Clinical characteristics of children with cerebral white matter abnormalities.

The rapidly expanding use of magnetic resonance imaging (MRI) in children with neurological impairments of unknown aetiology has revealed a large number of children with abnormalities of the cerebral white matter, some with leukodystrophy-like white matter abnormalities on MRI, but non-progressive in clinical presentation and course. The aim of this study was to investigate the clinical and neuroradiological characteristics of 26 children with white matter abnormalities of unknown origin and to find diagnostic clues or indicators of progressive versus nonprogressive disease. The typical child with white matter abnormalities was characterized by onset of symptoms within the first year of life, most often presenting as general developmental delay and hypotonia. Later-appearing signs were spasticity and ataxia and as a rule severe learning and motor disabilities. Serious ophthalmological signs were frequently seen. Perinatal adverse events were rare, infectious aetiologies not indicated but prenatal stigmata relatively common. The clinical course was progressive in 11 children and non-progressive in 15. Late onset presentation was associated with a progressive course whereas prenatal stigmata and asymmetrical white matter lesions only were found in children with a non-progressive disorder. The MRI showed three main patterns: a) a generalized increase of the T2 signal of the white matter in 12 children, b) a bilateral, symmetric but not generalized abnormality in nine and c) asymmetric, focal or multifocal pathology in five. Useful information as to clinical entities and course was obtained from the combined clinical and radiological assessment. A precise nosological diagnosis could be made in six cases. The study showed that white matter abnormalities in children constitute a heterogeneous group of rare and 'anonymous' conditions, motivating collaborative studies for further clarification of background and management.     

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??Abstract??Objective The purpose of this study was to use diffusion tensor imaging to investigate the status of cerebral white matter??WM?? maturation in the first 2 years after birth. Methods A total of 67 children ranging in age from birth to 24 months underwent conventional MRI and diffusion tensor imaging with gradient encoding in fifteen directions?? all on a 1.5T MRI system. All children were divided into six groups according to month. Fractional anisotropy was measured in five deep WM structures ??posterior limb of internal capsule?? anterior limb of internal capsule?? genu and splenium of corpus callosum?? optic radiation?? and four peripheral WM regions??associational WM underlying prefrontal?? occipital cortex?? temporal lobe and centrum semiovale??. Results In the same months of age?? different parts of the white matter FA values were significantly different??the deep white matter FA values were higher than the shallow??in birth-to-28 days baby?? corpus callosum FA values was the highest in deep white matter ??followed by the corpus callosumknee?? posterior limb of internal capsule?? optic radiation and limb of internal capsule??in the shallow white matter??centrum semiovale was the highest?? followed by the temporal lobe?? frontal lobe and occipital subcortical white matter. With increasing month-old?? white matter FA values of the various parts gradually increased??showing positive correlation. In the same parts of the white matter??FA values change in different rate for different ages??which was a statistically significant ??P??0.05??. Conclusion Combination of T1WI and T2WI and diffusion tensor imaging can be used for quantitative evaluation of cerebral white matter development of children in the first 2 years after birth..     

四氢生物喋呤缺乏症治疗前后神经系统表现及其脑白质病变分析

目的 对比治疗前后四氢生物喋呤缺乏症(tetrahydrobiopterin deficiency,BH4D)的神经系统表现,并观察其治疗前后脑白质的病变,为判断治疗效果提供客观的临床和影象学依据。方法 BH4D患儿11例,男9例,女2例;年龄17周～4岁。给予四氢生物喋呤,美多巴,5-羟色胺口服治疗1年,行头颅MRI检查,采用staudt评估标准,对其脑白质病变进行治疗前后的观察评定,其中8例以Gesell发育量表测量进行量化比较。结果 ①治疗后8例Gesell发育量表发育指数较治疗前改善。②治疗前1l例患儿(100％)均有髓鞘发育延迟,其中额叶11例(100％,),枕叶8例(72．7％),颞叶4例(36．4％),顶叶3例(27．3％),胼胝体发育不良6例(54．5％),1例小脑发育不良,全部病例在双侧侧脑室周围T2加权像(T2WI)上均有弥漫性高信号病灶。治疗后脑白质病变较前好转,但仍存在部分髓鞘发育延迟及T2WI异常高信号。结论 治疗后BH4D患儿发育指数较前好转,临床症状的改善与脑白质病变具有一致性;BH4D患儿脑白质病变具有高发生率,表现为髓鞘发育延迟及异常的T2WI高信号,推测这种损害不仅与高苯丙氨酸血症有关,且与神经递质的合成下降有关;治疗后的脑白质病变较治疗前改善,与临床症状的改善相一致,但依然存在部分脑白质病变,推测与治疗所用的BH4的剂量,及个体差异所造成的血药浓度及透过血脑屏障的浓度不同有关。     

