- Email: [email protected]
Value of Gadolinium in Brain MRI Examinations for Developmental Delay
Value of Gadolinium in Brain MRI Examinations for Developmental Delay Bradley R. Foerster, MD*, Jamal Ksar, MD*, Myria Petrou, MD*, Petr O. Eldevik, MD*, Pavel V. Maly, MD†, Martha D. Carlson, MD, PhD‡, and Pia C. Sundgren, MD, PhD* The aim of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. A computerized retrospective study identified all brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995–2002 for children under the age of 2 years. Review of the clinical records and magnetic resonance imaging reports identified 170 brain magnetic resonance imaging examinations that were performed for developmental delay. Magnetic resonance imaging studies with enhancing lesions were reviewed by two staff neuroradiologists and two radiology residents. Contrast administration was rated as essential, helpful, or not helpful for each study. In the 107 patients in whom developmental delay was the primary concern, there were no cases in which the findings would have been missed without gadolinium administration. In the 63 patients in whom developmental delay was a secondary concern, there were several cases (11%) where contrast was helpful but not essential in reaching a radiologic diagnosis. In conclusion, intravenous gadolinium has an extremely low yield in children under the age of 2 where developmental delay is the primary concern. In young children for whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly where tumor or infection is clinically suspected. © 2006 by Elsevier Inc. All rights reserved.
Foerster BR, Ksar J, Petrou M, Eldevik PO, Maly PV, Carlson MD, Sundgren PC. Value of gadolinium in brain MRI examinations for developmental delay. Pediatr Neurol 2006;35:126-130.
*Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, †Department of Radiology, University of Lund, Malmo, Sweden, ‡Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan.
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Introduction Developmental delay is relatively common in pediatric patients, affecting 5% to 10% of young children [1–3]. Causes of developmental delay include cerebral dysgenesis, ischemic insult, chromosomal abnormalities, toxic metabolic disorders, genetic syndromes, neurocutaneous disorders, and epileptic syndromes. Early identification of potential causes of developmental delay can be helpful in determining possible interventions and providing prognostic information and genetic counseling for the parents. Over the past years, advancement in imaging techniques has led to the increasing use of imaging studies to determine the cause of these syndromes. Positive findings on neuroimaging can be found in 30% to 60% of patients with mental retardation and developmental delay [4]. Imaging findings can be diagnostic of the child’s condition, such as with cerebral dysgenesis, ischemic insult, or leukodystrophy, and often direct the physician to additional diagnostic testing. Even if the condition identified lacks specific treatment, precise diagnosis is beneficial for the determination of prognosis and family planning. Positive brain imaging findings can localize and confirm the child’s clinical diagnosis. Neuroimaging is recommended as a part of the evaluation of the child with global developmental delay. The presence of neurologic deficits increases the chance of positive brain magnetic resonance imaging findings which is preferred to computed tomography in the evaluation of developmental delay [5]. Intravenous gadolinium contrast is currently administered for nearly all pediatric brain magnetic resonance imaging studies at our institution. A smaller previous study at our institution evaluated the clinical utility of gadolinium and suggested that indiscriminate use of gadolinium contrast material for brain magnetic resonance imaging was not warranted in this age group [6]. To our
Communications should be addressed to: Dr. Sundgren, University of Michigan Health Systems; 1500 E. Medical Center Drive; Ann Arbor, MI 48104. E-mail: [email protected] Received October 21, 2005; accepted February 9, 2006.
