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ORIGINAL ARTICLE |
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Year : 2022 | Volume
: 35
| Issue : 2 | Page : 626-632 |
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Role of MRI in the prognosis of hypoxic–ischemic encephalopathy
Adel El Wakeel, Aisha S. M. Saad, Rehab Habib
Department of Diagnostic Radiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
Date of Submission | 25-Sep-2021 |
Date of Decision | 04-Nov-2021 |
Date of Acceptance | 07-Nov-2021 |
Date of Web Publication | 27-Jul-2022 |
Correspondence Address: Aisha S. M. Saad Shebin Elkom, Menoufia Egypt
Source of Support: None, Conflict of Interest: None | Check |
DOI: 10.4103/mmj.mmj_179_21
Background Neonatal encephalopathy is a heterogeneous syndrome characterized by signs of central nervous system dysfunction in newborn infants. The main cause of neonatal encephalopathy can be broadly divided into perinatal asphyxia [hypoxic–ischemic encephalopathy (HIE)], perinatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital neonatal central nervous system infections, and severe birth trauma. Objectives To highlight the predictive value of MRI as a safe and superior neuroimaging technique in cases of HIE. Patients and methods This progressive study was conducted on 30 neonates with HIE referred to the Radiology Department at Menoufia University Hospitals for advanced magnetic resonance techniques assessment during the period from July 2019 to December 2020. The study received the approval of Ethics Committee of Faculty of Medicine, Menoufia University. A written informed consent was taken from the parents or caregivers and written informed consent was obtained from them. Results Apparent diffusion coefficient (ADC) value was significantly increased with hypertonia (1.75 ± 1.21), hypotonia (1.52 ± 1.51), and MRI than flaccid (0.86 ± 0.67). There was no statistically significant relation between ADC value with time of birth, causes of admission, Apgar score, time of birth at 5 min, Tendon reflex, seizures, periventricular leukomalacia, and intraventricular hemorrhage. Conclusion MRI findings were significantly related with diffusion-weighted (DW) and ADC value. MRI findings indicated that periventricular leukomalacia and basal ganglia ischemia were significantly related with DW. Moreover, it was noted that MRI is a very efficient tool in evaluating morphometric HIE. It's noninvasiveness and no exposure to ionizing radiation is an added advantage. However, experience and understanding of the principles are essential for accurate diagnosis. Also, DW and ADC values may add value to routine MRI examination. However, there is limitation in our study as regards the small number of cases, lack of clinical data, and long-term follow-up of cases.
Keywords: apparent diffusion coefficient, magnetic resonance, neonatal encephalopathy
How to cite this article: El Wakeel A, Saad AS, Habib R. Role of MRI in the prognosis of hypoxic–ischemic encephalopathy. Menoufia Med J 2022;35:626-32 |
Introduction | | |
Neonatal encephalopathy is a heterogeneous syndrome characterized by signs of central nervous system dysfunction in newborn infants. Clinical suspicion of neonatal encephalopathy should be considered in any infant exhibiting an abnormal level of consciousness, seizures, tone and reflex abnormalities, apnea, aspiration, feeding difficulties, and an abnormal hearing screen[1]. The main cause of neonatal encephalopathy can be broadly divided into perinatal asphyxia [hypoxic–ischemic encephalopathy (HIE)], perinatal stroke, metabolic encephalopathy from inborn errors of metabolism, congenital neonatal central nervous system infections, and severe birth trauma[2]. Perinatal asphyxia, more appropriately known as HIE, is characterized by clinical and laboratory evidence of acute or subacute brain injury due to asphyxia. Birth asphyxia causes 23% of all neonatal deaths worldwide[3]. Hypoxic–ischemic injury is a major cause of death and cerebral palsy in children. In preterm infants, hypoxic–ischemic injury is even more common; it occurs in 5% of infants born before 32 weeks of gestational age[4]. The common pathophysiologic processes that result in hypoxic–ischemic injury are diminished cerebral blood flow (ischemia) and reduced blood oxygenation (hypoxemia)[5]. Neonatal brain injury often not reach the diagnosis, especially in premature infants with very low birth weight, because obvious signs are lacking or because signs that are present are attributed to developmental immaturity[6]. MRI is the most sensitive technique for depicting the developing brain, because it can provide highly detailed images of brain structures without exposing infants to ionizing radiation and its associated health risks[7]. MRI is used with increasing frequency to evaluate the neonatal brain because it can provide important diagnostic and prognostic information that is needed for optimal treatment and appropriate counseling. Special care must be taken in preparing encephalopathic neonates for an MR study, transporting them from the ICU, monitoring their vital signs, and optimizing MR sequences and protocols[7]. The aim of this work is to throw light on the predictive value of MRI as a safe and superior neuroimaging technique in cases of HIE.
