Original Article
Diagnoses in Pediatric Patients With Magnetic Resonance Imaging (MRI) Lesions Suspicious for Demyelination
Journal of Child Neurology 1-7 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815578522 jcn.sagepub.com
Michael L. Sweeney, MD1, Marcia Kukreja, MD2, Paul S. Horn, PhD1,3, and Shannon M. Standridge, DO, MPH1
Abstract Magnetic resonance imaging (MRI) studies of the brain in pediatric patients frequently show abnormal white matter lesions, which may be concerning for demyelinating disease. This study aimed to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. A retrospective chart review was performed on MRI reports of patients who underwent imaging evaluation at a single tertiary pediatric hospital. Of 299 patients identified, 192 presented with acute neurologic complaints. In this group, 5 discrete lesions, African American race, and having brain stem, thalamic, cerebellar, or optic nerve lesions was associated with the patient being diagnosed with a disease that required further treatment. The other 107 patients underwent MRI for other indications. Among these subjects, having lesions within the corpus callosum or cerebellum was associated with being diagnosed with a disease requiring further treatment. Keywords demyelinating disease, pediatric, MRI Received August 11, 2014. Received revised December 15, 2014. Accepted for publication February 08, 2015.
Magnetic resonance imaging (MRI) is commonly used for research applications and to aid clinicians in the diagnosis of various clinical conditions. MRI of the brain is used to evaluate patients for a wide variety of underlying pathology, including mass lesions, developmental/structural brain abnormalities, inflammatory disease, vascular abnormalities, and white matter diseases. As the resolution and sensitivity of MRI continues to improve, there has been a correlating increase in the identification of abnormalities within the central nervous system. In children, white matter lesions may be a sign of a disease process such as a primary demyelinating disease, metabolic diseases, vascular abnormalities, inflammatory conditions, neoplasms, trauma, or infectious processes.1,2 These lesions may also represent incidental findings of uncertain significance. Certain populations of patients have been described to have higher incidence of white matter lesions, such as those with migraines or epilepsy.3,4 This holds true in the pediatric population as well.3,5-9 Oftentimes, the abnormalities found on MRI are concerning to the neuroradiologist for demyelinating disease. Certain findings are more suggestive of a primary central nervous system demyelinating disease such as multiple sclerosis. In adults, when the lesions are described as ovoid, well-circumscribed, homogenous, and are located in the periventricular white matter or
corpus callosum, demyelinating pathology is suggested.10 Studies exist looking at predictive factors for recurrence of demyelination in children who present with a first-time demyelinating episode.11 However, in children who do not present with acute neurologic deficits or in children with white matter lesions that do not clearly explain their neurologic abnormalities, it is difficult to apply these predictive factors to this patient population. The primary objective of this study was to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. We also sought to estimate
1
Department of Child Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA 2 Department of Radiology, Texas Children’s Hospital, Houston, TX, USA 3 Division of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Corresponding Author: Michael L. Sweeney, MD, Division of Child Neurology, Cincinnati Children’s Hospital Medical Center, 3333 Burnett Ave., Cincinnati, OH 45229, USA. Email: [email protected]
Downloaded from jcn.sagepub.com at UCSF LIBRARY & CKM on April 14, 2015
2
Journal of Child Neurology
which clinical and imaging characteristics increased the odds of requiring medical intervention or imaging follow-up.
Methods Following institutional review board approval, pediatric patients were identified using a search of brain MRI reports from January 1, 2006, until December 31, 2011, at a single pediatric hospital that provides primary care services and is also a major referral center for tertiary care. The search was completed using Softek Illuminate software (Softek Solutions, Inc, Kansas City, KS). In order to identify studies in which lesions identified were suspicious for demyelination, reports were searched for the phrases ‘‘demyelination,’’ ‘‘demyelinating,’’ ‘‘multiple sclerosis,’’ ‘‘acute disseminated encephalomyelitis,’’ ‘‘ADEM,’’ ‘‘optic neuritis,’’ ‘‘neuromyelitis optica,’’ and ‘‘NMO.’’ An additional search of ‘‘white matter lesion’’ yielded no additional unique subjects. Studies were interpreted by 1 of 6 clinical neuroradiologists at that time of the scan. Images were not re-reviewed as part of this study. One neuroradiologist (MK) performed the database search. All MRI studies were performed on a 1.5- or 3-Tesla MRI scanner. All scans included, at minimum, T1-weighted, T2-weighted and fluid-attenuated inversion recovery sequences. Of the studies identified in the search, 64 were excluded because of absence of clinical data. In these instances, the child received no clinical care at our institution aside from the MRI study. A total of 58 additional studies were excluded because of the subject having a prior diagnosis, which explained the imaging findings. All other subjects identified were included. Following the identification of studies, a review of the electronic patient records was performed. Patient data were collected, including demographics, existing diagnoses at time of initial MRI, and laboratory data pertaining to the evaluation of the MRI abnormalities, and entered into a standard data collection form. Data obtained from the initial MRI report included the indication for MRI, the number and location of lesions, and determination of enhancement if gadolinium was administered. Subsequent MRI scans were also evaluated for changes in the appearance and number of lesions. Hospital and clinic encounters from January 1, 2006, to March 1, 2013, were evaluated to determine if a diagnosis pertaining to the MRI lesion was made, when the diagnosis was made, and the diagnostic criteria used. The reviewer of the clinical data was not blinded to the MRI reports. Diagnoses of primary central nervous system demyelinating diseases made by the clinician responsible for the clinical care of the patient were verified by the reviewer using the 2007 International Pediatric Multiple Sclerosis Study Group diagnostic criteria.12 Patients were first classified into 2 groups according to their presenting symptoms and indication for MRI. Subjects placed into group A included those with acute neurologic presentations, including altered mental status, seizure or spell, vision complaints, an abnormal neurologic exam (the abnormal examination findings were to be new to the subject and included in the reason for obtaining an MRI scan), dizziness or vertigo, and urinary retention. Subjects placed into group B included those subjects who received an MRI study to evaluate developmental delay, headaches/migraines, microcephaly or macrocephaly, psychiatric disease (these subjects had chronic psychiatric disease and were separated from the subjects with acute changes in mental status), head trauma, screening as part of an evaluation of a systemic illness, an endocrine abnormality warranting head imaging, and follow-up from a previous head CT or MRI which was abnormal but did not have lesions suspicious for demyelination.
