Natural Science Foundation of China (81871329, 81471656, 81671673), Outstanding Subject Leader of Shanghai Municipal Health Planning Commission (2017BR041), Shanghai Municipal Science and Technology Commission Medical Guide Project (16411968900), and Shanghai Key Discipline of Medical Imaging (2017ZZ02005).
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