Pediatric Leigh Syndrome: Neuroimaging Features and Genetic Correlations.

The neurodiagnostic criteria of Leigh syndrome have not yet been clearly redefined based on the expanding of molecular etiologies. We aimed to analyze 20 years of clinical, genetic, and magnetic resonance studies from our Leigh syndrome cohort to provide a detailed description of central nervous system lesions in Leigh syndrome and their biological evolution in view of their genetic and clinical findings. Our study adds new neurodiagnostic insights to the current knowledge of Leigh syndrome, including association with overlapping syndromes, and the correlation of pathogenic genetic variants with neuroimaging phenotypes. ANN NEUROL 2020;88:218-232.

Isocaloric Ketogenic Diet in Adults with High-Grade Gliomas: A Prospective Metabolic Study.

The use of the ketogenic diet (KD) as an adjuvant therapy in high-grade gliomas (HGG) is supported by preclinical studies, but clinical data on its effects on metabolism are currently lacking. In this study, we describe the effects of a KD on glucose profile, ketonemia, energy metabolism, and nutritional status, in adults affected by HGG. This was a single-arm prospective study. An isocaloric 3:1 KD was administered for 1 mo. Glucose profile was assessed by using fasting glycemia, insulin, and glycated hemoglobin. To evaluate ketonemia changes, a hand-held ketone meter was used from home. Energy metabolism was assessed by indirect calorimetry. Nutritional status was evaluated through changes in body composition and in lipid and hepatic profile. No changes in fasting glycemia were observed; however, insulinemia dropped to half of baseline levels. The KD shifted the metabolism, rising ketonemia and decreasing glucose oxidation rate to a quarter of the initial values. Moreover, the KD was generally safe. One-month intervention with the KD was able to act upon key metabolic substrates potentially involved in HGG metabolism. The lack of a significant reduction in fasting glycemia should be investigated in future studies.

Novel in vivo depiction of optic nerves hemorrhages in child abuse: a 3D-SWI pilot study.

PURPOSE: Until now, the diagnosis of optic nerves hemorrhages in abusive head trauma (AHT) has been obtained only in the postmortem setting. The aim of the IRB-approved study was to assess the presence of optic nerves hemorrhages in AHT patients using 3D-SWI. METHODS: Thirteen children with a final confirmed multidisciplinary diagnosis of AHT underwent coronal and axial 3D-SWI imaging of the orbits. The presence of optic nerve sheath (ONS) hemorrhages was defined by thickening and marked 3D-SWI hypointensity of the ONS, resulting in mass effect upon the CSF space. Optic nerve (ON) hemorrhages were defined by areas of susceptibility artifacts in the ON parenchyma. Superficial siderosis was defined by susceptibility artifact coating the ON. Furthermore, data about post-traumatic deformity of the ONS at the head of the optic nerve were collected. RESULTS: The average age of the population was 7.9 ± 5.9 months old. The average GCS was 11.8 ± 4.5. The male to female ratio was 7:6. ONS hemorrhages were identified in 69.2% of cases. Superficial siderosis and ON hemorrhages were identified in 38.5 and 76.9% of cases, respectively. 3D-SWI also depicted traumatic deformity of the ONS at the level of the optic nerve head in 10 cases (76.9%). No statistical correlations were identified between RetCam findings and 3D-SWI findings or GCS and ON hemorrhages. CONCLUSION: This research shows that dedicated MRI with volumetric SWI of the orbits can depict hemorrhages in the ON, ONS, and ONS injury, in AHT victims.

Magnetic resonance imaging of optic nerve and optic sheath hemorrhages in child abuse.

In abusive head trauma victims, optic nerves and optic sheath hemorrhages are commonly associated with retinal hemorrhages. Until now, optic nerve and optic nerve sheath hemorrhages related to abusive head trauma have been identified by exenteration and soft-tissue sectioning during postmortem examination. In 2013, we proposed the use of tailored high-resolution susceptibility-weighted imaging (SWI) MRI sequences to depict retinal hemorrhages in lieu of the gold standard dilated fundus exam, in select patients, and in 2017 we showed how the same high-resolution sequences used in the coronal plane can depict ruptured bridging veins in abusive head trauma. This paper describes the new potential diagnostic application of high-resolution axial and coronal SWI in the diagnosis of optic nerve and optic sheath hemorrhages.