© 2006 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2006.02.014 ● 0887-8994/06/$—see front matter
knowledge, clinical guidelines for contrast administration in the imaging of suspected developmental delay have not been clearly delineated. The administration of gadolinium adds both time and cost, not only by the physical administration of the contrast agent and performance of additional imaging sequences but also by the manipulation and analysis of the additional images by the staff (magnetic resonance imaging technicians and clerks) and by the neuroradiologist. The purpose of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. In addition, the radiologic findings were compared with the initial clinical indications that prompted the study. Methods After obtaining Institutional Review Board approval, a computerized retrospective study of radiology information systems was conducted identifying the pediatric brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995 to 2002 for children under the age of 2 years. The patients received gadopentetate dimeglumine (Magnevist, Berlex, Wayne, NJ) at the routine pediatric dose of 0.1 mmol/kg intravenously. All examinations were performed on a 1.5-Tesla Signa MR system (General Electric, Milwaukee, WI). The typical sequences used in these examinations were: sagittal and axial T1 pregadolinium, axial T2, axial fluid-attenuated inversion recovery, axial diffusion-weighted imaging, and axial, coronal, and sagittal T1 postgadolinium. Some of the older examinations were performed using variations of this protocol, but all included pre- and postcontrast imaging. All patients were scanned under conscious sedation or general anesthesia using the standard sedation protocol at our institution. The magnetic resonance imaging reports, clinical indications, and clinical notes were reviewed. Magnetic resonance imaging studies with enhancing lesions were reviewed in a consensus fashion using a junior and senior radiology resident and two staff neuroradiologists. The staff neuroradiologists were provided with the clinical information but were unaware of the content of the radiologic report issued for the study. During the review process, the use of intravenous contrast administration and the value of adding contrast to the examination were evaluated by asking several questions. Did contrast: (1) aid diagnosis? (2) increase lesion conspicuity? (3) help determine the class of pathology? (4) help determine the grade or extent of the tumor? In addition, the reviewers determined if the lesion would have been missed without the administration of gadolinium. Based on the answers to these questions, the examinations were then placed in one of three categories: category I— contrast did not aid diagnosis, category II— contrast did aid diagnosis, and category III— contrast was essential for diagnosis.
Results There were 170 consecutive pediatric brain magnetic resonance imaging examinations using gadolinium in children under the age of 2 years performed at our institution from 1995 to 2002 for the clinical question of developmental delay. The patients were placed in one of two groups on the basis of their initial clinical presentation and indication for the magnetic resonance imaging examination. Patients for whom developmental
Figure 1. Radiologic diagnoses in Group A.
delay was the primary clinical concern were placed into Group A. Patients in whom developmental delay was secondary to other clinical concerns such as seizures or present neurologic deficits were placed into Group B. A total of 107 examinations were performed in patients in whom developmental delay was the primary clinical concern (Group A). Developmental delay was a secondary concern in the remaining 63 examinations (Group B). In Group A, 24 of the patients (22%) were premature, ranging from 24 to 36 weeks gestation. In Group B, 15 of the patients (24%) were premature, ranging from 27 to 36 weeks gestation. Each patient was given a single main radiologic diagnosis. In Group A (developmental delay primary concern), nearly half of the patients (53) had a normal magnetic resonance imaging examination or findings that were normal variants. The next largest category in this patient group was white matter change with 17 patients (16%), followed by diffuse volume loss observed in 14 of the patients (13%). Nine of the patients (8%) had congenital dysgenesis, including: Dandy-Walker variant (4 patients), septo-optic dysplasia (1 patient), Chiari II malformation (1 patient), schizencephaly (1 patient), brachycephaly (1 patient) and polymicrogyria (1 patient). Eight patients had hydrocephalus (7%). Four patients manifested evidence of prior ischemic insult (4%). Two of the patients had nonenhancing tumors, one with the differential diagnosis of lipoma vs dermoid vs cyst vs hamartoma with stable clinical follow-up. The second patient had an intraventricular cyst with stable follow-up magnetic resonance imaging. Sixteen of the premature infants in this group had abnormal magnetic resonance imaging findings, and eight of the premature infants had normal magnetic resonance imaging examinations. Figure 1 summarizes the radiologic diagnoses. In Group B (developmental delay secondary concern), white matter changes were observed in 12 patients (19%). Normal/normal variants and diffuse volume loss were the
Foerster et al: Gadolinium in Brain MRI for Developmental Delay 127
Table 2.
