Diffusion tensor imaging assesses white matter injury in neonates with hypoxic-ischemic encephalopathy

With improvements in care of at-risk neonates, more and more children survive. This makes it increasingly important to assess, soon after birth, the prognosis of children with hypoxic-ischemic encephalopathy. Computed tomography, ultrasound, and conventional magnetic resonance imaging are helpful to diagnose brain injury, but cannot quantify white matter damage. In this study, ten full-term infants without brain injury and twenty-two full-term neonates with hypoxic-ischemic encephalopathy (14 moderate cases and 8 severe cases) underwent diffusion tensor imaging to assess its feasibility in evaluating white matter damage in this condition. Results demonstrated that fractional anisotropy, voxel volume, and number of fiber bundles were different in some brain areas between infants with brain injury and those without brain injury. The correlation between fractional anisotropy values and neonatal behavioral neurological assessment scores was closest in the posterior limbs of the internal capsule. We conclude that diffusion tensor imaging can quantify white matter injury in neonates with hypoxic-ischemic encephalopathy.     

常规MRI正常的新生儿缺氧缺血性脑病弥散张量成像初探

目的研究弥散张量MRI(diffusion-tensor MR imaging,DTI)对于临床诊断为新生儿缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)而常规MRI所见为正常病例的评估能力。方法选择20例常规MRI所见为正常的足月HIE患儿,以10例正常新生儿为对照,分组进行常规MRI、DTI扫描,测定两组新生儿相同感兴趣区(region of interest,ROI)的平均弥散度(mean diffusivity,Da)、分数各向异性(fractional anisotropy,FA)和相对各向异性值(relative anisotropy,RA)。用Student t—test法检验两组患儿各项指标,并观察比较两组新生儿的彩色FA图和彩色编码张量图。结果两组新生儿的Da在侧脑室前角前外侧白质、内囊后肢,放射冠各个感兴趣区均无显著性差异,而FA和RA值各感兴趣区则有明显差异,表现为HIE患儿FA值和RA值的下降,并且Da的高低与孕龄的长短有一定相关性。结论FA和RA是HIE患儿白质损伤或功能障碍的敏感指标,结合彩色FA图和彩色编码张量图可对患儿白质髓鞘的损伤作出较为准确、客观的评价,并可能在今后评估患儿的预后转归方面起重要作用。     

Relationship of EEG sources of neonatal seizures to acute perinatal brain lesions seen on MRI: A pilot study

Even though it is known that neonatal seizures are associated with acute brain lesions, the relationship of electroencephalographic (EEG) seizures to acute perinatal brain lesions visible on magnetic resonance imaging (MRI) has not been objectively studied. EEG source localization is successfully used for this purpose in adults, but it has not been sufficiently explored in neonates. Therefore, we developed an integrated method for ictal EEG dipole source localization based on a realistic head model to investigate the utility of EEG source imaging in neonates with postasphyxial seizures. We describe here our method and compare the dipole seizure localization results with acute perinatal lesions seen on brain MRI in 10 full‐term infants with neonatal encephalopathy. Through experimental studies, we also explore the sensitivity of our method to the electrode positioning errors and the variations in neonatal skull geometry and conductivity. The localization results of 45 focal seizures from 10 neonates are compared with the visual analysis of EEG and MRI data, scored by expert physicians. In 9 of 10 neonates, dipole locations showed good relationship with MRI lesions and clinical data. Our experimental results also suggest that the variations in the used values for skull conductivity or thickness have little effect on the dipole localization, whereas inaccurate electrode positioning can reduce the accuracy of source estimates. The performance of our fused method indicates that ictal EEG source imaging is feasible in neonates and with further validation studies, this technique can become a useful diagnostic tool. Hum Brain Mapp 34:2402–2417, 2013. © 2012 Wiley Periodicals, Inc.     