Venous injury in pediatric abusive head trauma: a pictorial review.

Abusive head trauma (AHT) is the leading cause of fatal head injuries in children younger than 2 years. An intracranial pathology can exist even in the setting of a normal physical exam. A delay in the diagnosis of AHT can have serious life-threatening consequences for the child and increases the potential the child will be abused again. In this article, we review the traumatic subdural hematoma as well as various morpho-structural patterns of shearing injuries and thrombosis of intracranial bridging veins. This work serves as a summary of patterns of imaging features of intracranial venous injury in AHT, as described in the literature, to facilitate familiarity and early detection of abusive head trauma in the pediatric population. Essentially, in AHT there is a traumatic injury to the bridging vein with either partial or complete tear. This can secondarily result in thrombosis at the terminal end of the bridging vein with blood clots adjacent to the bridging vein.

Neuroimaging of retinal hemorrhage utilizing adjunct orbital susceptibility-weighted imaging.

Retinal hemorrhages are an integral part of the evaluation of abusive head trauma (AHT). Timely detection of retinal hemorrhage not only facilitates the diagnosis of AHT, but has the potential to prevent further abuse to the child and the siblings and to identify the abuser. The gold standard for diagnosing retinal hemorrhage is a dilated fundoscopy exam, which requires pharmacological dilation. As such, there is a small percentage of patients for whom the dilated fundoscopy exam might be delayed. Evolving literature suggests that MRI, specifically susceptibility-weighted imaging (SWI), of the orbits might provide an alternative diagnostic tool for noninvasively detecting retinal hemorrhages, particularly when there is a delay in administering the dilated fundoscopy exam. In this paper we review the utility of SWI for detecting retinal hemorrhages in abusive head trauma, including discussion of diagnostic limitations and future research.

The Presence of Anemia in Children with Abusive Head Trauma.

OBJECTIVES: To evaluate the incidence of anemia in patients with abusive head trauma (AHT), noninflicted traumatic brain injury (TBI), and physical abuse without AHT and the effect of anemia on outcome. STUDY DESIGN: In a retrospective, single-center cohort study, we included children under the age of 3 years diagnosed with either AHT (n = 75), noninflicted TBI (n = 77), or physical abuse without AHT (n = 60) between January 1, 2014, and December 31, 2016. Neuroimaging was prospectively analyzed by pediatric neuroradiologists. Primary outcome was anemia at hospital presentation. Secondary outcomes included unfavorable outcome at hospital discharge, defined as a Glasgow Outcome Scale between 1 and 3, and intracranial hemorrhage (ICH) volume. RESULTS: Patients with AHT had a higher rate of anemia on presentation (47.3%) vs noninflicted TBI (15.6%) and physical abuse without AHT (10%) (P < .001). Patients with AHT had larger ICH volumes (33.3 mL [10.1-76.4 mL] vs 1.5 mL [0.6-5.2 mL] ; P < .001) and greater ICH/total brain volume percentages than patients with noninflicted TBI (4.6% [1.4-8.2 %] vs 0.2% [0.1-0.7%]; P < .001). Anemia was associated with AHT (OR, 4.7; 95% CI, 2.2-10.2) and larger ICH/total brain volume percentage (OR, 1.1; 95% CI, 1.1-1.2) in univariate analysis. Unfavorable outcome at hospital discharge was associated with anemia (OR, 4.4; 95% CI, 1.6-12.6) in univariate analysis, but not after controlling for covariates. CONCLUSIONS: Patients with AHT were more likely to present to the hospital with anemia and increased traumatic ICH volume than patients with noninflicted TBI or physical abuse without AHT. Children with anemia and AHT may be at increased risk for an unfavorable outcome.

A computational framework for the detection of subcortical brain dysmaturation in neonatal MRI using 3D Convolutional Neural Networks.