Primary clinical indication in Group B Seizure Neurologic deficit Structural abnormality Metabolic/genetic syndrome
Figure 2. Radiologic diagnoses in Group B.
next largest categories with 11 patients (17%) each. Congenital dysgenesis was present in 9 patients (14%) and included: Chiari I malformation (4 patients), septo-optic dysplasia (2 patients), Dandy-Walker variant (1 patient), developmental venous anomaly (1 patient), and schizencephaly (1 patient). Eight patients (13%) had evidence of prior stroke, and four patients (6%) had hydrocephalus. Three patients (5%) had tumors (medulloblastoma, pilocytic astrocytoma, and choroid plexus papilloma). Three patients (5%) manifested neurocutaneous disorders (tuberous sclerosis with hamartomas (2 patients) and neurofibromatosis Type I). One patient had a chronic bilateral subdural hemorrhage with a history of trauma, and one patient manifested the sequelae of meningitis. Twelve of the premature infants in this group had abnormal magnetic resonance imaging findings, and three of the premature infants had normal magnetic resonance imaging examinations. Figure 2 illustrates the diagnoses for Group B. In Group A (developmental delay primary concern), only three of the studies disclosed pathologic contrast enhancement. These enhancing findings were incidental (parietal scalp venous hemangioma, mastoiditis, and distorted choroid plexus), did not provide an etiology for the child’s condition, and thus were placed in Category I (contrast not helpful). The remaining 104 studies did not have evidence of pathologic enhancement, and the use of contrast was not helpful in making the radiologic diagnosis. Table 1 summarizes the results. Table 1.
Utility of gadolinium in Group A
Radiologic Diagnosis
Category II (Contrast Helpful)
Category III (Contrast Essential)
Normal/normal variant White matter change Diffuse volume loss Congenital dysgenesis Hydrocephalus Stroke Tumor Totals
53 17 14 9 8 4 2 107
— — — — — — — 0
— — — — — — — 0
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In Group B, seizure was the most common indication observed in 49% of this patient subset followed by focal neurologic deficits. Other clinical indications included further evaluation of structural abnormalities documented on ultrasound or computed tomography and suspected or identified metabolic/genetic syndromes. The indications are summarized in Table 2. In Group B, nine of the studies demonstrated pathologic contrast enhancement (Table 3). Contrast enhancement was observed most commonly in patients with neurocutaneous disorders (3 of the 9 patients). With the exception of the developmental venous anomaly (an incidental finding), none of these diagnoses would have been missed without the administration of contrast. Contrast was thought to be helpful (category II) in seven cases especially in the tumor category where it increased the confidence of the readers in excluding additional lesions. As none of the critical radiologic diagnoses would have been missed without the administration of contrast, none of the studies were placed into category III. Table 4 summarizes the results. Discussion To our knowledge, the value of gadolinium in brain magnetic resonance imaging of young children has not been well described in the literature. In particular, clinical guidelines for contrast administration in the imaging of suspected developmental delay have not been clearly delineated. This study provides a strategy for the use of gadolinium in this specific population. The indiscriminate use of gadolinium adds unnecessary costs, scanning time, and interpretation resources and potentially places the patient at added risk for both additional sedation times and the possibility (although extremely low) of contrast reaction. At our institution, gadolinium adds several hundreds of dollars to the cost of the examination. Sedation and anesthesia risks are Table 3.
Category I (Contrast Not Helpful)
31 19 8 5
Enhancing findings in Group B
Patient No. 1 2 3 4 5 6 7 8 9
Finding Tuberous sclerosis with probable hamartoma Tuberous sclerosis with probable hamartoma Neurofibromas Choroid plexus papilloma Right cerebellar medulloblastoma Pineal cyst Leptomeningeal enhancement Leptomeningeal enhancement Developmental venous anomaly
Table 4.
