Christine Saint-Martin

Measurement of brain perfusion in newborns: Pulsed arterial spin labeling (PASL) versus pseudo-continuous arterial spin labeling (pCASL)

Background Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns. Objective To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns. Design/methods We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas. Results A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p < 0.0001). Strong correlation was found between the CBF measured by PASL and pCASL (r = 0.61, p < 0.0001). Conclusion This study demonstrates that both ASL methods are feasible to assess brain perfusion in healthy and sick newborns. However, pCASL might be a better choice over PASL in newborns, as pCASL perfusion maps had a superior image quality that allowed a more detailed identification of the different brain structures.

MRI obtained during versus after hypothermia in asphyxiated newborns

Objective To assess whether the brain MRI results obtained during hypothermia identify the later brain injury observed in asphyxiated newborns after therapy is completed. Patients and methods Asphyxiated newborns treated with hypothermia were prospectively enrolled in this study if they had at least one MRI performed during hypothermia treatment and then another MRI performed around day 10 of life. Results A total of 129 MRI scans were obtained from 43 asphyxiated newborns treated with hypothermia. Sixty per cent developed brain injury; all the brain injuries observed on the late scans were already present on day 2–3 of life during hypothermia, and the extent of injury was similar between the early and late scans. The brain MRI on day 2–3 of life had a sensitivity of 100% (95% CI 84% to 100%) and a specificity of 100% (95% CI 77% to 100%) to identify the presence and extent of later brain injury. Conclusions The brain MRIs performed during hypothermia already permit an accurate definition of the presence and extent of brain injury that later develop in asphyxiated newborns despite treatment. These results may have research and clinical implications for the care of these newborns.

Filamin A Mutation May Be Associated With Diffuse Lung Disease Mimicking Bronchopulmonary Dysplasia in Premature Newborns

Bronchopulmonary dysplasia (BPD) is a common long-term complication in premature newborns requiring ventilatory support and is the most common cause of chronic diffuse lung disease in this population. We present the clinical course of a premature newborn with a complicated neonatal respiratory course that was initially thought to be related to BPD, but it did not respond to the typical therapies for this condition. Due to the findings of periventricular nodular heterotopia, the diagnosis of a filamin A gene mutation was eventually made, which explained the respiratory pathology of this patient. When time of onset and clinical course do not correlate with typical BPD, one should consider alternative diagnoses in premature infants, including neonatal diffuse lung disease.

Newborns Referred for Therapeutic Hypothermia: Association between Initial Degree of Encephalopathy and Severity of Brain Injury (What About the Newborns with Mild Encephalopathy on Admission?).

OBJECTIVE The aim of this article was to describe the severity of brain injury and/or mortality in a cohort of newborns referred for therapeutic hypothermia, in relation to the degree of encephalopathy on admission, and to especially look at the ones with initial mild encephalopathy. STUDY DESIGN Term newborns with perinatal depression referred to our neonatal intensive care unit for possible hypothermia treatment from 2008 to 2012 were enrolled prospectively. The modified Sarnat score on admission was correlated with severity of brain injury on brain imaging and/or autopsy. RESULTS A total of 215 newborns were referred for possible cooling. Sixty percent (128/215) were cooled. Most of the not-cooled newborns with an available brain magnetic resonance imaging (85% = 50/59) had an initial mild encephalopathy, and 40% (20/50) developed brain injury. Some cooled newborns had an initial mild encephalopathy (12% = 13/108); only 31% (4/13) developed brain injury. CONCLUSION Our results demonstrated that several newborns with an initial mild encephalopathy developed subsequent brain injury, especially when they were not cooled.

Does Near-Infrared Spectroscopy Identify Asphyxiated Newborns at Risk of Developing Brain Injury During Hypothermia Treatment?