Patients and methods | | |
This progressive study was conducted on 30 neonates with HIE referred to the Radiology Department at Menoufia University Hospitals for the assessment of advanced magnetic resonance techniques during the period from July 2019 to December 2020. Ethical consideration: the study received approval of the ethics committee of Faculty of Medicine, Menoufia University. A written informed consent was taken from the parents or caregivers and written informed consent was obtained from them. Study population: 30 neonates with HIE were included in the study. They study group consisted of 17 males and 13 females, with age ranges from 2 to 20 months. All patients were selected according to the inclusion and exclusion criteria: Inclusion criteria: Neonatal HIE as defined by every individual study. Any neonates from the age of 2 to 20 months. Brain MRI performed within the first 4 weeks of life. Outcomes reported for a follow-up of at least 12 months of postnatal age. Exclusion criteria: some neonates who were unfit for the examination especially with a low oxygen saturation of less than 90% due to lack of oxygen source in hands during transportation to the Radiology Department were excluded from the study. Congenital malformations or major dysmorphic features, congenital viral infections and defined metabolic syndromes.
All patients included in the study were subjected to the following: patient's consent was taken for radiological examination, full history taking including personal history and patient's complaints were recorded, history of the present illness, past history including previous investigations or operations is recorded. Perinatal history including prenatal history, natal history, postnatal, family history of similar cases was taken, full clinical examination to detect the level of consciousness, tendon reflex, muscle tone, presence of seizures, time of birth, and causes of admission. MRI evaluation was performed at closed 1.5 T MR system (Toshiba) Tokyo, Japan using a standard imaging head coil. Our examination included the following sequences: conventional MRI sequences including T2WI (axial across the brain), T2WI (axial and coronal across CPA), T1WI axial and coronal across CPA, and axial FLAIR across the whole brain. MR advanced techniques including diffusion-weighted images (DWI, axial across the brain). Reconstruction was done using a sophisticated workstation (General Electric) New York, United States including coronal, sagittal oblique, and MIP reformatting. The parameters of the different sequences were as follows: T2WI (TR 4045 ms, TE110 mm, FOV 23 × 18.5 cm, flip angle 90°, slice thickness 5 mm, and interslice gap 1 mm), thin-cut T2WI (TR 3360 ms, TE 81 mm, FOV 17 × 15 cm, flip angle 90°, slice thickness 3 mm, and interslice gap 1 mm), thin-cut T2WI (TR 500 ms, TE 10 mm, FOV 17 × 15 cm, flip angle 90°, slice thickness 3 mm and interslice gap 0.3 mm), FLAIR (TR 10 000 ms, TE 140 mm, FOV 23 × 23 cm, flip angle 90°, slice thickness 5 mm, and interslice gap 1 mm), DWI (TR 2095 ms, TE140 mm, FOV 23 × 23 cm, flip angle 90°, slice thickness 5 mm, and interslice gap 1 mm). The diffusion sensitizing gradients were applied with a b factor of 0 and 1000 mm2/s per axis in each patient. The b-value used in this study has been determined by the specifications of the MR scanner. Apparent diffusion coefficient (ADC) maps were automatically reconstructed for all DWI and used for the measurement of ADC values in regions of interest at the center of the abnormality area. The ADC values were expressed in × 10−3 mm2/s.
Statistical analysis
Results were tabulated and statistically analyzed using a standard computer program using Microsoft Excel 2017 and SPSS V.25 program (SPSS Inc., Chicago, Illinois, USA). Descriptive statistics included description of data that was in the form of mean ± SD for quantitative data, and frequency and proportion for qualitative data. Analytical statistics included χ2, Mann–Whitney test, Kruskal–Wallis H test. P value less than 0.05 was considered statistically significant.