Deep neural networks are increasingly being used in both supervised learning for classification tasks and unsupervised learning to derive complex patterns from the input data. However, the successful implementation of deep neural networks using neuroimaging datasets requires adequate sample size for training and well-defined signal intensity based structural differentiation. There is a lack of effective automated diagnostic tools for the reliable detection of brain dysmaturation in the neonatal period, related to small sample size and complex undifferentiated brain structures, despite both translational research and clinical importance. Volumetric information alone is insufficient for diagnosis. In this study, we developed a computational framework for the automated classification of brain dysmaturation from neonatal MRI, by combining a specific deep neural network implementation with neonatal structural brain segmentation as a method for both clinical pattern recognition and data-driven inference into the underlying structural morphology. We implemented three-dimensional convolution neural networks (3D-CNNs) to specifically classify dysplastic cerebelli, a subset of surface-based subcortical brain dysmaturation, in term infants born with congenital heart disease. We obtained a 0.985 ±â€¯0. 0241-classification accuracy of subtle cerebellar dysplasia in CHD using 10-fold cross-validation. Furthermore, the hidden layer activations and class activation maps depicted regional vulnerability of the superior surface of the cerebellum, (composed of mostly the posterior lobe and the midline vermis), in regards to differentiating the dysplastic process from normal tissue. The posterior lobe and the midline vermis provide regional differentiation that is relevant to not only to the clinical diagnosis of cerebellar dysplasia, but also genetic mechanisms and neurodevelopmental outcome correlates. These findings not only contribute to the detection and classification of a subset of neonatal brain dysmaturation, but also provide insight to the pathogenesis of cerebellar dysplasia in CHD. In addition, this is one of the first examples of the application of deep learning to a neuroimaging dataset, in which the hidden layer activation revealed diagnostically and biologically relevant features about the clinical pathogenesis. The code developed for this project is open source, published under the BSD License, and designed to be generalizable to applications both within and beyond neonatal brain imaging.

Contrast-enhanced 3-dimensional Fluid-attenuated Inversion Recovery Sequences Have Greater Sensitivity for Detection of Leptomeningeal Metastases in Pediatric Brain Tumors Compared With Conventional Spoiled Gradient Echo Sequences.

Postcontrast 3-dimensional fluid-attenuated inversion recovery (3D-FLAIR) sequences have reduced vascular and flow-related artifacts and high sensitivity to low gadolinium concentrations. We compared the performance of postcontrast spoiled gradient echo images to 3D-FLAIR in the detection of leptomeningeal metastases in 47 pediatric patients with brain tumors. We found 10 cases with more leptomeningeal signal abnormalities on 3D-FLAIR. Overall there were significantly more lesions on 3D-FLAIR than spoiled gradient echo sequences. We believe the increased detection of leptomeningeal signal abnormality is due to increased sensitivity for low concentrations of gadolinium in regions of early blood brain barrier breakdown. Our study was limited by the lack of leptomeningeal metastases in cerebrospinal fluid sampling. We plan to conduct future studies which will determine whether the time-based concentration of gadolinium affects the performance and results. Future studies will also require more cases of pathology-proven leptomeningeal disease.

Presenting Characteristics Associated With Outcome in Children With Severe Traumatic Brain Injury: A Secondary Analysis From a Randomized, Controlled Trial of Therapeutic Hypothermia.

OBJECTIVES: To identify injury patterns and characteristics associated with severe traumatic brain injury course and outcome, within a well-characterized cohort, which may help guide new research and treatment initiatives. DESIGN: A secondary analysis of a phase 3, randomized, controlled trial that compared therapeutic hypothermia versus normothermia following severe traumatic brain injury in children. SETTING: Fifteen sites in the United States, Australia, and New Zealand. PATIENTS: Children (< 18 yr old) with severe traumatic brain injury. MEASUREMENTS AND MAIN RESULTS: Baseline, clinical, and CT characteristics of patients (n = 77) were examined for association with mortality and outcome, as measured by the Glasgow Outcome Scale-Extended Pediatric Revision 3 months after traumatic brain injury. Data are presented as odds ratios with 95% CIs. No demographic, clinical, or CT characteristic was associated with mortality in bivariate analysis. Characteristics associated with worse Glasgow Outcome Scale-Extended Pediatric Revision in bivariate analysis were two fixed pupils (14.17 [3.38-59.37]), abdominal Abbreviated Injury Severity score (2.03 [1.19-3.49]), and subarachnoid hemorrhage (3.36 [1.30-8.70]). Forward stepwise regression demonstrated that Abbreviated Injury Severity spine (3.48 [1.14-10.58]) and midline shift on CT (8.35 [1.05-66.59]) were significantly associated with mortality. Number of fixed pupils (one fixed pupil 3.47 [0.79-15.30]; two fixed pupils 13.61 [2.89-64.07]), hypoxia (5.22 [1.02-26.67]), and subarachnoid hemorrhage (3.01 [1.01-9.01]) were independently associated with worse Glasgow Outcome Scale-Extended Pediatric Revision following forward stepwise regression. CONCLUSIONS: Severe traumatic brain injury is a clinically heterogeneous disease that can be accompanied by a range of neurologic impairment and a variety of injury patterns at presentation. This secondary analysis of prospectively collected data identifies several characteristics associated with outcome among children with severe traumatic brain injury. Future, larger trials are needed to better characterize phenotypes within this population.

