Transient Hypermetabolism of the Basal Ganglia Following Perinatal Hypoxia

doi:10.1016/j.pediatrneurol.2007.01.004

Pediatric Neurology

Volume 36, Issue 5, May 2007, Pages 330-333

https://doi.org/10.1016/j.pediatrneurol.2007.01.004 Get rights and content

Positron emission tomography can be used to evaluate brain function following perinatal hypoxia. This case report demonstrates transient hypermetabolism in the basal ganglia detected by glucose metabolism positron emission tomography study in a newborn who suffered hypoxic-ischemic encephalopathy and developed dystonic cerebral palsy later. A scan repeated at 4 years of age showed severe hypometabolism in the lentiform nuclei and thalami. Transient hypermetabolism in the basal ganglia following perinatal hypoxia may be related to excitotoxic damage causing permanent neurological symptoms in the form of dystonic cerebral palsy. Thus, positron emission tomography can help predict this form of cerebral palsy in neonates.

Introduction

Cerebral palsy is a condition encompassing a group of disorders that affect approximately 2 to 3 per 1000 school-age children. Previous research suggests that perinatal asphyxia accounts for between 3 and 13% of cerebral palsy [1]. Clinically, cerebral palsy is a static condition characterized by abnormal movement and posture; although it can be associated with mental retardation, epilepsy, and other neurologic symptoms, these are not essential features. The three main types of movement disorders related to cerebral palsy are spastic, ataxic, and dystonic/athetoid; this last type may be associated neuropathologically with status marmoratus, a severe injury of the basal ganglia due to perinatal hypoxia-ischemia [2].

Computed tomography and magnetic resonance imaging scans in asphyxiated infants are useful to assess the extent of brain damage and predict neurodevelopmental outcome [3], [4], [5]. Positron emission tomography scanning of glucose metabolism may show metabolic abnormalities even before morphological changes develop, and the patterns of hypometabolism can be correlated with the type of cerebral palsy later in life [6], [7]. In the present case, a transient increase of glucose metabolism in the basal ganglia was seen in an infant who later developed athetoid cerebral palsy associated with severe hypometabolism in the basal ganglia and thalamus, as revealed by a repeat glucose metabolism positron emission tomography study.

Section snippets

Case Report

The patient is a female who was born in September 2001 after 41 weeks gestation to a 26-year-old woman; the child was admitted to the Children’s Hospital of Michigan in Detroit because of complications related to perinatal asphyxia. The pregnancy had been apparently uncomplicated. Labor was induced for post dates and decreased fetal movement. Nonreassuring fetal heart tones were noted, and an emergency cesarean section was done under general anesthesia. At surgery, a uterine rupture and

Discussion

This case report presents longitudinal positron emission tomography findings that demonstrate transient increased glucose metabolism in the basal ganglia in the neonatal period following hypoxic-ischemic encephalopathy, a finding that can be an early indicator of subsequent dystonic/athetoid cerebral palsy. Several neuroimaging modalities have been applied to describe early changes that could be correlated with future clinical findings of such a condition. A previous case report demonstrated

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Cited by (32)