Results | | |
The age of the participants included in this study at examination ranged from 2 to 20 months with a mean of 8.80 ± 5.48 month. More than half (56.7%) of them were males and 43.3% were females; more than two-third (66.7%) of them were preterm and 33.3% were full term, 66.7% had irritable level of consciousness and 80% had increased tendon reflex, regarding causes of admission and muscle tone, most of the participants (66.7%) had obstructed delivery, 73.3% had seizures, hypertonia was found in 19 (63.3%) participants, followed by hypotonia presented in six (20%) participants, followed by 20% had low placental blood flow, 6.7% had fetal infection, and preeclampsia and flaccid in five (16.7%) participants [Table 1]. Most of the studied participants had changes (83.3%) and 30% had periventricular leukomalacia, 20% had basal ganglia ischemia, and 26.7% had focal encephalomalacia. Also, atrophic changes were found in three (10%) participants, intraventricular hemorrhage was presented in one (3.3%) participant, and restricted DW in six (20%) participants. ADC was in the range 0–3.6 with mean 1.56 ± 1.22 and median 3.60 [Table 2]. Tendon reflex (P = 0.04), muscle tone (P = 0.016), and periventricular leukomalacia (P = 0.047) were significantly related with DW. Also, basal ganglia ischemia was highly significantly related with DW (P < 0.001), while there was no statistical relation between DW with Apgar score at 5 min, MRI findings in relation to DW and seizures (P > 0.05) [Table 3]. The ADC value was significantly increased with hypertonia (1.75 ± 1.21) and hypotonia (1.52 ± 1.51) than flaccid (0.86 ± 0.67) with P = 0.0269. There was no statistically significant relation between ADC value with Apgar score, time of birth at 5 min. Also, there was statistically highly significant relation between ADC value with MRI findings among the studied neonates (P < 0.001). Except periventricular leukomalacia and intraventricular hemorrhage were not significantly related with the ADC value (P > 0.05) [Table 4]. In case 1, full-term, 8 months with a history of obstructed vaginal delivery and low APGAR score less than 7, presented with delayed movement [Figure 1], while in case 2, preterm, 9 months with a history of obstructed vaginal delivery and low APGAR score less than 7 or, presented with seizures, bilateral lower hypotonia, and disturbed feeding [Figure 2]. | Figure 1: (a) Axial T1 WI shows low signal focus lesion at the left basal ganglia-associated ex vacuum dilatation of adjacent left lateral ventricles; (b) high signal intensity on axial T2 WI; and (c) on axial FLAIR surrounded by gliosis; (d) not restricted on DWI; (e) with an ADC value of 3.08×10−3 mm2/s. The findings were matching with left basal ganglia focal encephalomalacia. ADC, apparent diffusion coefficient; WI, weighed imaging.
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| Figure 2: (a) Axial T1 WI shows low signal in bilateral basal ganglia and parietal subcortical (recent ischemia); (b) high signal on axial T2 WI; (c) low signal on axial FLAIR; (d) restricted on DWI with (e) an ADC value of 0.3 × 10−3 mm2/s. The findings were matching with bilateral acute basal ganglia and frontoparietal hypoxic–ischemic injury. ADC, apparent diffusion coefficient; WI, weighed imaging.
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| Table 1: Sociodemographic, clinical data, and clinical presentation of all participants
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| Table 2: MRI findings and apparent diffusion coefficient of all participants
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| Table 3: Clinical presentation and MRI findings in relation to diffusion weighted value
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| Table 4: Apparent diffusion coefficient value in relation to clinical data, clinical presentation, and MRI findings of the studied neonates
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Discussion | | |
Neonatal encephalopathy continues to be an important cause of neonatal mortality and morbidity in the United States. Hypoxic–ischemic injury, which is also known as HIE, refers to the subset of neonatal encephalopathy that result from a hypoxic or ischemic event, often in the setting of perinatal asphyxia, which leads to hypoxemia and hypercapnia[8]. MRI is the most sensitive technique for depicting the developing brain, because it can provide highly detailed images of brain structures without exposing infants to ionizing radiation and associated health risks[9]. The study by Aun et al.[8] found that the population enrolled in their study comprised 36 neonates, 25 (69.4%) males and 11 (30.6%) females. These results come in our range (56.7% males and 43.3% females). Also, the study by Pasquariello[10], included 23 infants (14 males, nine females), with a mean gestational age of 39.99 weeks. In addition, the study by Twomey et al.[11] reported that 26 infants were included in the study. The mean gestational age was 40.1 weeks. Early MRI occurred at a mean age of 5.4 days. Another study by Bersani et al.[12] reported that males are the most but there was no statistical significance between cases and controls as regards gender. On the other side, 73.3% had seizures in the current study. Seo et al.[13] come in the same range who found 78.7% frequency of clinical seizures and a 70% frequency of electrographic seizures among their therapeutic hypothermia treated infants. The abnormal brain MRI group showed significantly more clinical seizures (78.7 vs. 55.8%). Also, several studies by Wusthoff et al.