NSE对新生儿高胆红素血症换血治疗的指导意义

目的通过检测新生儿重症高胆红素血症患儿血清神经元特异性烯醇化酶(NSE)及头颅MRI的检查,早期发现新生儿胆红素脑损伤,以指导积极的换血治疗。方法选择本院2012-11—2014-06收治的新生儿重症高胆红素血症患儿60例与胆红素脑病患儿25例,检测血清NSE及头颅MRI,分析不同胆红素水平下NSE值及头颅MRI的变化,胆红素脑病及MRI有脑损伤的(苍白球信号改变)高胆患儿均进行换血治疗,其余无脑损伤患儿行光疗,复查NSE及MRI。结果重症高胆红素患儿血清NSE均升高,而胆红素脑病患儿升高更明显,差异有统计学意义(P0.05)。60例重症高胆红素血症患儿中发现4例有胆红素脑损害的MRI改变,25例胆红素脑病中发现14例有胆红素脑损伤的MRI改变,换血治疗后24h复查NSE均迅速下降50%以上,而4例MRI均在1月时恢复正常。光疗治疗后的NSE在24h下降30%,与换血治疗相比,差异有统计学意义(P0.05)。结论血清NSE水平结合MRI检查可反映早期脑损伤,有脑损伤患儿NSE值与无脑损伤患儿的NSE值有明显差别,换血治疗后NSE下降程度较光疗更明显。高胆红素血症患儿换血治疗可参考NSE值,以防止后遗症的发生。     

Diffusion-weighted imaging in neonatal cerebral infarction: clinical utility and follow-up

We describe the clinical utility of echo-planar diffusion-weighted imaging in neonatal cerebral infarction. Eight full-term neonates aged 1 to 8 days referred for neonatal seizures were studied. Patients were followed for a mean of 17 months with detailed neurologic examinations at regular intervals. Head computed tomography (CT) and conventional magnetic resonance (MRI) and diffusion-weighted images were obtained. Percent lesion contrast was evaluated for 19 lesions on T2-weighted and diffusion-weighted images. Follow-up conventional MRIs were obtained in seven patients. The findings on diffusion-weighted imaging were correlated with CT and conventional MRI findings as well as with short-term neurodevelopmental outcome. Four patients had focal cerebral infarctions. Four patients had diffuse injury consistent with hypoxic-ischemic encephalopathy. Percent lesion contrast of all 19 lesions was significantly higher on diffusion-weighted images when compared with T2-weighted images. In five patients, there were lesions visualized only with diffusion-weighted imaging. In all patients, there was increased lesion conspicuity and better definition of lesion extent on the diffusion-weighted images compared with the CT and T2-weighted MR images. In seven of eight patients follow-up imaging confirmed prior infarctions. Short-term neurologic outcome correlated with the extent of injury seen on the initial diffusion-weighted imaging scans for all patients. Diffusion-weighted imaging is useful in the evaluation of acute ischemic brain injury and seizure etiology in neonates. In the acute setting, diffusion-weighted imaging provides information not available on CT and conventional MRI. This information correlates with short-term clinical outcome.     

Interdisciplinary Approach to Neurocritical Care in the Intensive Care Nursery

Neurocritical care is a multidisciplinary subspecialty that combines expertise in critical care medicine, neurology, and neurosurgery, and has led to improved outcomes in adults who have critical illnesses. Advances in resuscitation and critical care have led to high rates of survival among neonates with life-threatening conditions such as perinatal asphyxia, extreme prematurity, and congenital malformations. The sequelae of neurologic conditions arising in the neonatal period include lifelong disabilities such as cerebral palsy and epilepsy, as well as intellectual and behavioral disabilities. Centers of excellence have adapted the principles of neurocritical care to reflect the needs of the developing newborn brain, including early involvement of a neurologist for recognition and treatment of neurologic conditions, attention to physiology to help prevent secondary brain injury, a protocol-driven approach for common conditions like seizures and hypoxic-ischemic encephalopathy, and education of specialized teams that use brain monitoring and imaging to evaluate the effect of critical illness on brain function and development.     

