Neurological and magnetic resonance imaging findings in children with developmental language impairment

Neurologic and radiologic findings in children with well-defined developmental language impairment have rarely been systematically assessed. Children aged 7 to 13 years with developmental language impairment or normal language (controls) underwent language, nonverbal cognitive, motor and neurological assessments, standardized assessment for subtle neurological signs, and magnetic resonance imaging. Nine children with developmental language impairment and 12 controls participated. No focal abnormalities were identified on standard neurological examination. Age and developmental language impairment were independent predictors of neurological subtle signs scores (r(2) = 0.52). Imaging abnormalities were identified in two boys with developmental language impairment and no controls (P = .17). Lesions identified were predicted neither by history nor by neurological examination. Previously unsuspected lesions were identified in almost 25% of children with developmental language impairment. Constraints regarding cooperation and sedation requirements may limit the clinical application of imaging modalities in this population.     

Negative functional coupling between the right fronto-parietal and limbic resting state networks predicts increased self-control and later substance use onset in adolescence

Recent developmental brain imaging studies have demonstrated that negatively coupled prefrontal-limbic circuitry implicates the maturation of brain development in adolescents. Using resting-state functional magnetic resonance imaging (rs-fMRI) and independent component analysis (ICA), the present study examined functional network coupling between prefrontal and limbic systems and links to self-control and substance use onset in adolescents. Results suggest that negative network coupling (anti-correlated temporal dynamics) between the right fronto-parietal and limbic resting state networks is associated with greater self-control and later substance use onset in adolescents. These findings increase our understanding of the developmental importance of prefrontal-limbic circuitry for adolescent substance use at the resting-state network level.     

Value of gadolinium in brain MRI examinations for developmental delay

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.     

Neurodevelopmental and behavioral issues in Williams syndrome

Much existing research on Williams syndrome (WS) has focused on the individuals' unusual cognitive profile, with less emphasis placed on the developmental and neural underpinnings of the disorder. We review recent findings from brain imaging and begin to discuss links from these data to the behavioral phenotype. Overall brain size is significantly reduced in individuals with WS, as it is in many mental retardation syndromes. However, the specific profile of deficits in WS, particularly the visuospatial deficits, appears to be linked to parietal lobe abnormalities. Results from both genetic and brain imaging studies have provided useful insights into WS neurobiology. However, future work needs to remediate the lack of studies investigating developmental processes.     

Developmental venous anomaly in association with neuromigrational anomalies

This report describes a male neonate with unusual neuroradiologic findings at birth. The patient's subsequent clinical course and the evolution of his findings on serial magnetic resonance imaging and magnetic resonance venograms are consistent with a developmental venous anomaly. The case underscores the association of developmental venous anomalies with neuromigrational disorders such as polymicrogyria and nonschizencephalic clefts. It also emphasizes the importance of recognizing this problem for prognostication and treatment.     

Cavernous and Venous Angiomas of the Central Nervous System,Neuroimaging and Clinical Controversies; Neuroimaging and Clinical Controversies

Cavernous and venous angiomas of the brain are often incidental findings on computed tomography (CT) and magnetic resonance imaging (MRI) scans of patients with unrelated signs and symptoms. Cavernous angiomas can cause hemorrhage or seizures. The venous angioma itself is a developmental anomaly and as such has only a slight predisposition to rupture. Cavernous and venous angiomas have distinct CT and MRI characteristics, which facilitate their diagnosis. No therapy is usually indicated for venous angiomas. On the other hand, extirpation of cavernous angiomas is the usual treatment of choice.     

Focal cortical dysplasia: prevalence, clinical presentation and epilepsy in children and adults