[14] showed that seizures occur frequently with HIE at presentation, during cooling, and with rewarming. Therefore, continuous recording of amplitude electroencephalogram has been shown to be useful beyond the first 6 h of life. The development of the sleep–wake cycle within 36 h of birth in infants with HIE was reported to be associated with good neurodevelopmental outcomes as shown in the study by Thoresen et al.[15]. Overall Dixon et al.[16] revealed the risk of poor outcome on long-term follow-up, which is reported to increase threefold with a history of seizures. Perinatally, the incidence of fetal heart-rate deceleration was significantly more prevalent in the severe MRI group (97 vs. 73%). Also, the study by Shankaran et al.[17] reported that one clinical trial reported that therapeutic hypothermia-treated infants (n = 97) had a 71% incidence of fetal heart-rate deceleration and the severe MRI group had a 97% incidence of fetal heart-rate deceleration. Another study by Groenendaal and de Vries[18] found that routine use of MRI has shown that small subdural hemorrhages are common. In a newborn with relatively mild HIE, these may contribute to seizures. Moreover, de Vries and Groenendaal[19] found a population prevalence of 6.2 in 100 000 live births. All infants presented with encephalopathy and 65% with seizures. In additionally, the study by Chang et al.[20] revealed that the number of clinical seizures was significantly higher in the abnormal MRI group than in the normal MRI group. Another study by Badawi et al.[21] found that growth restriction was the strongest risk factor for neonatal encephalopathy in their study. These are in the same trend of our study (66.7% preterm and 33.3% full term, 66.7% had obstructed delivery, 20% had placenta low blood flow, then 6.7% had fetal infection and preeclampsia). On the other hand, Schump[22] reported that HIE is much more common in full-term infants compared with preterm infants. Li et al.[23] found a positive correlation between MRI and DW-MRI studies with higher efficacy of DW-MRI in the evaluation of HIE. Regarding ADC value, Maher et al.[24] found that an ADC value of 0.8 × 10−3 mm2/s was detected as a cutoff point between severe and mild/moderate cases. They could not detect any significant differences between neonates who were imaged before or after 7 days in our results and no significant correlation between ADC values and the age of neonates at the time of imaging. Another study by Hunt et al.[25] found that mean ADC values (among survivors after perinatal asphyxia) were 0.89 ± 0.17 in PLIC, and it was also associated with poor motor outcome, whereas the mean ADC values (among nonsurvivors) were 0.75 ± 0.17. Rutherford et al.[26] found normal ADC values in moderate WM and BGT lesions during the first week after the hypoxic–ischemic event, and this means that normal ADC values did not exclude hypoxic–ischemic brain damage in neonates. Several studies mentioned above are agree with our results; the ADC value was significantly increased with hypertonia, hypotonia, and flaccid but no relation with sex, time of birth, causes of admission, level of consciousness, tendon reflex, and seizures. Also, Wolf et al.[27] found that DWI and ADC measurements are helpful in improving detection and depiction of the extent of injury in the setting of acute and/or subacute HIE. Another study by Cimpersek et al.[28] found that ADC values measured in the PLIC/T and in the WM were most associated with clinical outcome, but scores given by the morphological MRI scoring system in these areas were not. Instead, they have shown an association between clinical outcome and MRI scores given in the area of BG/T and cortex. Differences may be present due to the fact that the morphological MRI scoring system is fairly subjective and depends on the person evaluating the image. Therefore, ADC values have a greater role and are more objective in the evaluation of lesions of the deep brain areas. Also, a significant relation was found in our results between ADC value with MRI findings, except that periventricular leukomalacia and intraventricular hemorrhage were not associated with ADC value. In this line, Rana et al.[29] found the raised ADC value in chronically affected white and gray matter as well as the appearance of these on conventional MRI, which was significantly associated with morbidity in a cohort of infants with HIE. The raised ADC values in abnormal white matter was significantly associated with motor cerebral palsy. Barkovich et al.[30] also demonstrated a strong relationship between the ADC value and observed changes on conventional MRI, this supports the possibility that the signal abnormalities, mostly deaths occur in the first week of life due to multiple organ failure or redirection of care. Some infants with severe neurologic disabilities die in their infancy from aspiration pneumonia or systemic infections[23].
Conclusion | | |
MRI findings were significantly associated with DW and ADC values. MRI findings indicated that periventricular leukomalacia and basal ganglia ischemia were significantly associated with DW value. Moreover, it was noted that MRI is a very efficient tool in evaluating the morphometry of HIE. Its noninvasiveness and no exposure to ionizing radiation is an added advantage. However, experience and understanding of the principles are essential for an accurate diagnosis. Also, DW and ADC values may add value to routine MRI examination. However, there is limitation in our study as regards the small number of cases, lack of clinical data, and long-term follow-up of cases.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]
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