Predictive value of neonatal MRI with respect to late MRI findings and clinical outcome. A study in infants with periventricular densities on neonatal ultrasound

PURPOSE: The aim of this study was to correlate hypoxic-ischemic white matter damage on neonatal MRI with MRI appearance and neurological outcome at the age of 1 1/2 years. PATIENTS AND METHODS: A sequential cohort of infants with periventricular densities on neonatal ultrasound was studied with neonatal MRI. Images of 46 infants with a mean gestational age of 31 weeks were obtained at a mean age of 20 days after birth and at 1 1/2 years. To establish agreement between the neonatal and follow-up MRI (general, motor, and visual scores), the weighted Cohen's kappa test was used. To establish the predictive power of neonatal MRI with respect to the neurologic indices at the age of 1 1/2 years, the sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: There was a moderately good to good agreement between the general, motor, and visual neonatal and follow-up MRI scores: weighted kappa = 0.59 (95% CI: 0.44 - 0.74), 0.82 (95% CI: 0.72 - 0.93), and 0.70 (95% CI: 0.56 - 0.84), respectively. Neonatal MRI scores provided a good prediction of the three neurological outcome measures (developmental delay, cerebral palsy, and cerebral visual impairment): sensitivity, specificity, and predictive values were high, with little difference between the three MRI scores. The 32 patients with (nearly) normal neonatal MRI scores were neurologically (nearly) normal at 1 1/2 years on all three outcome measures, whereas 8 patients with seriously abnormal neonatal MRI scores were neurologically abnormal at 1 1/2 years on all three outcome measures. CONCLUSION: Neonatal MRI is able to predict the precise localization and size of perinatal leukomalacia on follow-up MRI and provides a good prediction of neurological outcome at 1 1/2 years.     

Quantitative DTI assessment of periventricular white matter changes in neonatal meningitis

Neonatal meningitis is one of the important causes of infant mortality and morbidity. Periventricular white matter of neonatal brain is known to be vulnerable to oxidative and hypoxic/ischemic injury secondary to neuro-infections. The aim of this study was to assess periventricular white matter damage in neonatal bacterial meningitis using diffusion tensor imaging (DTI). DTI was performed in 7 age/sex matched controls and 14 neonates with proven bacterial meningitis at the time of diagnosis and after 3 weeks of antibiotic treatment. Region of interest were placed on periventricular white matter to quantify fractional anisotropy (FA) and mean diffusivity (MD). Based on the clinical prognosis and conventional MRI, patients were grouped into those with normal and with abnormal outcome. Compared to controls significantly decreased FA values were observed in entire periventricular white matter except for left parietal white matter in patients with abnormal outcome. Even in those with normal outcome significant decrease in FA values were observed in right parietal and bilateral occipital white matter compared to controls. Decreased FA values in the periventricular white matter regions in neonatal meningitis confirm microstructural white matter injury.     

Pathogenesis of periventricular white matter hemorrhages in preterm infants

Periventricular white matter hemorrhage (PWMH) was frequently found in very low-birth weight infants with perinatal asphyxia or respiratory distress. Primary PWMH with or without intraventricular rupture was found at the deep arterial borderzones of the frontal or occipital lobes. The ischemic tissue damage induced by hypoperfusion may be a predisposing factor for PWMH. However, the high incidence of visceral intravascular thrombi and the fan-shaped appearance of hemorrhage suggested venous hemorrhagic infarction. Venous thrombosis with coagulopathy may be an important factor for the pathogenesis of PWMH.     

Serial diffusion tensor imaging detects white matter changes that correlate with motor outcome in premature infants

The objective of the study was to assess predictive value of serial diffusion tensor MRI (DTI) for the white matter injury and neurodevelopmental outcome in a cohort of premature infants. Twenty-four infants less than 32 weeks' gestation were stratified to a control group (n = 11), mild brain injury with grades 1-2 of intraventricular hemorrhage (n = 6) and severe brain injury with grades 3-4 intraventricular hemorrhage (n = 4). Serial DTI studies were performed at around 30 and 36 weeks' gestation. Fractional anisotropy (FA) and apparent diffusion coefficient were calculated. Twelve infants were followed up for developmental outcome. Developmental testing was performed with the Bayley Scales of Infant Development to obtain psychomotor index (Performance Developmental Index). Apparent diffusion coefficient was higher in the severe injury group at the second MRI in the central and occipital white matter, and corona radiata; FA was lower in optic radiation compared to controls. Performance Developmental Index score correlated with FA on the scan taken at the 30th week and inversely with the change of FA between scans in internal capsule and occipital white matter. A low value of FA at 30 weeks and a higher change of FA predicted less favorable motor outcome at 2 years and suggests that early subtle white matter injury can be detected in premature infants even without obvious signs of injury.     