Within each group, subjects were then classified according to the diagnosis assigned, into an ‘‘intervention’’ or ‘‘no intervention’’ group. Diagnoses that led to the patient receiving medical therapy, admission to the hospital, or referral to a specialist were included in the ‘‘intervention’’ group. These diagnoses included multiple sclerosis, acute disseminated encephalomyelitis, optic neuritis, central nervous system infection, neuromyelitis optica, central nervous system vasculitis, posterior reversible encephalopathy syndrome, central nervous system neoplasm, Rasmussen encephalitis, and central pontine myelinolysis. All others were placed in the ‘‘no intervention’’ group. Data were analyzed in order to identify factors linked to the intervention versus nonintervention within each of the groups A and B. Analyses of the following categorical variables with respect to ‘‘intervention’’ versus ‘‘no intervention’’ were assessed using Fisher exact test: sex, race, MRI study indication, and MRI lesion location. Logistic regression was used to examine the effects of key demographic and clinical variables on the response ‘‘intervention’’ or ‘‘no intervention.’’ The following variables were assessed in this model: age (
Diagnoses in Pediatric Patients With Magnetic Resonance Imaging (MRI) Lesions Suspicious for Demyelination
Journal of Child Neurology 1-7 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073815578522 jcn.sagepub.com
Michael L. Sweeney, MD1, Marcia Kukreja, MD2, Paul S. Horn, PhD1,3, and Shannon M. Standridge, DO, MPH1
Abstract Magnetic resonance imaging (MRI) studies of the brain in pediatric patients frequently show abnormal white matter lesions, which may be concerning for demyelinating disease. This study aimed to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. A retrospective chart review was performed on MRI reports of patients who underwent imaging evaluation at a single tertiary pediatric hospital. Of 299 patients identified, 192 presented with acute neurologic complaints. In this group, 5 discrete lesions, African American race, and having brain stem, thalamic, cerebellar, or optic nerve lesions was associated with the patient being diagnosed with a disease that required further treatment. The other 107 patients underwent MRI for other indications. Among these subjects, having lesions within the corpus callosum or cerebellum was associated with being diagnosed with a disease requiring further treatment. Keywords demyelinating disease, pediatric, MRI Received August 11, 2014. Received revised December 15, 2014. Accepted for publication February 08, 2015.
Magnetic resonance imaging (MRI) is commonly used for research applications and to aid clinicians in the diagnosis of various clinical conditions. MRI of the brain is used to evaluate patients for a wide variety of underlying pathology, including mass lesions, developmental/structural brain abnormalities, inflammatory disease, vascular abnormalities, and white matter diseases. As the resolution and sensitivity of MRI continues to improve, there has been a correlating increase in the identification of abnormalities within the central nervous system. In children, white matter lesions may be a sign of a disease process such as a primary demyelinating disease, metabolic diseases, vascular abnormalities, inflammatory conditions, neoplasms, trauma, or infectious processes.1,2 These lesions may also represent incidental findings of uncertain significance. Certain populations of patients have been described to have higher incidence of white matter lesions, such as those with migraines or epilepsy.3,4 This holds true in the pediatric population as well.3,5-9 Oftentimes, the abnormalities found on MRI are concerning to the neuroradiologist for demyelinating disease. Certain findings are more suggestive of a primary central nervous system demyelinating disease such as multiple sclerosis. In adults, when the lesions are described as ovoid, well-circumscribed, homogenous, and are located in the periventricular white matter or
corpus callosum, demyelinating pathology is suggested.10 Studies exist looking at predictive factors for recurrence of demyelination in children who present with a first-time demyelinating episode.11 However, in children who do not present with acute neurologic deficits or in children with white matter lesions that do not clearly explain their neurologic abnormalities, it is difficult to apply these predictive factors to this patient population. The primary objective of this study was to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. We also sought to estimate
1
Department of Child Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA 2 Department of Radiology, Texas Children’s Hospital, Houston, TX, USA 3 Division of Biostatistics & Epidemiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA Corresponding Author: Michael L. Sweeney, MD, Division of Child Neurology, Cincinnati Children’s Hospital Medical Center, 3333 Burnett Ave., Cincinnati, OH 45229, USA. Email: [email protected]
Downloaded from jcn.sagepub.com at UCSF LIBRARY & CKM on April 14, 2015
2
Journal of Child Neurology
which clinical and imaging characteristics increased the odds of requiring medical intervention or imaging follow-up.