Utility of gadolinium in Group B
Radiologic Diagnosis White matter change Normal/normal variant Diffuse volume loss Congenital dysgenesis Stroke Hydrocephalus Tumor Neurocutanous disorder Subdural hematoma Infection Totals
Category I (Contrast Not Helpful)
Category II (Contrast Helpful)
Category III (Contrast Essential)
12 11 11 9 8 4 0 0
— — — — — — 3 3
— — — — — — — —
1 0 56
— 1 7
— — 0
extremely low, but potential complications in pediatric patients include oxygen desaturation, airway management issues, and oversedation [7]. The 170 patients reviewed in the present study constitute the largest published cohort for magnetic resonance findings in developmental delay in children under the age of 2 years. In Group A, where developmental delay was the primary concern, nearly half of the patients had a normal magnetic resonance imaging examination which is in accord with other published data [8,9]. In comparison to another study which looked at patients with isolated developmental delay, our Group A had a higher percentage of patients with volume loss, lower percentage of patients with cerebral dysgenesis, and a similar percentage of patients with evidence of prior stroke [9]. White matter change was the next most common brain magnetic resonance imaging finding in this population, occurring in approximately 16% of the cases. Further radiologic studies, including more specific magnetic resonance imaging modalities such as magnetic resonance spectroscopy, may be useful in determining the underlying etiologies of these white matter changes. Of note, none of the Group A patients had a malignant neoplasm identified. In Group B (developmental delay secondary concern), the percentage of patients with positive findings (83%) was higher than in the patient subset with isolated developmental delay (Group A), which has been reported previously [8]. In addition, the premature infants in Group B had a higher percentage of abnormal magnetic resonance imaging examinations (80%) compared with the premature infants in Group A (67%). Both of these results are not surprising given that these patients (Group B) had other clinical concerns, such as focal neurologic deficits or seizures. Again, white matter change was a common radiologic finding, occurring in 19% of cases. Ischemic (watershed) white matter injury or metabolic/genetic white matter change (leu-
kodystrophies) are among the suspected pathologic entities included in this category. In Group A, there were no cases in which the findings would have been missed without gadolinium administration, with the most common overriding abnormal radiologic finding being that of structural abnormalities (white matter change, diffuse volume loss, congenital dysgenesis, or hydrocephalus). None of the patients in Group A had a radiologic or eventual clinical diagnosis of infection or malignant neoplasm. In Group B, there were several cases where gadolinium was helpful in making the diagnosis, particularly in patients with tumors or infection. However, the diagnosis would not have been missed in any of the Group B patients given the precontrast imaging findings or the clinical presentation and laboratory tests. Patient selection in this study reflected this institution’s referral bias as a tertiary care neonatal, pediatric neurology, and neurosurgical center. In addition, this is a retrospective study rather than a prospective study and has the inherent bias of looking back in time with the corresponding known clinical diagnosis, rather than making the decision of contrast utility during the initial diagnostic evaluation. Many of the patients did not have imaging or clinical follow-up, particularly the Group A patients with normal magnetic resonance imaging studies. Perhaps with later follow-up imaging, the “normals” would have positive findings, particularly in identifying white matter or other progressive late-onset genetic metabolic or neurocutaneous abnormalities. However, the clinical question is not whether the patient will eventually have identifiable abnormalities in the future, but whether there are current identifiable findings in this young population that can help direct patient care and family counseling. Patient interests and economic considerations require the judicious and appropriate use of limited resources in today’s current medical environment. By using the available clinical information and history, it is appropriate to tailor the requested examination to provide the referring physician and patient’s family with the necessary information. As a result of this study, gadolinium is no longer being routinely administered at our institution for the evaluation of children under the age of 2 years in whom developmental delay is the primary clinical concern. In patients in whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly in patients in whom tumors or infection are suspected.
References [1] Drillen CM, Pickering RD, Drummond MB. Predictive value of screening for different areas of development. Devel Med Child Neurol 1998;30:294-305. [2] Peterson M, Kube D, Palmer F. Classification of developmental delays. Semin Pediatr Neurol 1998;5:2-14.
Foerster et al: Gadolinium in Brain MRI for Developmental Delay 129
[3] Shevell M. The evaluation of the child with a global developmental delay. Semin Pediatr Neurol 1998;5:21– 6. [4] Poussaint TY, Barnes PD. Imaging of the developmentally delayed child. MRI Clinics North Am 2001;9:99-119. [5] Shevell M, Ashwal S, Donley D, et al. Practice parameter: Evaluation of the child with global developmental delay. Am Acad Neurology 2003;60:367– 80. [6] Eldevik P, Brunberg JA. Gadopentetate dimeglumine– enhanced MR of the brain: Clinical utility and safety in patients younger than two years of age. Am J Neuroradiol 1994;15:1001– 8.