Clinical features and neuroradiological findings of mitochondrial pathology in six neonates

OBJECTS: We hoped to itemize the clinical and neuroradiological features of six neonates with mitochondrial disorders. METHODS: We examined a case series of six neonates. The diagnosis of mitochondrial cytopathy was made on the basis of spectrophotometric measurements of respiratory chain enzyme activities in skeletal muscle biopsy specimens. Magnetic resonance (MR) imaging was performed in all cases. CONCLUSIONS: The antenatal onset in five cases and the lack of any symptom-free interval are suggestive of fetal expression of the disease. No specific symptoms were found: arthrogryposis congenita multiplex in one, progressive hepatocellular dysfunction in three, encephalomyelopathy and cardiomyopathy in four. Complex I deficiency was found in three patients, while one patients had a defect of complex IV and the last a combined defect of complexes I and IV. Neuroradiological findings were either cerebral atrophy or white matter abnormalities of the brain stem in all cases but one and gave additional information, because clinical symptoms are not quite specific. The combination of clinical and MRI findings in neonatal cases can rule out hypoxic ischemic encephalopathy, which suggests an additional screening method to look for mitochondrial disorder.     

Neonatal idiopathic cerebral venous thrombosis: an unrecognized cause of transient seizures or lethargy.

Seven neonates who presented with either lethargy (four infants) or seizures (three infants) were found by magnetic resonance (MR) phase imaging to have idiopathic cerebral venous thrombosis (CVT). Examination showed only hypotonia or hyperreflexia. The presence of CVT was suggested by unenhanced cranial computed tomographic (CT) scans. Conventional MR T1- and T2-weighted images often indicated more extensive thromboses than were suggested by cranial CT. In all infants, MR phase imaging confirmed thromboses by establishing absence of blood flow in cerebral veins or sinuses. No infant received anticoagulation. Lethargy slowly resolved and seizures did not recur. Normal development has been observed thus far in brief follow-up. The occurrence of seven infants with idiopathic neonatal CVT within a 3-month period indicates that CVT may be a cause of neonatal seizures or lethargy of unclear cause. MR phase imaging provides a powerful, noninvasive means of confirming the diagnosis. Treatment with anticoagulants does not appear necessary.     

Diffusion MRI abnormalities in pediatric neurological disorders

Diffusion-weighted imaging (DWI) makes it possible to measure early changes in cellular function in the central nervous system. The purpose of this article is to discuss the diagnostic value of diffusion-weighted and diffusion tensor imaging (DTI) in different pediatric cerebral disorders. First, the principles of DWI and DTI are briefly reviewed. The clinical usefulness of these imaging techniques is then discussed using cases with pediatric neurological disorders, such as hypoxic-ischemic encephalopathy in neonates, trauma (shaken baby syndrome), encephalopathy or encephalitis in infants, posterior reversible encephalopathy syndrome and congenital brain anomaly (callosal dysgenesis). In addition, using DTI, we evaluate normal brain development, particularly in the corpus callosum and cortico-spinal tract, and discuss the application of DTI to the study of white matter in the developing brain.     

Hypothermia is correlated with seizure absence in perinatal stroke

Within a single-center prospective cohort study of neonatal encephalopathy involving 315 subjects, 15 neonates were found to have a focal stroke on magnetic resonance imaging. These 15 patients were matched on the basis of gender and degree of encephalopathy to 30 neonates without stroke from the same cohort. On Bayley Scales of Infant Development, the stroke group had Mental Development Index scores that were 1.7 standard deviations lower compared with controls (P = .007). This association was no longer seen after adjustment for the presence of neonatal seizures (P = .11). Of the 15 patients with stroke, 5 had been treated with hypothermia. None of these 5 had seizures in the neonatal period, compared with 7 of the untreated 10. This is the first human study to demonstrate a potential treatment effect of therapeutic hypothermia on perinatal stroke. It was also shown that seizures are associated with worse cognitive outcomes for stroke that presents with encephalopathy.     