Methods Following institutional review board approval, pediatric patients were identified using a search of brain MRI reports from January 1, 2006, until December 31, 2011, at a single pediatric hospital that provides primary care services and is also a major referral center for tertiary care. The search was completed using Softek Illuminate software (Softek Solutions, Inc, Kansas City, KS). In order to identify studies in which lesions identified were suspicious for demyelination, reports were searched for the phrases ‘‘demyelination,’’ ‘‘demyelinating,’’ ‘‘multiple sclerosis,’’ ‘‘acute disseminated encephalomyelitis,’’ ‘‘ADEM,’’ ‘‘optic neuritis,’’ ‘‘neuromyelitis optica,’’ and ‘‘NMO.’’ An additional search of ‘‘white matter lesion’’ yielded no additional unique subjects. Studies were interpreted by 1 of 6 clinical neuroradiologists at that time of the scan. Images were not re-reviewed as part of this study. One neuroradiologist (MK) performed the database search. All MRI studies were performed on a 1.5- or 3-Tesla MRI scanner. All scans included, at minimum, T1-weighted, T2-weighted and fluid-attenuated inversion recovery sequences. Of the studies identified in the search, 64 were excluded because of absence of clinical data. In these instances, the child received no clinical care at our institution aside from the MRI study. A total of 58 additional studies were excluded because of the subject having a prior diagnosis, which explained the imaging findings. All other subjects identified were included. Following the identification of studies, a review of the electronic patient records was performed. Patient data were collected, including demographics, existing diagnoses at time of initial MRI, and laboratory data pertaining to the evaluation of the MRI abnormalities, and entered into a standard data collection form. Data obtained from the initial MRI report included the indication for MRI, the number and location of lesions, and determination of enhancement if gadolinium was administered. Subsequent MRI scans were also evaluated for changes in the appearance and number of lesions. Hospital and clinic encounters from January 1, 2006, to March 1, 2013, were evaluated to determine if a diagnosis pertaining to the MRI lesion was made, when the diagnosis was made, and the diagnostic criteria used. The reviewer of the clinical data was not blinded to the MRI reports. Diagnoses of primary central nervous system demyelinating diseases made by the clinician responsible for the clinical care of the patient were verified by the reviewer using the 2007 International Pediatric Multiple Sclerosis Study Group diagnostic criteria.12 Patients were first classified into 2 groups according to their presenting symptoms and indication for MRI. Subjects placed into group A included those with acute neurologic presentations, including altered mental status, seizure or spell, vision complaints, an abnormal neurologic exam (the abnormal examination findings were to be new to the subject and included in the reason for obtaining an MRI scan), dizziness or vertigo, and urinary retention. Subjects placed into group B included those subjects who received an MRI study to evaluate developmental delay, headaches/migraines, microcephaly or macrocephaly, psychiatric disease (these subjects had chronic psychiatric disease and were separated from the subjects with acute changes in mental status), head trauma, screening as part of an evaluation of a systemic illness, an endocrine abnormality warranting head imaging, and follow-up from a previous head CT or MRI which was abnormal but did not have lesions suspicious for demyelination.
Within each group, subjects were then classified according to the diagnosis assigned, into an ‘‘intervention’’ or ‘‘no intervention’’ group. Diagnoses that led to the patient receiving medical therapy, admission to the hospital, or referral to a specialist were included in the ‘‘intervention’’ group. These diagnoses included multiple sclerosis, acute disseminated encephalomyelitis, optic neuritis, central nervous system infection, neuromyelitis optica, central nervous system vasculitis, posterior reversible encephalopathy syndrome, central nervous system neoplasm, Rasmussen encephalitis, and central pontine myelinolysis. All others were placed in the ‘‘no intervention’’ group. Data were analyzed in order to identify factors linked to the intervention versus nonintervention within each of the groups A and B. Analyses of the following categorical variables with respect to ‘‘intervention’’ versus ‘‘no intervention’’ were assessed using Fisher exact test: sex, race, MRI study indication, and MRI lesion location. Logistic regression was used to examine the effects of key demographic and clinical variables on the response ‘‘intervention’’ or ‘‘no intervention.’’ The following variables were assessed in this model: age (