Vasoreactivity in patients with periventricular white matter lucency

OBJECTIVES: Cerebral hypoperfusion has been evidenced in patients with periventricular white matter lucency (PWML), however, our knowledge is limited regarding vasoreactivity (VR) changes in these patients. Therefore, we compared the cerebral blood flow velocity (CBFV) responses during different vasoregulatory challenges in healthy volunteers, to those in patients with PWML. MATERIAL AND METHODS: In 20 patients with PWML and in 20 healthy volunteers the VR of the middle cerebral artery (MCA) system was measured by analyzing the changes of CBFV during different stimulation paradigms (ventilation, tilting and acetazolamide tests). During transcranial Doppler (TCD) registration the systemic blood pressure, the expiratory partial CO(2) pressure (pCO(2)) and the electroencephalograph (EEG) were monitored. RESULTS: The relative velocity change was significantly smaller in the PWML group than in the normal control group during hypercapnia (16 +/- 12% vs 32 +/- 17%; P < 0.001) and this finding was confirmed by assessment of pCO(2)-corrected velocity change (4.7 +/- 3.7 cm/s/kPa vs 18.4 +/- 6.8 cm/s/KPa; P < 0.001). Although CBFV measurements during acetazolamide test tended to support these findings, the changes of other parameters measured did not reach the level of significance. One patient showed considerable orthostatic reaction (mean arterial blood pressure decrease by 70 mmHg) but it was not associated with significant changes in CBFV. CONCLUSION: Patients with PWML showed an impaired VR in the MCA flow territory supporting the concept of the microangiopathic origin of leukoaraiotic changes.     

早产儿脑白质损伤早期相关高危因素

目的 分析早产儿脑白质损伤(WMD)早期相关高危因素.方法 选取郑州大学第二附属医院2018-10—2019-05住院的210例早产儿,根据出生后2周内头颅磁共振结果有无异常分为WMD组及对照组.对比2组患儿在围生期的情况及检查结果,进行单因素分析,对单因素分析中的显著因素进行多因素Logistic回归分析.结果 21...     

Predictive value of EEG in neonates with periventricular leukomalacia

The aim of this study was to evaluate whether EEG (i.e. positive Rolandic sharp waves) can be used to predict neurodevelopment in newborn infants with periventricular leukomalacia and compare the predictive value with that of MRI. A sequential cohort of neonates (n=45; 33 males, 12 females; mean gestational age 31.2 weeks, SD 2.7, range 27 to 37.8 weeks; mean birthweight 1592 g, SD 601 g) with periventricular hyperechogenicities on cranial ultrasound was recruited for this study. EEGs were analyzed for positive Rolandic sharp waves. Neurodevelopment was evaluated at the ages of 12 and 18 months. In the whole group the probability of a poor outcome was 24% and the probability of any impairment was 33%. If the number of positive Rolandic sharp waves was no more than 0.1 per minute, the probability of a poor outcome was reduced to 9% (95% confidence interval [95%CI] 2 to 27%) and the probability of any impairment was reduced to 13% (95%CI 4 to 32%). In all infants with more than 0.1 positive Rolandic sharp waves per minute the probability of a poor outcome was 41% (95%CI 23 to 61%) and of any impairment was 55% (95%CI 34 to 73%). In these infants MRI identified infants with a poor outcome with a sensitivity of 1.00 (95%CI 0.70 to 1.00) and a specificity of 0.92 (95%CI 0.67 to 0.99), and infants with any impairment with a sensitivity of 0.83 (95%CI 0.55 to 0.95) and a specificity of 1.00 (95%CI 0.72 to 1.00). Results suggest that if an EEG of an infant with periventricular leukomalacia contains no more than 0.1 positive Rolandic sharp waves per minute the probability of a normal or mildly delayed development is high (0.91, 95%CI 0.73 to 0.98). MRI enhances the accuracy of the outcome prediction slightly; however, owing to a wide confidence interval, this advantage is negligible. However, if the frequency of the positive Rolandic sharp waves exceeds 0.1per minute, MRI can significantly enhance the precision of the prediction of outcome.     

Melatoninergic neuroprotection of the murine periventricular white matter against neonatal excitotoxic challenge.