Evaluation of PET imaging as a tool for detecting neonatal hypoxic-ischemic encephalopathy in a preclinical animal model
2024, Experimental Neurology
Hypoxic-ischemic encephalopathy due to insufficient oxygen delivery to brain tissue is a leading cause of death or severe morbidity in neonates. The early recognition of the most severely affected individuals remains a clinical challenge. We hypothesized that hypoxic-ischemic injury can be detected using PET radiotracers for hypoxia ([¹⁸F]EF5), glucose metabolism ([¹⁸F]FDG), and inflammation ([¹⁸F]F-DPA).
A preclinical model of neonatal hypoxic-ischemic brain injury was made in 9-d-old rat pups by permanent ligation of the left common carotid artery followed by hypoxia (8% oxygen and 92% nitrogen) for 120 min. In vivo PET imaging was performed immediately after injury induction or at different timepoints up to 21 d later. After imaging, ex vivo brain autoradiography was performed. Brain sections were stained with cresyl violet to evaluate the extent of the brain injury and to correlate it with [¹⁸F]FDG uptake.
PET imaging revealed that all three of the radiotracers tested had significant uptake in the injured brain hemisphere. Ex vivo autoradiography revealed high [¹⁸F]EF5 uptake in the hypoxic hemisphere immediately after the injury (P < 0.0001), decreasing to baseline even 1 d postinjury. [¹⁸F]FDG uptake was highest in the injured hemisphere on the day of injury (P < 0.0001), whereas [¹⁸F]F-DPA uptake was evident after 4 d (P = 0.029), peaking 7 d postinjury (P < 0.0001), and remained significant 21 d after the injury. Targeted evaluation demonstrated that [¹⁸F]FDG uptake measured by in vivo imaging 1 d postinjury correlated positively with the brain volume loss detected 21 d later (r = 0.72, P = 0.028).
Neonatal hypoxic-ischemic brain injury can be detected using PET imaging. Different types of radiotracers illustrate distinct phases of hypoxic brain damage. PET may be a new useful technique, worthy of being explored for clinical use, to predict and evaluate the course of the injury.
Long-term changes in metabolic brain network drive memory impairments in rats following neonatal hypoxia-ischemia
2020, Neurobiology of Learning and Memory
Citation Excerpt :
Interestingly, all HI animals developed cognitive impairments and showed aberrant MBN architecture in the adult phase after neonatal HI insult. It is known that some brain regions are more susceptible to HI damage and are widely reported in the pathophysiology of clinical and experimental HI (Batista, Chugani, Juhász, Behen, & Shankaran, 2007; Biran, Verney, & Ferriero, 2012; Kannan & Chugani, 2010; Liu, Siesjö, & Hu, 2004; Vannucci, Lyons, & Vasta, 1988; Wixey, Reinebrant, & Buller, 2011). It has also been shown that glucose metabolism is significantly lower in severe than in mild and medium hypoxic-ischemic neonates (Shi et al., 2012).
Hypoxia and cerebral ischemia (HI) events are capable of triggering important changes in brain metabolism, including glucose metabolism abnormalities, which may be related to the severity of the insult. Using positron emission microtomography (microPET) with [¹⁸F]fluorodeoxyglucose (¹⁸F-FDG), this study proposes to assess abnormalities of brain glucose metabolism in adult rats previously submitted to the neonatal HI model. We hypothesize that cerebral metabolic outcomes will be associated with cognitive deficits and magnitude of brain injury.
Seven-day-old rats were subjected to an HI model, induced by permanent occlusion of the right common carotid artery and systemic hypoxia. ¹⁸F-FDG-microPET was used to assess regional and whole brain glucose metabolism in rats at 60 postnatal days (PND 60). An interregional cross-correlation matrix was utilized to construct metabolic brain networks (MBN). Rats were also subjected to the Morris Water Maze (MWM) to evaluate spatial memory and their brains were processed for volumetric evaluation.
Brain glucose metabolism changes were observed in adult rats after neonatal HI insult, limited to the right brain hemisphere. However, not all HI animals exhibited significant cerebral hypometabolism. Hippocampal glucose metabolism was used to stratify HI animals into HI hypometabolic (HI-h) and HI non-hypometabolic (HI non-h) groups. The HI-h group had drastic MBN disturbance, cognitive deficit, and brain tissue loss, concomitantly. Conversely, HI non-h rats had normal brain glucose metabolism and brain tissue preserved, but also presented MBN changes and spatial memory impairment. Furthermore, data showed that brain glucose metabolism correlated with cognitive deficits and brain volume outcomes.
Our findings demonstrated that long-term changes in MBN drive memory impairments in adult rats subjected to neonatal hypoxic ischemia, using in vivo imaging microPET-FDG. The MBN analyses identified glucose metabolism abnormalities in HI non-h animals, which were not detected by conventional ¹⁸F-FDG standardized uptake value (SUVr) measurements. These animals exhibited a metabolic brain signature that may explain the cognitive deficit even with no identifiable brain damage.
Changes in brain perfusion in successive arterial spin labeling MRI scans in neonates with hypoxic-ischemic encephalopathy
2019, NeuroImage: Clinical
Citation Excerpt :