Neonatal diffusion-weighted MR imaging: relation with histopathology or follow-up MR examination

PURPOSE: Diffusion-weighted imaging (DWI) has become a standard method for early evaluation of stroke in adults, but its value in neonates is less well established. In this study neonatal DWI was compared with histopathology in those patients who died, or with sequelae seen on a second MR in the surviving neonates. PATIENTS AND METHODS: DWI was performed in 2 groups.Group 1: seven neonates who died and had a post-mortem ex-amination (perinatal asphyxia [n=5], symptomatic hypoglycemia [n= 11, periventricular leukomalacia [n= 1]). Group 2: six surviving neonates with a second MR examination at three months of age (perinatal asphyxia [n= 21, neonatal stroke[n= 3], meningo-encephalitis [n= 1]). RESULTS: In group l neonatal DWI showed more extensive involvement than conventional MRI in 6 out of 7 patients. These changes were less extensive,however, than seen post-mortem by histopathology in 5 out of 7. In group 2 neonatal DWI showed more extensive involvement than conventional MRI in 2 out of 6; 4 out of 6, however, showed less extensive cystic evolution on follow-up MRI at 3 months than expected from neonatal imaging. CONCLUSION: There was a good relation between hyperintense areas on DWI and areas of cytotoxic edema and neuronal damage on histopathology. In the survivors a second MRI showed cystic evolution in all, but the volume of the cysts was smaller than expected on the basis of the neonatal DWI findings.     

Quantitative cranial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy

The volume of acute injury detected by diffusion-weighted imaging and quantitative brain growth on serial cranial magnetic resonance imaging was not previously used to predict neurodevelopmental outcomes in infants with neonatal hypoxic-ischemic encephalopathy treated with head cooling. Our longitudinal study involved 16 head-cooled term infants with hypoxic-ischemic encephalopathy who underwent early and follow-up cranial magnetic resonance imaging and follow-up neurologic evaluations, out of 105 infants who received therapeutic hypothermia. The volume of acute injury was measured on initial cranial magnetic resonance imaging, using diffusion-weighted images. Total brain volumes were measured in both early and follow-up magnetic resonance imaging studies. Acute injury volume in the corpus callosum >0.5 cm(3) was associated with developing epilepsy (odds ratio, 20; 95% confidence interval, 1.01-1059.6; P = 0.013). Follow-up whole brain volume was reduced in those with unfavorable outcomes (i.e., epilepsy, cerebral palsy, and delayed developmental milestones), compared with infants without all three outcomes. Although acute brain injury volume and brain growth measurements may be useful predictors of outcomes in neonatal hypoxic-ischemic encephalopathy, the evolution of brain injury in these infants has yet to be fully understood and should be studied prospectively.     

Thermal therapies in interventional MR imaging. Cryotherapy

Cryotherapy of the brain is an old and well-established technique of functional and resective neurosurgery. With the use of modern imaging techniques such as MR imaging, which is ideally suited for diagnosis, planning, and monitoring of an ablation procedure, cryotherapy can become a modern alternative to other ablation techniques. In contrast to hyperthermal ablation tools such as laser or radiofrequency ablation, cryotherapy has specific potentials. First and most importantly, the freezing process ideally can be precisely monitored by MR imaging during the procedure without any specific temperature-sensitive pulse sequence. As shown in the experimental study, several techniques including conventional gradient echo sequences, ultrafast subsecond MR sequences, and MR fluoroscopy, are suited for monitoring the freezing process. Furthermore, the volume of the damaged tissue, as imaged by MR imaging, does not increase after completion of the ablation procedure. The extension of the ice corresponds well to the final, histologically confined necrosis and allows a high predictability of the resulting necrosis. Although not yet in clinical use, the combination of minimally invasive modern cryotherapy devices and ultrafast interventional MR techniques offer a promising alternative to other ablation techniques. In addition, it holds great promise for minimally invasive neurologic procedures in the near future. Further technical modifications and clinical studies, however, are necessary to establish the potential of this new treatment option.     