OBJECTIVE The aim of this article is to assess whether near-infrared spectroscopy (NIRS) identifies, during hypothermia treatment, the asphyxiated newborns who later develop brain injury. STUDY DESIGN In this study, asphyxiated newborns, for whom later brain injury was defined by brain imaging and/or autopsy results, were monitored by NIRS during therapeutic hypothermia. We compared regional cerebral oxygenation saturation (rSO2) measured by NIRS at key time points for newborns who developed or did not develop later brain injury. RESULTS A total of 18 asphyxiated newborns treated with hypothermia were enrolled. rSO2 was higher in the asphyxiated newborns who developed later brain injury. Sensitivity within the first 10 hours of hypothermia treatment for an adverse outcome was 100% (95% confidence interval [CI], 70-100%) and specificity was 83% (95% CI, 36-99%). CONCLUSIONS NIRS appears to identify asphyxiated newborns at risk of developing brain injury as early as the first 10 hours of hypothermia treatment. Thus, NIRS may have an important role as an early outcome predictor in this population.

Injury to the Cerebellum in Term Asphyxiated Newborns Treated with Hypothermia

BACKGROUND AND PURPOSE: Until now, most studies of brain injury related to term neonatal encephalopathy have focused on the cerebrum and ignored the cerebellum. We sought to evaluate whether cerebellar injury occurs in term asphyxiated neonates. MATERIALS AND METHODS: Asphyxiated neonates treated with hypothermia were enrolled prospectively. Severity of brain injury in the cerebrum was scored on each MR imaging obtained during the first month of life; cerebellar injury was recorded when mentioned in the imaging or autopsy report. In addition, for some of the neonates, the ADC and fractional anisotropy were measured in 4 regions of interest in the cerebellum. RESULTS: One hundred seventy-two asphyxiated neonates met the criteria for hypothermia. Cerebellar injury was visible only on conventional imaging of 4% of the neonates for whom brain imaging was available, but it was reported in the autopsy report of 72% of the neonates who died. In addition, 41 of the asphyxiated neonates had a total of 84 ADC and fractional anisotropy maps. Neonates with brain injury described only in the cerebrum demonstrated ADC and fractional anisotropy changes similar to those of the neonates with brain injury in the cerebrum and cerebellum—increased ADC around day 10 of life and decreased fractional anisotropy on day 2–3 of life, around day 10 of life, and around 1 month of age. CONCLUSIONS: The cerebellum may be injured in term neonates after birth asphyxia. These cerebellar injuries are only rarely visible on conventional imaging, but advanced neuroimaging techniques may help to identify them.

Salivary glands of healthy children versus sialorrhea children, is there an anatomical difference? An ultrasonographic biometry

OBJECTIVES There is no literature about the average size of the salivary glands in the pediatric population with drooling (sialorrhea). Studies have shown that some pathologies affect the functionality of the salivary glands. We assessed via ultrasonography the sizes of the submandibular and parotid glands in 9 healthy children who were not suffering from local or systemic diseases that could affect the salivary glands. We also compared this group with a group of 9 patients with sialorrhea. METHODS Volunteers were matched based on age, gender, and BMI. Body weight did not differ more than 20% from ideal weight. The parotid and submandibular glands of 9 patients with sialorrhea without any previous treatment were measured via ultrasound and matched to a healthy control. Children with various causes for drooling were included (neurological disorders, neuromuscular disorders, lack of oral motor control). RESULTS Dimensions of the parotid glands in drooling and healthy patients were: surface area 2.96 cm(2) (SD ±0.90) and 2.81 cm(2) (SD ±0.54); in depth 1.68 cm (SD ±0.24) and 1.61 cm (SD ±0.27); in the axis longitudinal to the horizontal mandibular ramus 3.18 cm (±0.46) and 3.15 cm (SD ±0.45) in drooling and healthy groups respectively. The means of submandibular glands of drooling and healthy patients measured in surface area: 3.20 cm(2) (SD ±0.66) and 3.08 cm(2) (SD ±0.65); anterior-posterior length 1.55 cm (SD ±0.23) and 1.46 cm (SD ±0.23), medio-lateral length 3.07 cm (SD ±0.39) and 3.07 cm (SD ±0.32). There was no statistical significance in comparison with the healthy group control. CONCLUSION The parotid and submandibular salivary glands in the pediatric population do not differ in size in children with or without drooling. Measuring the glands at baseline and post treatment with botulinum toxin injections allows one to evaluate if there are changes in the gland related to the treatment.

Prediction of outcome in asphyxiated newborns treated with hypothermia: Is a MRI scoring system described before the cooling era still useful?