Focal cortical dysplasias (FCD) are defined as circumscribed malformations of cortical development. They result from an impairment of neuronal proliferation, migration and differentiation. In the diagnosis of focal epilepsy FCD prevalence ranges between 5% and 25%, depending on patient collective and imaging techniques. Several 'cryptogenic' epilepsies may be caused by FCD but have not been diagnosed because of the lack of high-quality magnetic resonance imaging assessment. Retrospective analysis of patients who have undergone epilepsy surgery can be biased because of the fact that they represent a mere subset of potential FCD diagnoses. Epilepsy typically manifests within the first years of life, but has been documented up to the age of 60 years. Cognitive impairment commonly accompanies early onset. Epilepsy is often refractory to antiepileptic drug (AED) treatment. Clinical observations and pathophysiological findings illustrate intrinsic epileptogenicity. Upregulation of drug transporter proteins has been found in FCD tissue. There is no specific drug treatment in FCD, as any AED used in focal epilepsy could prove effective. A sequential AED therapy should be designed individually and take side effects as well as developmental progresses into consideration. Fifty to sixty-five percent of FCD patients are rendered seizure-free after surgery. Presurgical evaluation should be initiated after two unsuccessful AED trials. Both risks and potential benefits regarding seizure control and developmental impairment need to be considered on an individual basis when deciding between surgical intervention and conservative treatment. Current knowledge on epilepsy course and psychomotor development in FCD is limited in the absence of qualified long-term studies combining imaging with cognitive evaluation.     

Neuroimaging studies of normal brain development and their relevance for understanding childhood neuropsychiatric disorders

ObjectiveTo review the maturational events that occur during prenatal and postnatal brain development and to present neuroimaging findings from studies of healthy individuals that identify the trajectories of normal brain development.MethodHistological and postmortem findings of early brain development are presented, followed by a discussion of anatomical, diffusion tensor, proton spectroscopy, and functional imaging findings from studies of healthy individuals, with special emphasis on longitudinal data.ResultsEarly brain development occurs through a sequence of major events, beginning with the formation of the neural tube and ending with myelination. Brain development at a macroscopic level typically proceeds first in sensorimotor areas, spreading subsequently and progressively into dorsal and parietal, superior temporal, and dorsolateral prefrontal cortices throughout later childhood and adolescence. These patterns of anatomical development parallel increasing activity in frontal cortices that subserves the development of higher-order cognitive functions during late childhood and adolescence. Disturbances in these developmental patterns seem to be involved centrally in the pathogenesis of various childhood psychiatric disorders including childhood-onset schizophrenia, attention-deficit/hyperactivity disorder, developmental dyslexia, Tourette's syndrome, and bipolar disorder.ConclusionsAdvances in imaging techniques have enhanced our understanding of normal developmental trajectories in the brain, which may improve insight into the abnormal patterns of development in various childhood psychiatric disorders.     

Nontumoral occipitotemporal epilepsy: localizing findings and surgical outcome

We describe a syndrome of medically intractable occipitotemporal epilepsy of nontumoral developmental origin and its treatment by surgery. From our epilepsy surgery database of 1988 to 1996, we selected all patients without neoplasm who had at least two characteristics localizing to the occipital lobe (clinical symptoms, interictal focus, ictal onset, or a lesion on magnetic resonance imaging scanning) and one to the temporal lobe (interictal spikes or seizure onset). We discuss seizure characteristics, electroencephalographic (EEG), magnetic resonance imaging, positron emission tomographic, and single-photon emission computed tomographic findings, pathological findings, surgical approach, outcome from resective surgery, and implications for pathophysiology. Sixty-nine percent of our 16 patients with occipitotemporal syndrome had neuronal migration disorder, suggesting a developmental etiology of this entity. Initial signs or symptoms suggested occipital lobe seizure onset in 13 of 16 patients. On scalp EEG, interictal spikes were localized to the temporal lobe in 9 and to the occipital lobe in 1; seizure onset was poorly localized. Intracranial EEG localized seizure onset to the area of temporo-occipital junction in 77% of patients. Positron emission tomography and single-photon emission computed tomography showed occipital and temporal or widespread deficits, and neuropsychological performance was diffusely abnormal. Surgical results were best with occipital and temporal resections, but sometimes satisfactory after occipital resection even with temporal (ipsilateral) EEG findings. Temporal resection with hippocampectomy uniformly failed to control seizures. An often refractory, probably developmental epileptic syndrome with regional occipitotemporal distribution can be diagnosed by a specific constellation of findings, which has implications for treatment and pathophysiology.     