Periventricular leukomalacia is one of the main causes of cerebral palsy. Perinatal white matter lesions associated with cerebral palsy appears to involve glutamate excitotoxicity and excess free radical production. When injected intracerebrally into newborn mice, the glutamatergic analog ibotenate induces white matter cysts mimicking human periventricular leukomalacia. Melatonin acts on specific receptors. It also exhibits intrinsic free radical scavenging properties. The goal of the present study is to determine whether melatonin can protect against excitotoxic lesions induced by ibotenate in newborn mice. Mice that received intraperitoneal melatonin had an 82% reduction in size of ibotenate-induced white matter cysts when compared with controls. Although melatonin did not prevent the initial appearance of white matter lesions, it did promote secondary lesion repair. Axonal markers supported the hypothesis that melatonin induced axonal regrowth or sprouting. The protective effects of melatonin were suppressed by coadministration of luzindole, a melatonin receptor antagonist. Forskolin, an adenylate cyclase activator, prevented the protective effects of melatonin; inhibitors of protein kinase C and mitogen-associated protein kinase had no detectable effect. Melatonin and derivatives that block cAMP production through activation of melatonin receptors could represent new avenues for treating human periventricular leukomalacia.     

CT and MRI rating of white matter changes

The impact of white matter changes (WMC) detectable on CT or MRI on various diseases like ischemic stroke and intracerebral hemorrhage and their association with cognitive impairment was and still is under debate. To assess WMC in a qualitative and/or semiquantitative fashion rating scales have been developed. For MRI most widely used scales are the scales of Manolio, Fazekas, Schmidt, and Scheltens. Most recently a new scale extending earlier suggestions has been introduced by Wahlund et al. applicable for both CT and MRI. This article will review strengths and weaknesses of these rating scales and will discuss further requirements and future perspectives.     

Gray matter injury associated with periventricular leukomalacia in the premature infant

Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that subacute and/or chronic gray matter lesions are increased in incidence and severity in PVL cases compared to non-PVL cases at autopsy. Forty-one cases of premature infants were divided based on cerebral white matter histology: PVL (n = 17) with cerebral white matter gliosis and focal periventricular necrosis; diffuse white matter gliosis (DWMG) (n = 17) without necrosis; and “ Negative” group (n = 7) with no abnormalities. Neuronal loss was found almost exclusively in PVL, with significantly increased incidence and severity in the thalamus (38%), globus pallidus (33%), and cerebellar dentate nucleus (29%) compared to DWMG cases. The incidence of gliosis was significantly increased in PVL compared to DWMG cases in the deep gray nuclei (thalamus/basal ganglia; 50–60% of PVL cases), and basis pontis (100% of PVL cases). Thalamic and basal ganglionic lesions occur almost exclusively in infants with PVL. Gray matter lesions occur in a third or more of PVL cases suggesting that white matter injury generally does not occur in isolation, and that the term “perinatal panencephalopathy” may better describe the scope of the neuropathology. Statement of financial support: CRP is supported by KO8 NS049090 from NINDS. This study was supported by grants from NINDS (PO1-NS38475) and NICHD (Children’s Hospital Mental Retardation Research Center) (P30-HD18655).     

MRI signal changes in the white matter after corpus callosotomy

Magnetic resonance imaging (MRI) changes reported after corpus callosotomy include hyperintensity in the corpus callosum, perifalcine hyperintensity caused by surgical retraction, and acute changes associated with surgical complications. The authors have observed MRI signal changes in the cerebral white matter of corpus callosotomy patients that are separate from the sectioned callosum and not clearly related to surgical manipulation or injury. Brain MRI scans were retrospectively reviewed in 25 of 38 patients who underwent anterior, posterior, or total callosotomy for refractory seizures between 1988 and 1995. Nine patients had signal changes in the cerebral white matter on postoperative MRI. Six of these patients had preoperative MRI studies available for comparison, and none of the white matter signal abnormalities were evident preoperatively. T2 prolongation or hyperintensity on proton-density images was observed in areas including the centrum semiovale, forceps major, and forceps minor. Three patients had signal changes that had distinct borders extending only to the posterior limit of the callosotomy. MRI signal changes in the cerebral white matter after corpus callosotomy have not been previously reported and may represent distant effects of callosal section. Wallerian degeneration occurring in the neuronal processes cut during surgery could account for the signal changes.     

Comparison of MRI white matter changes with neuropsychologic impairment in Cockayne syndrome.

The neuropsychologic function and white matter changes observed on magnetic resonance imaging (MRI) in Cockayne syndrome were studied. MRI with T2-weighted sequences revealed periventricular hyperintensity and white matter hyperintensity in all 3 Cockayne syndrome patients examined; in contrast, 8 age-matched controls had no periventricular or white matter hyperintensity. MRI scans were graded according to the severity of periventricular or white matter hyperintensity using a scale applied to an elderly patient population. There was no difference in the severity of MRI white matter changes in these 3 Cockayne syndrome patients, 2 of whom had severe neuropsychologic functions and one a relatively milder one. There was no correlation between neuropsychologic impairment and MRI white matter changes.     