Use of neuroimaging measurements of optic nerve sheath diameter to assess intracranial pressure in craniosynostosis.

PURPOSE: This study aims to evaluate accuracy of optic nerve sheath diameter (ONSD) measurements obtained by magnetic resonance imaging (MRI) in patients with craniosynostosis (CS) for detection of high intracranial pressure (ICP) and to correlate MRI-derived ONSD measurements with those obtained by computed tomography (CT) scans in CS patients. METHODS: A retrospective review was conducted on CS patients who had MRI- and age-matched controls with normal MRI. Diagnosis of intracranial hypertension was based on presence of papilledema, direct ICP monitoring, and/or lumbar puncture. The search also included patients with MRI and CT done within 30 days apart. ONSDs were measured 3 mm behind the globe on both modalities. RESULTS: The study identified 56 CS patients (mean age 3.8 ± 3.47 years) and 49 controls (mean age 3.7 ± 3.62 years). Mean ONSD in patients with high ICP was significantly higher than in patients without high ICP (P = 0.0001) and in controls (P < 0.0001). The optimal ONSD threshold for predicting raised ICP in patients >1 year old was 6 mm (71.4% sensitivity, 89.7% specificity). Nineteen patients with 38 single-eye MRI/CT pairs were identified. Substantial agreement between both modalities resulted (r = 0.959, 95% CI 0.923-0.978), and Bland and Altman Plot analysis showed that 95% of measurements fell within limits of agreement (1.96 SD; ± 0.6 mm). CONCLUSION: In CS patients, ONSD measured by MRI represent indirect non-invasive means of ICP assessment. Both MRI and CT measurements of ONSD gave comparable results, and the use of CT-derived ONSD measurements may give some idea about ICP in CS patients.

Brain Dysplasia Associated with Ciliary Dysfunction in Infants with Congenital Heart Disease.

OBJECTIVE: To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) STUDY DESIGN: We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound scan and brain magnetic resonance imaging were obtained pre- and/or postoperatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. RESULTS: A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury but was correlated with increased extraaxial cerebrospinal fluid volume (P < .001), delayed brain maturation (P < .05), and a spectrum of subtle dysplasia including the hippocampus (P < .0078) and olfactory bulb (P < .034). Abnormal CM was associated with higher composite dysplasia score (P < .001), and both were correlated with elevated preoperative serum lactate (P < .001). CONCLUSIONS: Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks.

Thickening of the cauda equina roots: a common finding in Krabbe disease.

OBJECTIVES: Evaluation of Krabbe disease burden and eligibility for hematopoietic stem cell transplantation are often based on neuroimaging findings using the modified Loes scoring system, which encompasses central but not peripheral nervous system changes. We show that quantitative evaluation of thickened cauda equina nerve roots may improve the evaluation of Krabbe disease and therapeutic guidance. METHODS: Lumbar spine MRI scans of patients obtained between March 2013 and September 2013 were retrospectively evaluated and compared to those of controls. Quantitative evaluation of cauda equina roots was performed on the axial plane obtained approximately 5 mm below the conus medullaris. The largest nerves in the right and left anterior quadrants of the spinal canal were acquired. RESULTS: Fifteen symptomatic patients with Krabbe disease (5-44 months old) and eleven age-matched controls were evaluated. The average areas (mm(2)) of anterior right and left nerves were 1.40 and 1.23, respectively, for patients and 0.61 and 0.60 for controls (differences: 0.79 and 0.63; p < 0.001). CONCLUSIONS: Cauda equina nerve root thickening is associated with Krabbe disease in both treated and untreated patients. Adding lumbar spine MRI to the current neurodiagnostic protocols, which fails to account for peripheral nerve abnormalities, will likely facilitate the diagnosis of Krabbe disease. KEY POINTS: • Neuroimaging is valuable for evaluating cauda equina nerve abnormality in Krabbe disease • MRI can be used to quantitatively evaluate cauda equina nerve thickening • Lumbar MRI could be useful for diagnosis and treatment monitoring of Krabbe disease.