Vertebral Artery Anomaly Causing C2 Suboccipital Neuralgia,Relieved by Neurovascular Decompression

We report imaging and surgical findings of a symptomatic 40‐year‐old male with an anomalous left vertebral artery. MR, CT myelography, angiography, and intraoperative photos demonstrate the vertebral artery entering the thecal sac at the C1‐C2 intervertebral foramen and compressing the dorsal C2 nerve rootlets against the cord. Open microvascular decompression alleviated the patient's long‐standing suboccipital and posterior cervical neck pain. An embryologic review of the vertebral and lateral spinal artery systems reveals possible developmental explanations for this variant. Intradural course of the vertebral artery at C2 is one of the few symptomatic developmental vertebral artery anomalies. Recognition of this condition is important because surgical intervention can alleviate associated neck pain.     

Comparison of cerebral volume in children aged 18-22 and 36-47 months born preterm and term

Studies investigating differences in regional brain volumes in children born preterm and term during early childhood are limited. Neuroimaging could help understand patterns of deficit in children born preterm and target areas of development associated with these regions. The goal of this study was to identify differences in regional brain volume at 2 different ages using magnetic resonance imaging in preterm and term children. Magnetic resonance imaging and developmental testing occurred in children 18 to 22 months old (16 preterm and 10 term children) and 36 to 47 month old (12 preterm and 10 term children). There were significant differences between the 4 groups in the parietal region, cerebral white matter, third ventricle, and lateral ventricle. Correlations between regional cerebral volume and developmental testing were explored for the third and lateral ventricles. Our findings indicate that in young children differences in regional cerebral volume are due to both maturation and prematurity.     

Cerebral palsy, developmental delay, and epilepsy after neonatal seizures

This study sought to identify clinical prognostic factors for cerebral palsy, global developmental delay, and epilepsy in term infants with neonatal seizures. We completed a retrospective analysis of 120 term infants who experienced clinical neonatal seizures at a single academic pediatric neurology practice. Logistic regression analysis determined the significant independent prognostic (P < 0.05) indicators of cerebral palsy, global developmental delay, and epilepsy. Fifty-four (45%) infants were never diagnosed with a neurodevelopmental abnormality, whereas 37 (31%) manifested cerebral palsy, 51 (43%) manifested global developmental delay, and 38 (32%) manifested epilepsy. Global developmental delay was present in 92% of the children who manifested spastic quadraparetic cerebral palsy. Seizure type, seizure onset, electroencephalographic background findings, and 5-minute Apgar scores constituted independent predictors of cerebral palsy. None of the children who manifested less than two predictors developed the disorder. For global developmental delay, predictors included method of delivery, seizure onset, electroencephalographic background findings, and etiology. Only one infant (2%) who manifested less than two predictors exhibited global developmental delay. For epilepsy, predictors included seizure type and administration of a second antiepileptic drug. Only one infant (3%) who manifested neither predictor developed the disease.     

Malformations of cortical development and epilepsy, part 1: diagnosis and classification scheme

Malformations of cortical development (MCDs) are a common cause of epilepsy, although seizures are not always the most prominent neurologic manifestation of these disorders. In localization-related epilepsy, certain features should create a strong suspicion that an MCD is the underlying cause; these include developmental delay and static focal neurologic deficits, a family history of developmental delay or epilepsy, frequent seizures from onset, and episodes of focal status epilepticus. MCDs can be classified according to a number of different criteria emphasizing clinical phenotype, imaging findings, pathology, or genetic defects. The overall classification of MCDs is based on the 3 fundamental events of cortical formation: 1) proliferation of neurons and glia in the ventricular and subventricular zones; 2) multidirectional migration of immature but postmitotic neurons to the developing cerebral cortex; and 3) cortical organization. Among the most common and distinct syndromes and entities affecting patients with MCDs and epilepsy are focal cortical dysplasia, hemimegalencephaly, tuberous sclerosis, classical lissencephaly, periventricular nodular heterotopia, focal subcortical heterotopia, polymicrogyria, and schizencephaly, all of which are discussed herein.     

Siblings with cystic leukoencephalopathy and megalencephaly

Cystic leukoencephalopathy with megalencephaly is a newly described entity with mild clinical involvement. Patients suffer from developmental problems and seizures in childhood. Progression is gradual into adulthood. Typical magnetic resonance imaging findings include subcortical cysts and diffuse leukoencephalopathy. The etiology is unknown with possibly autosomal-recessive inheritance. We present two pairs of siblings with this disease and emphasize the characteristic and variable patterns even within the same family.     