The energy failure phase can occur 6 to 15 h after reperfusion and last a few days, leading to delayed cell death (Saliba and Debillon, 2010). The severity of this second phase is related to poor outcome (Batista et al., 2007; Rosenbaum et al., 1997). It still remains unclear whether hyperperfusion contributes to the injury or, on the other hand, represents a compensatory mechanism (Greisen, 2014).
The primary objective of this study was to evaluate changes in cerebral blood flow (CBF) using arterial spin labeling MRI between day 4 of life (DOL4) and day 11 of life (DOL11) in neonates with hypoxic-ischemic encephalopathy (HIE) treated with hypothermia. The secondary objectives were to compare CBF values between the different regions of interest (ROIs) and between infants with ischemic lesions on MRI and infants with normal MRI findings.
We prospectively included all consecutive neonates with HIE admitted to the neonatal intensive care unit of our institution who were eligible for therapeutic hypothermia. Each neonate systematically underwent two MRI examinations as close as possible to day 4 (early MRI) and day 11 (late MRI) of life. A custom processing pipeline of morphological and perfusion imaging data adapted to neonates was developed to perform automated ROI analysis.
Twenty-eight neonates were included in the study between April 2015 and December 2017. There were 16 boys and 12 girls. Statistical analysis was finally performed on 37 MRIs, 17 early MRIs and 20 late MRIs. Eleven neonates had both early and late MRIs of good quality available. Eight out of 17 neonates (47%) had an abnormal on late MRI as performed and 7/20 neonates (35%) had an abnormal late MRI. CBF values in the basal ganglia and thalami (BGT) and temporal lobes were significantly higher on DOL4 than on DOL11. There were no significant differences between DOL4 and DOL11 for the other ROIs. CBF values were significantly higher in the BGT vs. the cortical GM, on both DOL4 and DOL11. On DOL4, the CBF was significantly higher in the cortical GM, the BGT, and the frontal and parietal lobes in subjects with an abnormal MRI compared to those with a normal MRI. On DOL11, CBF values in each ROI were not significantly different between the normal MRI group and the abnormal MRI group, except for the temporal lobes.
This article proposes an innovative processing pipeline for morphological and ASL data suited to neonates that enable automated segmentation to obtain CBF values over ROIs. We evaluate CBF on two successive scans within the first 15 days of life in the same subjects. ASL imaging in asphyxiated neonates seems more relevant when used relatively early, in the first days of life. The correlation of intra-subject changes in cerebral perfusion between early and late MRI with neurodevelopmental outcome warrants investigation in a larger cohort, to determine whether the CBF pattern change can provide prognostic information beyond that provided by visible structural abnormalities on conventional MRI.
Imaging increased glutamate in children with Sturge-Weber syndrome: Association with epilepsy severity
2016, Epilepsy Research
Sturge–Weber syndrome (SWS) is strongly associated with epilepsy. Brain tissue studies have suggested that epileptic activity in SWS is driven by glutamatergic synaptic activity. Here, we used proton magnetic resonance spectroscopic imaging (MRSI) to test if glutamate (GLU) concentrations are increased in the affected hemisphere and if such increases are associated with severity of epilepsy in children with SWS. We also studied the metabolic correlates of MRSI abnormalities, using glucose positron emission tomography (PET) imaging.
3T MRI and glucose PET were performed in 10 children (age: 7–78 months) with unilateral SWS and a history of epilepsy. MRSI data were acquired from the affected (ipsilateral) and non-affected (contralateral) hemispheres. GLU, N-acetyl-aspartate (NAA) and creatine (Cr) were quantified in multiple voxels; GLU/Cr and NAA/Cr ratios were calculated and compared to seizure frequency as well as glucose PET findings.
The highest GLU/Cr ratios were found in the affected hemisphere in all children except one with severe atrophy. The maximum ipsilateral/contralateral GLU/Cr ratios ranged between 1.0 and 2.5 (mean: 1.6). Mean ipsilateral/contralateral GLU/Cr ratios were highest in the youngest children and showed a strong positive correlation with clinical seizure frequency scores assessed at the time of the scan (r = 0.88, p = 0.001) and also at follow-up (up to 1 year, r = 0.80, p = 0.009). GLU increases in the affected hemisphere coincided with areas showing current or previous increases of glucose metabolism on PET in 5 children. NAA/Cr ratios showed no association with clinical seizure frequency.
Increased glutamate concentrations in the affected hemisphere, measured by MRSI, are common in young children with unilateral SWS and are associated with frequent seizures. The findings lend support to the role of excess glutamate in SWS-associated epilepsy.
Localization of Basal Ganglia and Thalamic Damage in Dyskinetic Cerebral Palsy
2016, Pediatric Neurology
Citation Excerpt :