Do dermatomyositis and polymyositis affect similar thigh muscles? A comparative MRI-based study.

OBJECTIVES: Dermatomyositis (DM) and polymyositis (PM) commonly cause weakness of the thigh muscles. However, it is debated whether DM and PM affect similar thigh muscles. Muscle oedema on fat-suppressed MRI sequences is thought to represent active inflammation. In this study, we aimed to assess which thigh muscle groups are preferentially inflamed in DM and PM, respectively, using short-tau inversion-recovery MRI sequences. METHODS: We analysed 71 patients from 2 Rheumatology centres, 31 with DM and 40 with PM diagnosed according to the Bohan and Peter criteria. MRI oedema (1=present, 0=absent) was assessed bilaterally on fat-suppressed sequences in 17 pelvic floor and thigh muscles. An MRI oedema score (range 0-17) was calculated by adding the separate scores bilaterally and dividing them by two. Inter-rater variability was assessed by intraclass correlation coefficient. Fisher's exact test was used to compare binomial data. RESULTS: Age and gender ratio were similar in patients with DM and PM. Disease duration (months, mean±SD) was shorter (20±31) in DM than in PM (53±69) (p=0.02). The intraclass correlation coefficient between the radiologists involved was 0.78. Muscle oedema was more common in DM than in PM except in the posterior thigh muscles. In particular, 68% of patients with DM had involvement of at least one anterior thigh muscle versus 38% of patients with PM (p=0.02). CONCLUSIONS: Compared with PM, DM affects more thigh muscles, except those of the posterior compartment, which are equally involved in both disorders. These findings may be useful to target physiotherapy at the more frequently affected muscles.

Delayed activation of the primary orbitofrontal cortex in post-traumatic anosmia.

BACKGROUND: Functional magnetic resonance imaging may help in elucidating the pathophysiology of post-traumatic anosmia. METHOD: Using an fMRI olfactory stimulus paradigm, this study compared BOLD activation of the brain in a 21-year old male research subject with post-traumatic anosmia and a 19-year old male normal healthy control participant. OUTCOMES: A delayed activation of the primary orbitofrontal cortex was found in the subject with traumatic anosmia, which may represent a crucial pathophysiological mechanism in the subject with traumatic anosmia due to axonal injury or traumatic transection at the lamina cribrosa level. DISCUSSION: In healthy subjects the activation of secondary cortical areas may be due to the habituation effect in the primary olfactory cortex. This raises the possibility that, in the absence of secondary activation areas-that may act as a feed-back habituation or desensitization in the patient-one of the primary response areas is activated over the longer period of stimulation. The failed activation of these secondary areas in the patient may cause a feed-back habituation or desensitization in the patient and could also play a role in the disturbed perception of odours.

Severe CNS involvement in WWOX mutations: Description of five new cases.

Recently, mutations in WWOX have been identified in the setting of central nervous system (CNS) disorders, highlighting a previously unrevealed role of this gene in the normal development and function of the CNS. In this report, we add five patients from two seemingly unrelated families presenting with a primarily neurological phenotype. All the children were product of consanguineous marriages. Whole exome sequencing revealed the same homozygous mutation (NM_016373.3:c.606-1G>A) of WWOX in all five patients. All patients and carriers in the family share the same haplotype indicating the families are in fact related to one another. The clinical presentation included progressive microcephaly, early onset of spasticity in the first 3 months of life, intractable epilepsy, severe failure to thrive, and profound developmental delay. Retinopathy was observed in two patients. All five patients died before their third birthday. Neuroimaging showed extensive neurodegeneration characterized by periventricular white matter volume loss and atrophy of the corpus callosum. Additional degeneration selectively affecting the mediodorsal nucleus of the thalamus was observed in one patient. Our findings in five new patients affected by WWOX mutation with early infantile phenotype confirm the features of the disease represented by early infantile epileptic encephalopathy. We suggest that neuroimaging in these patients reveals a characteristic pattern of neurodegeneration in which the cerebellum is spared that could help with early diagnosis in the appropriate clinical setting.