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[7] Malviya S, Voepel-Lewis T, Eldevik P, Rockwell T, Wong JH, Tait AR. Sedation and general anaesthesia in children undergoing MRI and CT: Adverse events and outcomes. Br J Anaesthesia 2000;84:743– 8. [8] Van Karnebeek C, Jansweijer M, Leenders A, Offringa M, Hennekam R. Diagnostic investigations in individuals with mental retardation: A systematic literature review of their usefulness. Eur J Hum Genet 2005;13:6-25. [9] Bouhadiba Z, Dacher JN, Monroc M, Vanhulle C, Menard JF, Kalifa G. MRI of the brain in the evaluation of children with developmental delay. J Radiol 2000;81:870 –3.
Foerster BR, Ksar J, Petrou M, Eldevik PO, Maly PV, Carlson MD, Sundgren PC. Value of gadolinium in brain MRI examinations for developmental delay. Pediatr Neurol 2006;35:126-130.
*Department of Radiology, University of Michigan Medical Center, Ann Arbor, Michigan, †Department of Radiology, University of Lund, Malmo, Sweden, ‡Department of Pediatrics, University of Michigan Medical Center, Ann Arbor, Michigan.
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Introduction Developmental delay is relatively common in pediatric patients, affecting 5% to 10% of young children [1–3]. Causes of developmental delay include cerebral dysgenesis, ischemic insult, chromosomal abnormalities, toxic metabolic disorders, genetic syndromes, neurocutaneous disorders, and epileptic syndromes. Early identification of potential causes of developmental delay can be helpful in determining possible interventions and providing prognostic information and genetic counseling for the parents. Over the past years, advancement in imaging techniques has led to the increasing use of imaging studies to determine the cause of these syndromes. Positive findings on neuroimaging can be found in 30% to 60% of patients with mental retardation and developmental delay [4]. Imaging findings can be diagnostic of the child’s condition, such as with cerebral dysgenesis, ischemic insult, or leukodystrophy, and often direct the physician to additional diagnostic testing. Even if the condition identified lacks specific treatment, precise diagnosis is beneficial for the determination of prognosis and family planning. Positive brain imaging findings can localize and confirm the child’s clinical diagnosis. Neuroimaging is recommended as a part of the evaluation of the child with global developmental delay. The presence of neurologic deficits increases the chance of positive brain magnetic resonance imaging findings which is preferred to computed tomography in the evaluation of developmental delay [5]. Intravenous gadolinium contrast is currently administered for nearly all pediatric brain magnetic resonance imaging studies at our institution. A smaller previous study at our institution evaluated the clinical utility of gadolinium and suggested that indiscriminate use of gadolinium contrast material for brain magnetic resonance imaging was not warranted in this age group [6]. To our
Communications should be addressed to: Dr. Sundgren, University of Michigan Health Systems; 1500 E. Medical Center Drive; Ann Arbor, MI 48104. E-mail: [email protected] Received October 21, 2005; accepted February 9, 2006.
© 2006 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2006.02.014 ● 0887-8994/06/$—see front matter
knowledge, clinical guidelines for contrast administration in the imaging of suspected developmental delay have not been clearly delineated. The administration of gadolinium adds both time and cost, not only by the physical administration of the contrast agent and performance of additional imaging sequences but also by the manipulation and analysis of the additional images by the staff (magnetic resonance imaging technicians and clerks) and by the neuroradiologist. The purpose of this study was to evaluate the added utility of gadolinium administration in the magnetic resonance imaging evaluation of developmental delay in children less than 2 years of age. In addition, the radiologic findings were compared with the initial clinical indications that prompted the study. Methods After obtaining Institutional Review Board approval, a computerized retrospective study of radiology information systems was conducted identifying the pediatric brain magnetic resonance imaging examinations using gadolinium performed at our institution from 1995 to 2002 for children under the age of 2 years. The patients received gadopentetate dimeglumine (Magnevist, Berlex, Wayne, NJ) at the routine pediatric dose of 0.1 mmol/kg intravenously. All examinations were performed on a 1.5-Tesla Signa MR system (General Electric, Milwaukee, WI). The typical sequences used in these examinations were: sagittal and axial T1 pregadolinium, axial T2, axial fluid-attenuated inversion recovery, axial diffusion-weighted imaging, and axial, coronal, and sagittal T1 postgadolinium. Some of the older examinations were performed using variations of this protocol, but all included pre- and postcontrast imaging. All patients were scanned under conscious sedation or general anesthesia using the standard sedation protocol at our institution. The magnetic resonance imaging reports, clinical indications, and clinical notes were reviewed. Magnetic resonance imaging studies with enhancing lesions were reviewed in a consensus fashion using a junior and senior radiology resident and two staff neuroradiologists. The staff neuroradiologists were provided with the clinical information but were unaware of the content of the radiologic report issued for the study. During the review process, the use of intravenous contrast administration and the value of adding contrast to the examination were evaluated by asking several questions. Did contrast: (1) aid diagnosis? (2) increase lesion conspicuity? (3) help determine the class of pathology? (4) help determine the grade or extent of the tumor? In addition, the reviewers determined if the lesion would have been missed without the administration of gadolinium. Based on the answers to these questions, the examinations were then placed in one of three categories: category I— contrast did not aid diagnosis, category II— contrast did aid diagnosis, and category III— contrast was essential for diagnosis.