Neurological, electrophysiological and MRI abnormalities in infants with extensive cystic leukomalacia

Twenty infants, diagnosed by cranial ultrasound as having extensive cystic leukomalacia, had visual evoked responses (VER) and electroencephalograms (EEG) in the neonatal period and MRI scans later in infancy. The early ultrasound findings and results from the electrophysiological tests were correlated with later MRI findings and functional abilities. In infants with periventricular leukomalacia (PVL), the cysts were usually no longer visible by ultrasonography, beyond 40 weeks postmenstrual age (PMA), but later MRI scans showed a consistent pattern of delayed myelination around the irregularly dilated occipital horns of the lateral ventricles. VER's were present in the neonatal period and vision was maintained, although all infants developed a marked squint. EEG's were either normal or abnormal initially, but improvement was noted within several weeks. In those with subcortical or mixed lesions, cysts were noted to persist beyond 40 weeks PMA. Later MRI scans showed very poor myelination, with poor progress on subsequent scans and cortical atrophy. VER's were absent and all infants later became cortically blind. EEG's were severely abnormal and recovery was very poor. The infants with PVL developed spastic diplegia with moderate developmental delay, while those with mixed or subcortical lesions developed quadriplegia with severe mental retardation. An integrated approach, consisting of ultrasound imaging and electrophysiological recordings in the neonatal period and MRI imaging later in infancy, may provide a more reliable prediction of the pattern of later deficits.     

Discordant Occurrence of Cerebral Unilateral Heterotopia and Epilepsy in Monozygotic Twins

Summary: Cerebral developmental malformations are increasingly recognized as a cause of epilepsy. Magnetic resonance imaging (MRI) has advanced our understanding of these disorders and their relation to epilepsy. We report the occurrence of discordant unilateral heterotopia and epilepsy in monozygotic twins. The affected individual developed intractable focal seizures at age 16 years. Mild cognitive difficulties had been present in early life. Evaluation showed right hemisphere EEG epileptogenic abnormalities, and the MRI scan showed massive right hemisphere heterotopia. EEG and MRI examinations in the patient's twin brother were normal. These findings suggest that the development of some developmental brain malformations and epilepsy is strongly influenced by nongenetic factors such as anenvironmental insult.     

Toward dysfunctional connectivity: a review of neuroimaging findings in pediatric major depressive disorder

Child and adolescent psychiatric neuroimaging research typically lags behind similar advances in adult disorders. While the pediatric depression imaging literature is less developed, a recent surge in interest has created the need for a synthetic review of this work. Major findings from pediatric volumetric and functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity studies converge to implicate a corticolimbic network of key areas that work together to mediate the task of emotion regulation. Imaging the brain of children and adolescents with unipolar depression began with volumetric studies of isolated brain regions that served to identify key prefrontal, cingulate and limbic nodes of depression-related circuitry elucidated from more recent advances in DTI and functional connectivity imaging. Systematic review of these studies preliminarily suggests developmental differences between findings in youth and adults, including prodromal neurobiological features, along with some continuity across development.     

Alexander's disease: clinical, pathologic, and genetic features

Alexander's disease, a rare and fatal disorder of the central nervous system, most commonly affects infants and young children but can also occur in older children and sometimes adults. In infants and young children, it causes developmental delay, psychomotor retardation, paraparesis, feeding problems, usually megalencephaly, often seizures, and sometimes hydrocephalus. Juvenile cases often do not have megalencephaly and tend to have predominant pseudobulbar and bulbar signs. In both groups, characteristic magnetic resonance imaging findings have been described. In adult cases, the signs are variable, can resemble multiple sclerosis, and might include palatal myoclonus. In all cases, the examination of brain tissue shows the presence of widely distributed Rosenthal fibers. Almost all cases have recently been found to have a heterozygous, missense, point mutation in the gene for glial fibrillary acidic protein, which provides a new diagnostic tool. In most cases, the mutation appears to occur de novo, not being present in either parent, but some adult cases are familial.