Quantitative analysis of the corpus callosum in children with cerebral palsy and developmental delay: correlation with cerebral white matter volume

Background: The direct quantitative correlation between thickness of the corpus callosum and volume of cerebral white matter in children with cerebral palsy and developmental delay has not been demonstrated. Objective: This study was conducted to quantitatively correlate the thickness of the corpus callosum with the volume of cerebral white matter in children with cerebral palsy and developmental delay. Material and methods: A clinical database of 70 children with cerebral palsy and developmental delay was established with children between the ages of 1 and 5 years. These children also demonstrated abnormal periventricular T2 hyperintensities associated with and without ventriculomegaly. Mid-sagittal T1-weighted images were used to measure the thickness (genu, mid-body, and splenium) and length of the corpus callosum. Volumes of interest were digitized based on gray-scale densities to define the hemispheric cerebral white matter on axial T2-weighted and FLAIR images. The thickness of the mid-body of the corpus callosum was correlated with cerebral white matter volume. Subgroup analysis was also performed to examine the relationship of this correlation with both gestational age and neuromotor outcome. Statistical analysis was performed using analysis of variance and Pearson correlation coefficients. Results: There was a positive correlation between the thickness of the mid-body of the corpus callosum and the volume of cerebral white matter across all children studied (R=0.665, P=0.0001). This correlation was not dependent on gestational age. The thickness of the mid-body of the corpus callosum was decreased in the spastic diplegia group compared to the two other groups (hypotonia and developmental delay only; P<0.0001). Within each neuromotor subgroup, there was a positive correlation between thickness of the mid-body of the corpus callosum and volume of the cerebral white matter. Conclusion: The thickness of the mid-body of the corpus callosum positively correlates with volume of cerebral white matter in children with cerebral palsy and developmental delay, regardless of gestational age or neuromotor outcome. Assessment of the thickness of the corpus callosum might help in estimating the extent of the loss of volume of cerebral white matter in children with a broad spectrum of periventricular white matter injury.     

Extensive white matter abnormalities associated with neonatal Parechovirus (HPeV) infection

White matter changes in the neonatal period are commonly associated with hypoxic-ischaemic injuries and, less frequently, infections. Enteroviral (EV) meningoencephalitis as a cause of extensive white matter changes in newborns is well documented but Human Parechovirus (HPeV) associated with a similar picture has only been recently recognized. We report a case of HPeV-related neonatal meningoencephalitis associated with extensive white matter abnormalities, giving rise to a wide differential diagnosis including consequences of hypoxic-ischaemic encephalopathy (HIE) and periventricular leucomalacia (PVL). This case highlights the importance of excluding both EV and HPeV infection in neonates presenting with signs and symptoms of encephalitis. Moreover, HPeV infection ought to be considered in infants with white matter changes suggestive of HIE but no convincing history of a perinatal hypoxic-ischaemic insult.     

Patchy cerebral white matter edema in chronic renal failure

Bilateral patchy cerebral white matter edema was observed in two children with chronic renal failure. Uremia in one case and hypertension or hyponatremia in the other appeared to be the cause of the neurological and radiological findings.     