Results There were 170 consecutive pediatric brain magnetic resonance imaging examinations using gadolinium in children under the age of 2 years performed at our institution from 1995 to 2002 for the clinical question of developmental delay. The patients were placed in one of two groups on the basis of their initial clinical presentation and indication for the magnetic resonance imaging examination. Patients for whom developmental
Figure 1. Radiologic diagnoses in Group A.
delay was the primary clinical concern were placed into Group A. Patients in whom developmental delay was secondary to other clinical concerns such as seizures or present neurologic deficits were placed into Group B. A total of 107 examinations were performed in patients in whom developmental delay was the primary clinical concern (Group A). Developmental delay was a secondary concern in the remaining 63 examinations (Group B). In Group A, 24 of the patients (22%) were premature, ranging from 24 to 36 weeks gestation. In Group B, 15 of the patients (24%) were premature, ranging from 27 to 36 weeks gestation. Each patient was given a single main radiologic diagnosis. In Group A (developmental delay primary concern), nearly half of the patients (53) had a normal magnetic resonance imaging examination or findings that were normal variants. The next largest category in this patient group was white matter change with 17 patients (16%), followed by diffuse volume loss observed in 14 of the patients (13%). Nine of the patients (8%) had congenital dysgenesis, including: Dandy-Walker variant (4 patients), septo-optic dysplasia (1 patient), Chiari II malformation (1 patient), schizencephaly (1 patient), brachycephaly (1 patient) and polymicrogyria (1 patient). Eight patients had hydrocephalus (7%). Four patients manifested evidence of prior ischemic insult (4%). Two of the patients had nonenhancing tumors, one with the differential diagnosis of lipoma vs dermoid vs cyst vs hamartoma with stable clinical follow-up. The second patient had an intraventricular cyst with stable follow-up magnetic resonance imaging. Sixteen of the premature infants in this group had abnormal magnetic resonance imaging findings, and eight of the premature infants had normal magnetic resonance imaging examinations. Figure 1 summarizes the radiologic diagnoses. In Group B (developmental delay secondary concern), white matter changes were observed in 12 patients (19%). Normal/normal variants and diffuse volume loss were the
Foerster et al: Gadolinium in Brain MRI for Developmental Delay 127
Table 2.
Primary clinical indication in Group B Seizure Neurologic deficit Structural abnormality Metabolic/genetic syndrome
Figure 2. Radiologic diagnoses in Group B.
next largest categories with 11 patients (17%) each. Congenital dysgenesis was present in 9 patients (14%) and included: Chiari I malformation (4 patients), septo-optic dysplasia (2 patients), Dandy-Walker variant (1 patient), developmental venous anomaly (1 patient), and schizencephaly (1 patient). Eight patients (13%) had evidence of prior stroke, and four patients (6%) had hydrocephalus. Three patients (5%) had tumors (medulloblastoma, pilocytic astrocytoma, and choroid plexus papilloma). Three patients (5%) manifested neurocutaneous disorders (tuberous sclerosis with hamartomas (2 patients) and neurofibromatosis Type I). One patient had a chronic bilateral subdural hemorrhage with a history of trauma, and one patient manifested the sequelae of meningitis. Twelve of the premature infants in this group had abnormal magnetic resonance imaging findings, and three of the premature infants had normal magnetic resonance imaging examinations. Figure 2 illustrates the diagnoses for Group B. In Group A (developmental delay primary concern), only three of the studies disclosed pathologic contrast enhancement. These enhancing findings were incidental (parietal scalp venous hemangioma, mastoiditis, and distorted choroid plexus), did not provide an etiology for the child’s condition, and thus were placed in Category I (contrast not helpful). The remaining 104 studies did not have evidence of pathologic enhancement, and the use of contrast was not helpful in making the radiologic diagnosis. Table 1 summarizes the results. Table 1.