Extent of altered white matter in unilateral and bilateral periventricular white matter lesions in children with unilateral cerebral palsy

AimsTo investigate the extent of white matter damage in children with unilateral cerebral palsy (UCP) caused by periventricular white matter lesions comparing between unilateral and bilateral lesions; and to investigate a relationship between white matter microstructure and hand function.Methods and proceduresDiffusion MRI images from 46 children with UCP and 18 children with typical development (CTD) were included. Subjects were grouped by side of hemiparesis and unilateral or bilateral lesions. A voxel-wise white matter analysis was performed to identify regions where fractional anisotropy (FA) was significantly different between UCP groups and CTD; and where FA correlated with either dominant or impaired hand function (using Jebsen Taylor Hand Function Test).Outcomes and resultsChildren with unilateral lesions had reduced FA in the corticospinal tract of the affected hemisphere. Children with bilateral lesions had widespread reduced FA extending into all lobes. In children with left hemiparesis, impaired hand function correlated with FA in the contralateral corticospinal tract. Dominant hand function correlated with FA in the posterior thalamic radiations as well as multiple other regions in both left and right hemiparesis groups.Conclusions and implicationsPeriventricular white matter lesions consist of focal and diffuse components. Focal lesions may cause direct motor fibre insult resulting in motor impairment. Diffuse white matter injury is heterogeneous, and may contribute to more global dysfunction.What this paper adds

• ⿢Focal white matter alterations are observed in the corticospinal tract in UCP with unilateral white matter lesions
• ⿢Diffuse white matter alterations throughout all cerebral lobes are observed in UCP with bilateral white matter lesions
• ⿢Fractional anisotropy in the posterior thalamic radiations correlates with dominant hand function

     

Impact of white matter changes on activities of daily living in mild to moderate dementia

The association between white matter changes and activities of daily living (ADL) in a large, well-defined cohort of patients with mild-to-moderate dementia (either Alzheimer's disease or subcortical vascular dementia) were investigated. A total of 289 patients were divided into three groups (140 mild, 99 moderate, and 50 severe) depending on the degree of white matter changes as indicated on brain magnetic resonance image scans. Further, we analyzed the three groups' performances on basic and instrumental ADL. The degree of white matter changes was associated with greater age, hypertension, previous history of stroke, higher Hachinski Ischemic Score, worse global cognitive and functional status, and an increased impairment of basic ADL and instrumental ADL. The increased impairment with regard to the severe group's performance on both the basic and instrumental ADL remained significant after adjustment for age and hypertension. Tasks involving physical activities were most significant. This was the first study investigating the association between white matter changes and ADL in a large, well-defined dementia cohort. The present study suggests that severe white matter changes may be associated with higher impairment on both basic and instrumental ADL.     

Defective motion processing in children with cerebral visual impairment due to periventricular white matter damage

Aim We sought to characterize visual motion processing in children with cerebral visual impairment (CVI) due to periventricular white matter damage caused by either hydrocephalus (eight individuals) or periventricular leukomalacia (PVL) associated with prematurity (11 individuals). Method Using steady‐state visually evoked potentials (ssVEP), we measured cortical activity related to motion processing for two distinct types of visual stimuli: ‘local’ motion patterns thought to activate mainly primary visual cortex (V1), and ‘global’ or coherent patterns thought to activate higher cortical visual association areas (V3, V5, etc.). We studied three groups of children: (1) 19 children with CVI (mean age 9y 6mo [SD 3y 8mo]; 9 male; 10 female); (2) 40 neurologically and visually normal comparison children (mean age 9y 6mo [SD 3y 1mo]; 18 male; 22 female); and (3) because strabismus and amblyopia are common in children with CVI, a group of 41 children without neurological problems who had visual deficits due to amblyopia and/or strabismus (mean age 7y 8mo [SD 2y 8mo]; 28 male; 13 female). Results We found that the processing of global as opposed to local motion was preferentially impaired in individuals with CVI, especially for slower target velocities (p=0.028). Interpretation Motion processing is impaired in children with CVI. ssVEP may provide useful and objective information about the development of higher visual function in children at risk for CVI.     