Diffusion MR imaging: an important tool in the assessment of brain tumors

For over 20 years, conventional MR imaging has been used for assessing brain tumors. However, conventional MR imaging tends to underestimate the extent of the tumor, perhaps leading to suboptimal treatment. New MR imaging tools have been widely used to determine the grade, heterogeneity, and extent of brain tumors. Diffusion-weighted imaging has been studied extensively, helping in tumor grading, differential diagnosis, and postoperative evaluation. Diffusion tensor imaging can apparently delineate more accurately the tumor versus the infiltrating tumor between the peritumoral edema and the normal brain parenchyma. This article shows the main clinical applications of these sequences.     

Neurophysiological aspects of neonatal seizures

Recently, amplitude-integrated EEG (aEEG) has been increasingly used and proved useful in neonatal intensive care units (NICU) for the management of neonatal seizures. It does not replace, but is supplementary to standard EEG. This article reviews some of findings obtained with standard EEGs, and tries to interpret them with recent findings in the field of basic science. Seizures mainly occur in active-REM sleep in neonates. This is in sharp contrast to those in older children and adults, in whom epileptic seizures occur mainly in NREM sleep. This may be explained by neurotransmitter effects on sleep mechanisms of the neonatal brain that are different from those of older individuals. When all clinical seizures have no electrical correlates, they are non-epileptic, but when the correlation between clinical seizures and frequent electrical discharges are inconsistent, they should rather be considered epileptic, reflecting progression of status epilepticus causing electro-clinical dissociation. Electro-clinical dissociation is not a characteristic of neonatal seizures per se, but a feature of prolonged status epilepticus in adults as well as children. It occurs when prolonged status epilepticus itself causes a progressively severe encephalopathy, or when status occurs in the presence of a severe underlying encephalopathy. In neonates without pre-existing brain damage, frequent seizures per se may cause mild depression characterized by the loss of high voltage slow patterns, an important constituent of slow wave sleep reflecting cortico-cortical connectivity. Mild depression only in the acute stage is not associated with neurological sequelae, but previously damaged brain may be more vulnerable than normal brain.     

Neonatal seizures: treatment practices among term and preterm infants

Neonatal seizures are common clinical conditions in both term and preterm neonates, yet no clinical management guidelines for direct care exist. We surveyed 193 international neurologists, neonatologists, and specialists in neonatal neurology or neonatal neurocritical care to assess management practices for seizures in preterm and term neonates. We found high reported rates of electroencephalogram and amplitude-integrated electroencephalogram (aEEG) monitoring to detect neonatal seizures, prevalent use of older anticonvulsant agents, and high rates of neuroimaging. Overall, responses were similar for term and preterm neonates. However, term neonates were likelier to be more heavily investigated, with higher use of magnetic resonance imaging and of electroencephalogram and aEEG monitoring of at-risk neonates. Continuous monitoring and cranial imaging of neonatal seizures now comprise the standard of care in many centers, although management practices vary widely. Early recognition and management of neonatal seizures and possible underlying injury may lead to increased opportunities for stopping seizures, protecting the brain, and improving developmental outcomes in at-risk neonates. The need for collaboration among neonatologists and neurologists is urgent, to address gaps in knowledge regarding management of neonatal seizures in term and preterm neonates.     