Utility of gadolinium in Group A
Radiologic Diagnosis
Category II (Contrast Helpful)
Category III (Contrast Essential)
Normal/normal variant White matter change Diffuse volume loss Congenital dysgenesis Hydrocephalus Stroke Tumor Totals
53 17 14 9 8 4 2 107
— — — — — — — 0
— — — — — — — 0
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patients patients patients patients
In Group B, seizure was the most common indication observed in 49% of this patient subset followed by focal neurologic deficits. Other clinical indications included further evaluation of structural abnormalities documented on ultrasound or computed tomography and suspected or identified metabolic/genetic syndromes. The indications are summarized in Table 2. In Group B, nine of the studies demonstrated pathologic contrast enhancement (Table 3). Contrast enhancement was observed most commonly in patients with neurocutaneous disorders (3 of the 9 patients). With the exception of the developmental venous anomaly (an incidental finding), none of these diagnoses would have been missed without the administration of contrast. Contrast was thought to be helpful (category II) in seven cases especially in the tumor category where it increased the confidence of the readers in excluding additional lesions. As none of the critical radiologic diagnoses would have been missed without the administration of contrast, none of the studies were placed into category III. Table 4 summarizes the results. Discussion To our knowledge, the value of gadolinium in brain magnetic resonance imaging of young children has not been well described in the literature. In particular, clinical guidelines for contrast administration in the imaging of suspected developmental delay have not been clearly delineated. This study provides a strategy for the use of gadolinium in this specific population. The indiscriminate use of gadolinium adds unnecessary costs, scanning time, and interpretation resources and potentially places the patient at added risk for both additional sedation times and the possibility (although extremely low) of contrast reaction. At our institution, gadolinium adds several hundreds of dollars to the cost of the examination. Sedation and anesthesia risks are Table 3.
Category I (Contrast Not Helpful)
31 19 8 5
Enhancing findings in Group B
Patient No. 1 2 3 4 5 6 7 8 9
Finding Tuberous sclerosis with probable hamartoma Tuberous sclerosis with probable hamartoma Neurofibromas Choroid plexus papilloma Right cerebellar medulloblastoma Pineal cyst Leptomeningeal enhancement Leptomeningeal enhancement Developmental venous anomaly
Table 4.
Utility of gadolinium in Group B
Radiologic Diagnosis White matter change Normal/normal variant Diffuse volume loss Congenital dysgenesis Stroke Hydrocephalus Tumor Neurocutanous disorder Subdural hematoma Infection Totals
Category I (Contrast Not Helpful)
Category II (Contrast Helpful)
Category III (Contrast Essential)
12 11 11 9 8 4 0 0
— — — — — — 3 3
— — — — — — — —
1 0 56
— 1 7
— — 0
extremely low, but potential complications in pediatric patients include oxygen desaturation, airway management issues, and oversedation [7]. The 170 patients reviewed in the present study constitute the largest published cohort for magnetic resonance findings in developmental delay in children under the age of 2 years. In Group A, where developmental delay was the primary concern, nearly half of the patients had a normal magnetic resonance imaging examination which is in accord with other published data [8,9]. In comparison to another study which looked at patients with isolated developmental delay, our Group A had a higher percentage of patients with volume loss, lower percentage of patients with cerebral dysgenesis, and a similar percentage of patients with evidence of prior stroke [9]. White matter change was the next most common brain magnetic resonance imaging finding in this population, occurring in approximately 16% of the cases. Further radiologic studies, including more specific magnetic resonance imaging modalities such as magnetic resonance spectroscopy, may be useful in determining the underlying etiologies of these white matter changes. Of note, none of the Group A patients had a malignant neoplasm identified. In Group B (developmental delay secondary concern), the percentage of patients with positive findings (83%) was higher than in the patient subset with isolated developmental delay (Group A), which has been reported previously [8]. In addition, the premature infants in Group B had a higher percentage of abnormal magnetic resonance imaging examinations (80%) compared with the premature infants in Group A (67%). Both of these results are not surprising given that these patients (Group B) had other clinical concerns, such as focal neurologic deficits or seizures. Again, white matter change was a common radiologic finding, occurring in 19% of cases. Ischemic (watershed) white matter injury or metabolic/genetic white matter change (leu-