新生儿脑白质损伤的定量评价

目的 利用超声灰度值测定评价定量分析技术对新生儿脑白质损伤诊断的意义.方法 通过颅脑超声及应用医学图像分析软件,对121例不同胎龄新生儿脑白质进行灰度值测定,并以白质回声是否在1个月内恢复正常将白质损伤分为轻度和重度,研究不同程度白质损伤的灰度值特点,并比较早期灰度值与后期神经发育的关系.结果 新生儿脑白质轻度损伤、重度损伤、对照组之间,早期白质灰度值差异有统计学意义(P＜0.01);随灰度值的增加,白质重度损伤的比率增加(P＜0.05);早期白质灰度值＞130者3～6个月时出现神经发育异常(主要是肌张力和适应性异常)的比率显著增加(P＜0.05).结论 超声灰度定量分析对新生儿脑白质损伤的诊断有重要意义,有助于判断预后和指导临床早期治疗.     

Pathogenesis of cerebral white matter injury of prematurity

Cerebral white matter injury, characterised by loss of premyelinating oligodendrocytes (pre-OLs), is the most common form of injury to the preterm brain and is associated with a high risk of neurodevelopmental impairment. The unique cerebrovascular anatomy and physiology of the premature baby underlies the exquisite sensitivity of white matter to the abnormal milieu of preterm extrauterine life, in particular ischaemia and inflammation. These two upstream mechanisms can coexist and amplify their effects, leading to activation of two principal downstream mechanisms: excitotoxicity and free radical attack. Upstream mechanisms trigger generation of reactive oxygen and nitrogen species. The pre-OL is intrinsically vulnerable to free radical attack due to immaturity of antioxidant enzyme systems and iron accumulation. Ischaemia and inflammation trigger glutamate receptor-mediated injury leading to maturation-dependent cell death and loss of cellular processes. This review looks at recent evidence for pathogenetic mechanisms in white matter injury with emphasis on targets for prevention and treatment of injury.     

Hypothyroxinemia of prematurity and the risk of cerebral white matter damage.

OBJECTIVE: Infants with hypothyroxinemia of prematurity (HOP) are at increased risk for neurodevelopmental dysfunction. Infants born near the end of the middle trimester are also at increased risk for an echolucency (EL) in the cerebral white matter, which reflects white matter damage and is the cranial ultrasound abnormality that best predicts neurodevelopmental dysfunction. We postulated that some of the increased risk of neurodevelopmental problems associated with HOP reflects an increased risk of EL. STUDY DESIGN: We studied 1414 infants weighing 500 to 1500 g who were born at 4 medical centers between 1991 and 1993. The infants had thyroxine blood levels measured during the first weeks of life, at least 1 of 3 cranial ultrasound scans performed at specified postnatal intervals, and their own and their mother's hospital charts reviewed. Infants were classified by whether or not their first thyroxine level placed them in the lowest quartile among all infants in this sample (ie, <67.8 nmol/L, our definition of HOP, equivalent to <5.3 micrograms/dL). RESULTS: After adjusting for such potential confounders as low gestational age and measures of illness severity, infants with HOP had twice the risk of EL as their peers with higher thyroxine levels. CONCLUSION: Our findings are consistent with the hypothesis that a "normal" blood thyroxine level protects infants born near the end of the middle trimester against the risk of cerebral white matter damage.     

Age-related variations in white matter anisotropy in school-age children

Background

Determination of diffusion tensor metrics in typically developing school-age children shows that maturational increases in fractional anisotropy (FA) vary across the brain and that age effects on FA are to increases in axial diffusivity in some regions, to decreases in radial diffusivity in some, and to both increases in axial and decreases in radial diffusivity in others.

Objective

When studying developing white matter (WM) using diffusion tensor imaging (DTI), knowledge of age-related normative tensor metrics is important, as normal variations can mask or mimic disease effects.

Materials and methods

Right-handed English-speaking children (n?=?32) 6–18 years old (mean 11.0) were studied over 31 months, 7 longitudinally. Anisotropy data were analyzed using tract-based spatial statistics; 43 regions showing significant (P?<?0.05) age effects on fractional anisotropy (FA) were analyzed for age effects (r), coefficient of variability (CV), and FA, axial and radial diffusivity. This study was IRB-approved.