AIM To determine whether an MRI scoring system, which was validated in the pre-cooling era, can still predict the neurodevelopmental outcome of asphyxiated newborns treated with hypothermia at 2 years of age. PATIENTS AND METHOD We conducted a retrospective cohort study of asphyxiated newborns treated with hypothermia. An MRI scoring system, which was validated in the pre-cooling era, was used to grade the severity of brain injury on the neonatal brain MRI. Their neurodevelopment was assessed around 2 years of age; adverse outcome included cerebral palsy, global developmental delay, and/or epilepsy. RESULTS One hundred and sixty-nine newborns were included. Among the 131 newborns who survived and had a brain MRI during the neonatal period, 92% were evaluated around 2 years of age or later. Of these newborns, 37% displayed brain injury, and 23% developed an adverse outcome. Asphyxiated newborns treated with hypothermia who had an adverse outcome had a significantly higher MRI score (p <0.001) compared to those without an adverse outcome. CONCLUSION An MRI scoring system that was validated before the cooling era is still able to reliably differentiate which of the asphyxiated newborns treated with hypothermia were more prone to develop an adverse outcome around 2 years of age.

Brain Temperature Is Increased During the First Days of Life in Asphyxiated Newborns: Developing Brain Injury Despite Hypothermia Treatment

BACKGROUND AND PURPOSE: Therapeutic hypothermia is the current treatment for neonates with hypoxic-ischemic encephalopathy. It is believed to work by decreasing the brain temperature and reducing the baseline metabolism and energy demand of the brain. This study aimed to noninvasively assess brain temperature during the first month of life in neonates with hypoxic-ischemic encephalopathy treated with hypothermia. MATERIALS AND METHODS: Neonates with hypoxic-ischemic encephalopathy treated with hypothermia and healthy neonates were enrolled prospectively. MR imaging was used to identify the presence and extent of brain injury. MR imaging multivoxel spectroscopy was used to derive brain temperatures in the basal ganglia and white matter at different time points during the first month of life. Brain temperature measurements were compared between neonates with hypoxic-ischemic encephalopathy and healthy neonates. RESULTS: Forty-three term neonates with hypoxic-ischemic encephalopathy treated with hypothermia had a total of 74 spectroscopy scans, and 3 healthy term neonates had a total of 9 spectroscopy scans during the first month of life. Brain temperatures were lower in neonates with hypoxic-ischemic encephalopathy during hypothermia, compared with the healthy neonates (respectively, on day 1 of life: basal ganglia, 38.81°C ± 2.08°C, and white matter, 39.11°C ± 1.99°C; and on days 2–3 of life: basal ganglia, 38.25°C ± 0.91°C, and white matter, 38.54°C ± 2.79°C). However, neonates with hypoxic-ischemic encephalopathy who developed brain injury had higher brain temperatures during hypothermia (respectively, on day 1 of life: basal ganglia, 35.55°C ± 1.31°C, and white matter, 37.35°C ± 2.55°C; and on days 2–3 of life: basal ganglia, 35.20°C ± 1.15°C, and white matter, 35.44°C ± 1.90°C) compared with neonates who did not develop brain injury (respectively, on day 1 of life: basal ganglia, 34.46°C ± 1.09°C, and white matter, 33.97°C ± 1.42°C; and on days 2–3 of life: basal ganglia, 33.90°C ± 1.34°C, and white matter, 33.07°C ± 1.71°C). Also, brain temperatures tended to remain slightly higher in the neonates who developed brain injury around day 10 of life and around 1 month of age. CONCLUSIONS: Therapeutic hypothermia using current guidelines decreased the brain temperature of neonates with hypoxic-ischemic encephalopathy during the first days of life but did not prevent an early increase of brain temperature in neonates with hypoxic-ischemic encephalopathy who developed brain injury despite this treatment.

Effect of recurrent onabotulinum toxin A injection into the salivary glands: An ultrasound measurement.

Onabotulinum toxin A (OBTXA) injection is a well‐established therapeutic option for the management of drooling. Many of the children treated undertake repeated injections every 3 to 6 months. We aimed to assess quantitative salivary gland changes via ultrasound imaging after intraglandular injection of OBTXA for sialorrhea treatment in children, as a method that suggests permanent changes in glandular size can cause a decrease in functionality or atrophy.