Pseudoprogression of low-grade gliomas after radiotherapy.

BACKGROUND: Increasing mass effect following radiation therapy (RT) in patients with low-grade gliomas (LGGs) can be mistaken for tumor progression and/or malignant degeneration. Distinguishing pseudoprogression (PP) from true progression is crucial, with vastly different treatment approaches and prognoses. PROCEDURE: Patients treated with RT for LGGs through the Children's Hospital of Pittsburgh Neuro-Oncology Program are considered to have PP and managed conservatively if they develop increased mass effect within 3 years of RT. Pre-RT tumor area was compared to the maximum tumor size following RT and the size on the last follow-up scan by a central reviewer. RESULTS: Twenty-four children, median age 13 years, received external beam RT for LGG between March 2000 and August 2011. Thirteen patients (54.2%) developed an increase in tumor size compared to baseline beginning at a median of 6 months after RT and lasting for a median of 2.1 years (range 6.5 months to 5.1 years). Maximum tumor enlargement occurred at a median of 8 months after RT, with a range (5 months to 4.2 years). In all 13 cases, the tumor eventually decreased in size without additional anti-tumor therapy. Two patients (8.3%) developed true tumor progression. With a median follow-up of 4.9 years (range 1.0-12.4 years), all patients are alive. CONCLUSIONS: Pseudoprogression occurred in more than half of the children with LGG following RT, typically beginning within 8 months and often running a very protracted course. Late presentations can also occur.

Arterial blood pressure but not serum albumin concentration correlates with ADC ratio values in pediatric posterior reversible encephalopathy syndrome.

INTRODUCTION: Posterior reversible encephalopathy syndrome (PRES) is a clinical-radiological entity affecting both adults and children characterized by neurotoxicity often in setting of hypertension coupled with distinct brain magnetic resonance imaging features. Decreased serum albumin level has been suggested to correlate with the presence of vasogenic brain edema in adult PRES. Serum albumin has thus been hypothesized to protect against neurotoxicity in PRES by reducing vasogenic brain edema through its role in maintaining plasma osmotic pressure and endothelial integrity. The purpose of our study was to investigate if such correlation between decreased serum albumin level and PRES-related vasogenic edema could be found in children. METHODS: We conducted a retrospective study of 25 pediatric patients diagnosed with PRES. Underlying clinical conditions, presenting symptoms, blood pressures, and serum albumin levels at onset of symptoms were collected. Brain MR imaging studies were reviewed. We used a quantitative method to evaluate the degree of vasogenic edema by measuring apparent diffusion coefficient (ADC) values of the T2-FLAIR hyperintense brain lesions. RESULTS: No significant correlation was found between serum albumin level and degree of PRES-related vasogenic edema. A significant correlation was found between elevated blood pressure and degree of vasogenic edema in the temporal lobes (p = 0.02 and 0.04, respectively) but not in the other cerebral lobes or cerebellum. CONCLUSIONS: Our initial results suggest blood pressure, not serum albumin level, as a main biomarker for brain edema in children with PRES. Thus, our study does not suggest a protective role of serum albumin against PRES-related neurotoxicity in children.

Bilateral symmetrical basal ganglia and thalamic lesions in children: an update (2015).

INTRODUCTION: In children, many inherited or acquired neurological disorders may cause bilateral symmetrical signal intensity alterations in the basal ganglia and thalami. METHODS: A literature review was aimed at assisting neuroradiologists, neurologists, infectious diseases specialists, and pediatricians to provide further understanding into the clinical and neuroimaging features in pediatric patients presenting with bilateral symmetrical basal ganglia and thalamic lesions on magnetic resonance imaging (MRI). RESULTS: We discuss hypoxic-ischemic, toxic, infectious, immune-mediated, mitochondrial, metabolic, and neurodegenerative disorders affecting the basal ganglia and thalami. CONCLUSION: Recognition and correct evaluation of basal ganglia abnormalities, together with a proper neurological examination and laboratory findings, may enable the identification of each of these clinical entities and lead to earlier diagnosis.