Results

The callosal genu and splenium showed the highest FA values, smallest age effects, and lowest between-subject variability. Mean FA was lower and age effects were greatest in the dorsal callosal body. The highest age effects on FA were in the cingulum, centrum semiovale, right corticospinal tract, and right temporal WM. The dorsal callosal body, calcarine WM, superior frontal and temporal gyri, and right corticospinal tract showed the highest CV. Radial diffusivity decreased while axial diffusivity increased in the cingulum, decreased in the optic tracts, and showed minimal or no age effects in most other regions.

Conclusion

Age effects on FA and variability in FA are location-dependant in developing WM.     

晚期早产儿脑白质损伤临床特点及磁共振影像学发现

目的：探讨晚期早产儿脑白质损伤的临床特点及常规磁共振成像（MRI）和弥散加权成像（DWI）影像学特征。方法：总结2005年1月至2008年5月中国医科大学盛京医院收治的519例早产儿资料（277例晚期早产儿,242例早期早产儿）,对其头部常规MRI和DWI特征进行分析。结果：晚期早产儿中,脑白质损伤118例,占脑损伤的71.9%（118/164）,占全部晚期早产儿的42.6%（118/277）。早期早产儿脑白质损伤占脑损伤的69.2%（92/133）,占全部早期早产儿的38.0%（92/242）,晚期早产儿脑白质损伤发生率与早期早产儿相比无明显差异。晚期早产儿脑白质损伤中无明显临床症状者占61.9%（73/118）,重症脑损伤（广泛性及弥漫性脑损伤）早期有明显临床症状者占75%（15/20）。损伤1周内,DWI表现为高信号,T1WI信号正常或稍高信号,伴或不伴T2WI高信号;弥漫性损伤者呈DWI高信号,常规MRI无明显信号改变。结论：脑白质损伤在晚期早产儿亦较常见。重症脑白质损伤患儿早期多有明显的临床表现。DWI在损伤早期的敏感度高于常规MRI。［中国当代儿科杂志,2010,12（5）：321-326］     

Dysmyelination of the cerebral white matter with microdeletion at 6p25

A 6 year old boy presented with mental retardation, hypotonia, abnormal facies, impaired hearing, protuberant eyes, visual impairment, short stature, Axenfeld-Rieger anomaly, a bicuspid aortic valve, and bilateral sensorineural deafness. CT scan of head suggested dysmyelination of the subcortical and periventricular white matter. FISH revealed a subtelomeric microdeletion encompassing both FOXC1 and FOXF2 loci within 6p25. Dysmyelination of the central nervous system has been infrequently described earlier in patients with 6p25 deletion.     

Magnetic resonance imaging and T2 relaxometry of cerebral white matter and hippocampus in children born preterm

The objective of this study was to determine whether intelligence and minor motor impairments in children who are born preterm without major disability are associated with cerebral white matter (CWM) and hippocampal abnormalities on magnetic resonance imaging (MRI). A total of 103 preterm children were studied at age 7 y with detailed magnetic resonance brain scans, including a T2-mapping sequence from which T2 relaxation times of the CWM and hippocampal formations were calculated. All of the children had no major motor disability, attended normal school, and had undergone assessment of IQ and a test for minor motor impairment (MMI). Twenty children had visible lesions on MRI, which were associated with lower IQ and more frequent MMI. Mean (SD) IQ was 90 (14.1). Twenty-five children were shown to have MMI (Movement ABC at below the fifth centile). This group was shown to have significantly longer T2 relaxation times for CWM (mean difference 2.1 ms right, 3.1 ms left) but not the hippocampus than the children without MMI. These differences persisted when only children without visible lesions on scans were considered (mean difference 1.5 ms bilaterally). There was no significant correlation between IQ and T2 relaxation times. Children who are born preterm without subsequent major neurodisability may, in addition to visible lesions on MRI scans, have a diffuse abnormality of CWM, manifest as an increase in T2 relaxation time. This abnormality shows a close correlation with minor motor impairment but not with full-scale IQ.