Timing of neonatal seizures and intrapartum obstetrical factors

One hundred ninety-three neonates with seizures were available on a neonatal seizure database, which included intrapartum and neonatal factors such as labor duration, fetal heart rate abnormalities, cord blood gas values, Apgar scores and clinical signs of encephalopathy. Regression analyses (analysis of variance) were performed on the entire cohort as well as specific subsets of neonates (eg, neonatal encephalopathy vs no encephalopathy) to assess the relationship between seizure timing and intrapartum/neonatal factors. Seizures were noted earlier for the encephalopathic group than for the nonencephalopathic group. No significant differences were noted for any intrapartum or neonatal factors. Timing of neonatal seizures, with or without an encephalopathy occurs within the first 2 days after birth and is independent of selected intrapartum and neonatal factors, underscoring recent task force recommendations concerning neonatal encephalopathy. Factors other than intrapartum events more likely contribute to the encephalopathic repertoire of the newborn, including seizures.     

Perinatal asphyxia: Timing and mechanisms of injury in neonatal encephalopathy

This article summarizes the recent medical literature regarding perinatal asphyxia with respect to timing and mechanisms of injury for neonates who were clinically diagnosed with an encephalopathy in the newborn period. Multiple mechanisms of injury are reviewed, including genetic vulnerability, acquired inflammatory responses, and clotting defects that can lead to ischemic-induced brain damage. Before effective treatments for fetal and neonatal brain disorders can be developed, accurate and timely diagnoses of fetal or neonatal brain injury must be achieved. Specific subsets of children can then benefit from neuroprotective strategies that can target the specific developmental aspects of brain adaptation or plasticity relative to the specific etiology and timing of injury after asphyxia.     

Neurodiagnostic Techniques in Neonatal Critical Care

This article reviews recent advances in the neurodiagnostic tools available to clinicians practicing in neonatal critical care. The advent of induced mild hypothermia for acute neonatal hypoxic-ischemic encephalopathy in 2005 has been responsible for renewed urgency in the development of precise and reliable neonatal neurodiagnostic techniques. Traditional evaluations of bedside head ultrasounds, head computed tomography scans, and routine electroencephalograms (EEGs) have been upgraded in most tertiary pediatric centers to incorporate protocols for MRI, continuous EEG monitoring with remote bedside access, amplitude-integrated EEG, and near-infrared spectroscopy. Meanwhile, recent studies supporting the association between placental pathology and neonatal brain injury highlight the need for closer examination of the placenta in the neurodiagnostic evaluation of the acutely ill newborn. As the pursuit of more effective neuroprotection moves into the “hypothermia plus” era, the identification, evaluation, and treatment of the neurologically affected newborn in the neonatal intensive care unit has increasing significance.     

Brain MRI findings in acute hepatic encephalopathy in liver transplant recipients

Acute hepatic encephalopathy has significant morbidity and mortality in liver transplant recipients unless it is promptly treated. We evaluated the brain magnetic resonance (MR) imaging findings associated with acute hepatic encephalopathy in transplant recipients. We retrospectively reviewed the clinical and imaging data and outcomes of twenty-five liver transplant patients (16 male; mean age, 49.3 years) with clinically diagnosed acute hepatic encephalopathy and forty liver transplant patients (20 males; mean age, 45.5 years) without neurological symptoms suggestive of hepatic encephalopathy at our institution. Bilateral symmetric hyperintensities of the insular cortex and cingulate gyrus were observed in twenty-one patients (84.00%), bilateral symmetric extensive increased cortical signal intensity (involving two or more regions) was observed in 72.00% of the patients, leptomeningeal enhancement in 73.68%, and visualization of prominent venules in 52.00%. The most common symptom at diagnosis was rigidity (n = 14), and the plasma ammonia levels ranged from 68.63 to 192.16 μmol/L. After active treatment, 17 patients gradually recovered, four patients suffered from mild or moderate neurologic deficits, and four patients with widespread brain edema died. The specific brain MR imaging features were bilateral symmetric increased cortical signal intensity, especially in the insular cortex and cingulate gyrus, leptomeningeal enhancement, visualization of the prominent venules, and widespread brain edema. These features may indicate poor prognosis and should alert radiologists to the possibility of acute hepatic encephalopathy in liver transplant recipients and encourage clinicians to prepare appropriate treatment in advance.