Microglial reaction in axonal crossroads is a hallmark of noncystic periventricular white matter injury in very preterm infants

Disabilities after brain injury in very preterm infants have mainly been attributed to noncystic periventricular white matter injury (PWMI). We analyzed spatiotemporal patterns of PWMI in the brains of 18 very preterm infants (25-29 postconceptional weeks [pcw]), 7 preterm infants (30-34 pcw), and 10 preterm controls without PWMI. In very preterm infants, we examined PWMI in detail in 2 axonal crossroad areas in the frontal lobe: C1 (lateral to the lateral angle of the anterior horn of the lateral ventricle, at the exit of the internal capsule radiations) and C2 (above the corpus callosum and dorsal angle of the anterior horn). These brains had greater microglia-macrophage densities and activation but lesser astroglial reaction (glial fibrillary acidic protein and monocarboxylate transporter 1 expression) than in preterm cases with PWMI. In preterm infants, scattered necrotic foci were rimmed by axonal spheroids and ionized calcium binding adaptor molecule 1-positive macrophages. Diffuse lesions near these foci consisted primarily of hypertrophic and reactive astrocytes associated with fewer microglia. No differences in Olig2-positive preoligodendrocytes between noncystic PWMI and control cases were found. These data show that the growing axonal crossroad areas are highly vulnerable to PWMI in very preterm infants and highlight differences in glial activation patterns between very preterm and preterm infants.     

Cerebral hemodynamics during early neonatal period in preterm infants with periventricular leukomalacia

We prospectively investigated the relation among cerebral blood flow, periventricular leukomalacia (PVL) and hypocarbia using Doppler ultrasonography in 53 preterm infants with gestational age between 27 and 34 weeks who required mechanical ventilation during the first 72 h of life. Cerebral blood flow of pericallosal artery was assessed by Doppler ultrasonography at the first and the third day of life. Mean velocity (MV) and Resistance index (RI) of anterior cerebral artery were calculated from the data obtained by Doppler ultrasonography. The diagnosis of PVL was made in 12 infants on the basis of the results of ultrasonography and MRI. Hypocarbia was judged as positive when both arterial blood gas analyses before and after the ultrasonography revealed PaCO(2) values < 25 mmHg. On the first day of life, RI was 0.62 +/- 0.022 in infants with PVL and 0.71 +/- 0.014 in those without PVL. On the third day of life, RI was 0.60 +/- 0.032 in infants with PVL and 0.66 +/- 0.013 in those without PVL. There was a significant difference in RI between the two groups at either point. MV was not significantly different between the two groups at either point. There was no significant difference in RI or MV between infants with and without hypocarbia at either point. RI was significantly lower in infants with PVL during the first 72 h of life, which is suggestive of vasoparalysis in such infants at the level of major cerebral arteries. However, RI or MV was no different between infants with and without hypocarbia.     

Cerebrospinal fluid tau protein and periventricular white matter lesions in patients with mild cognitive impairment: implications for 2 major pathways

BACKGROUND: Mild cognitive impairment (MCI) may be a heterogeneous condition rather than a uniform disease entity. OBJECTIVE: To develop reliable tools that aid in identifying patients at risk of developing Alzheimer disease (AD) among heterogeneous populations with MCI to maximize the benefits of emerging therapies for AD. DESIGN: A 2-year prospective study. SETTING: Clinical follow-up in an outpatient memory clinic. PATIENTS: Seventy-two consecutive older patients with memory complaints. MAIN OUTCOME MEASURES: Cerebrospinal fluid tau levels, severity of periventricular and deep white matter lesions, silent brain infarction on magnetic resonance imaging, plasma homocysteine levels, apolipoprotein E genotype, and other vascular risk factors were assessed at baseline. RESULTS: Fifty-seven patients were diagnosed as having amnestic MCI. Forty-one patients with (AD-converted MCI group) or without (progressive MCI group) conversion to dementia and AD progressed over time, whereas the other 16 patients remained cognitively stable (stable MCI group). The stable MCI group was characterized by normal cerebrospinal fluid tau levels and a high grade of periventricular white matter lesions (PWMLs). The progressive MCI and AD-converted MCI groups had increased cerebrospinal fluid tau levels and low grades of PWMLs. A logistic regression model showed that age was significantly associated with developing PWMLs (P =.03; odds ratio, 1.15; 95% confidence interval, 1.0-1.3). CONCLUSIONS: Tau-related AD pathologic conditions and possibly ischemic PWMLs represent 2 major etiologies in the development of MCI, reflecting heterogeneity in the clinical progression. Because the progressive type of MCI may be a primary target of clinical trials that aim at secondary prevention of dementia, these patients should be identified by appropriate biomarkers and neuroimaging techniques.