No method currently exists to distinguish between patients with CP likely to benefit from GPi-DBS and those with low likelihood for symptomatic improvement. Imaging and gross pathologic case series have variably suggested that the subthalamic nucleus (STN),11,12 globus pallidus (GP),12,13 putamen,2,12,14-19 thalamus,2,12,13,15-28 lentiform nuclei without differentiation between the putamen and GP,17,19,22-24 and basal ganglia without differentiation between subnuclei20,25-31 are preferentially associated with dyskinetic CP. Summing the conclusions of these individual studies does not provide a consensus on the basal ganglia pathway damage necessary or sufficient to yield dyskinetic CP.
Dyskinetic cerebral palsy affects 15%-20% of patients with cerebral palsy. Basal ganglia injury is associated with dyskinetic cerebral palsy, but the patterns of injury within the basal ganglia predisposing to dyskinetic cerebral palsy are unknown, making treatment difficult. For example, deep brain stimulation of the globus pallidus interna improves dystonia in only 40% of patients with dyskinetic cerebral palsy. Basal ganglia injury heterogeneity may explain this variability.
To investigate this, we conducted a qualitative systematic review of basal ganglia and thalamic damage in dyskinetic cerebral palsy. Reviews and articles primarily addressing genetic or toxic causes of cerebral palsy were excluded yielding 22 studies (304 subjects).
Thirteen studies specified the involved basal ganglia nuclei (subthalamic nucleus, caudate, putamen, globus pallidus, or lentiform nuclei, comprised by the putamen and globus pallidus). Studies investigating the lentiform nuclei (without distinguishing between the putamen and globus pallidus) showed that all subjects (19 of 19) had lentiform nuclei damage. Studies simultaneously but independently investigating the putamen and globus pallidus also showed that all subjects (35 of 35) had lentiform nuclei damage (i.e., putamen or globus pallidus damage); this was followed in frequency by damage to the putamen alone (70 of 101, 69%), the subthalamic nucleus (17 of 25, 68%), the thalamus (88 of 142, 62%), the globus pallidus (7/35, 20%), and the caudate (6 of 47, 13%). Globus pallidus damage was almost always coincident with putaminal damage.
Noting consistent involvement of the lentiform nuclei in dyskinetic cerebral palsy, these results could suggest two groups of patients with dyskinetic cerebral palsy: those with putamen-predominant damage and those with panlenticular damage involving both the putamen and the globus pallidus. Differentiating between these groups could help predict response to therapies such as deep brain stimulation.
Early hyperglycemia is associated with poor gross motor outcome in asphyxiated term newborns
2014, Pediatric Neurology
Citation Excerpt :
Also, in a newborn piglet model with induced hypoxia but without ischemia, administration of dextrose actually prevents brain cell membrane dysfunction.12 The part of the brain most sensitive to asphyxia in the term infant is the basal ganglia.13-15 A buildup of lactic acid in the basal ganglia as shown in magnetic resonance spectroscopy is one of the strongest predictors of poor outcome in term neonatal asphyxia.16-18
Hyperglycemia after ischemic stroke in adults and after near-drowning in children is associated with a poor neurological outcome. Anaerobic metabolism of glucose leads to buildup of lactic acid, free radical production, mitochondrial failure, and ultimately an increase in neurological injury. In asphyxiated infants, high lactate peaks are seen in the basal ganglia with magnetic resonance spectroscopy. Because motor disability in asphyxiated full-term newborns often relates to injury in the basal ganglia, we hypothesized that hyperglycemia and associated buildup of lactic acid may lead to worse gross motor outcome.
Glucose, blood gas values, and demographic data were abstracted from the medical records of 41 term infants with asphyxia and without confounding diagnoses. Their Gross Motor Function Classification System scores were determined from the medical record or by structured telephone interviews.
The outcomes of 14 infants were considered poor on the basis of death within the first 6 months or moderate-to-severe cerebral palsy (Gross Motor Function Classification System score 1-5). The other 27 infants had no gross motor disability (Gross Motor Function Classification System score 0). The highest recorded blood glucose correlated with poor outcome (P = 0.046 by logistic regression). Infants with hyperglycemia (blood glucose > 150 mg/dL) were more likely to have poor outcome (P = 0.017; odds ratio: 5.9; 95% confidence interval: 1.4-24.7).
High blood glucose in the first 12 hours is associated with poor gross motor outcome in this cohort of asphyxiated term infants. Clinicians should avoid hyperglycemia in managing term infants with asphyxia.

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Case reportTransient Hypermetabolism of the Basal Ganglia Following Perinatal Hypoxia

Introduction

Section snippets

Case Report

Discussion

J Pediatr

Brain Dev

Pediatr Neurol

Trends Neurosci

Brain Dev

Brain Res

Intrapartum hypoxic-ischemic cerebral injury and subsequent cerebral palsy: medicolegal issues

Pediatrics

Perinatal asphyxia: MR findings in the first 10 days

AJNR Am J Neuroradiol

Case report
Transient Hypermetabolism of the Basal Ganglia Following Perinatal Hypoxia