kodystrophies) are among the suspected pathologic entities included in this category. In Group A, there were no cases in which the findings would have been missed without gadolinium administration, with the most common overriding abnormal radiologic finding being that of structural abnormalities (white matter change, diffuse volume loss, congenital dysgenesis, or hydrocephalus). None of the patients in Group A had a radiologic or eventual clinical diagnosis of infection or malignant neoplasm. In Group B, there were several cases where gadolinium was helpful in making the diagnosis, particularly in patients with tumors or infection. However, the diagnosis would not have been missed in any of the Group B patients given the precontrast imaging findings or the clinical presentation and laboratory tests. Patient selection in this study reflected this institution’s referral bias as a tertiary care neonatal, pediatric neurology, and neurosurgical center. In addition, this is a retrospective study rather than a prospective study and has the inherent bias of looking back in time with the corresponding known clinical diagnosis, rather than making the decision of contrast utility during the initial diagnostic evaluation. Many of the patients did not have imaging or clinical follow-up, particularly the Group A patients with normal magnetic resonance imaging studies. Perhaps with later follow-up imaging, the “normals” would have positive findings, particularly in identifying white matter or other progressive late-onset genetic metabolic or neurocutaneous abnormalities. However, the clinical question is not whether the patient will eventually have identifiable abnormalities in the future, but whether there are current identifiable findings in this young population that can help direct patient care and family counseling. Patient interests and economic considerations require the judicious and appropriate use of limited resources in today’s current medical environment. By using the available clinical information and history, it is appropriate to tailor the requested examination to provide the referring physician and patient’s family with the necessary information. As a result of this study, gadolinium is no longer being routinely administered at our institution for the evaluation of children under the age of 2 years in whom developmental delay is the primary clinical concern. In patients in whom developmental delay is a secondary concern, we advocate the use of gadolinium particularly in patients in whom tumors or infection are suspected.
References [1] Drillen CM, Pickering RD, Drummond MB. Predictive value of screening for different areas of development. Devel Med Child Neurol 1998;30:294-305. [2] Peterson M, Kube D, Palmer F. Classification of developmental delays. Semin Pediatr Neurol 1998;5:2-14.
Foerster et al: Gadolinium in Brain MRI for Developmental Delay 129
[3] Shevell M. The evaluation of the child with a global developmental delay. Semin Pediatr Neurol 1998;5:21– 6. [4] Poussaint TY, Barnes PD. Imaging of the developmentally delayed child. MRI Clinics North Am 2001;9:99-119. [5] Shevell M, Ashwal S, Donley D, et al. Practice parameter: Evaluation of the child with global developmental delay. Am Acad Neurology 2003;60:367– 80. [6] Eldevik P, Brunberg JA. Gadopentetate dimeglumine– enhanced MR of the brain: Clinical utility and safety in patients younger than two years of age. Am J Neuroradiol 1994;15:1001– 8.
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PEDIATRIC NEUROLOGY
Vol. 35 No. 2
[7] Malviya S, Voepel-Lewis T, Eldevik P, Rockwell T, Wong JH, Tait AR. Sedation and general anaesthesia in children undergoing MRI and CT: Adverse events and outcomes. Br J Anaesthesia 2000;84:743– 8. [8] Van Karnebeek C, Jansweijer M, Leenders A, Offringa M, Hennekam R. Diagnostic investigations in individuals with mental retardation: A systematic literature review of their usefulness. Eur J Hum Genet 2005;13:6-25. [9] Bouhadiba Z, Dacher JN, Monroc M, Vanhulle C, Menard JF, Kalifa G. MRI of the brain in the evaluation of children with developmental delay. J Radiol 2000;81:870 –3.