Brain Magnetic Resonance Imaging Abnormalities Research Articles

Medication-induced changes on magnetic resonance imaging of the brain.

In this review the authors focus on abnormal brain magnetic resonance imaging caused by drugs given to patients in any age group for any disease. The review includes viral infections with fever in children/infections in general, epilepsy, psychiatric diseases, multiple sclerosis, neoplasms, bone marrow/organ transplantations, total parenteral nutrition, vaccinations, oral contraceptives and other prothrombotic drugs, and gadolinium deposition. Knowledge of patients' diseases and medications they receive is crucial to establish the correct diagnosis. The absence of these data in a referral for a brain MRI scan can result in completely wrong suspicions and unleash unnecessary, complicated, time-consuming and expensive diagnostics, causing additional stress in patients and their guardians.

Seizure recurrence following the first unprovoked seizure: Risk factors among children in UAE.

In a retrospective study of paediatric and adolescent patients in Abu Dhabi, UAE, who experienced their first unprovoked seizure between March 2016 and March 2020, with a minimum one-year follow-up, we identified significant risk factors associated with seizure recurrence. Among 317 patients, 96.2% experienced seizure recurrence, with the majority (68.8%) occurring within the first 6-month follow-up period. Notable risk factors for recurrence included focal seizures, symptomatic seizure causes, abnormal initial electroencephalogram (EEG) findings, abnormal brain magnetic resonance imaging results, and the presence of neurological disorders. Interestingly, the type of epileptiform activity in the initial EEG did not predict recurrence risk. Over a 3-year period, the overall recurrence risk was 98.4%, particularly higher in cases with symptomatic seizures compared to idiopathic (genetic) ones. These findings underscore the importance of vigilant monitoring, particularly in the early post-seizure follow-up period, and advocate for initial EEG assessments, especially in cases of remote symptomatic first unprovoked seizures.

Variants loci and phenotype correlation of TRIM8-related neuro-renal syndrome: three cases reports and literature review.

TRIM8-related neuro-renal syndrome (NRS), caused by pathogenic variants of the TRIM8 gene, is characterized by epilepsy, developmental delay (DD) and renal disorders. The severity of the neurological effects as well as the presence of renal disorders is variable among patients. Here, we report three additional patients with clinical features compatible with NRS and summarize the association between the variants' loci and phenotype of TIRM8-related NRS. A retrospective analysis was conducted for three Chinese children with NRS due to TRIM8 variants identified through whole-exome sequencing (WES). Previous reports of patients with TRIM8-related NRS were reviewed systematically. Demographic and clinical data were collected from these patients. Two de novo TRIM8 truncating variants in three NRS patients were identified in our study, including c.1327_c.1328delCCinsTG (p. Arg443*) and c.1375C>T (p.Gln459*). Our three patients all exhibited drug-resistant epilepsy and early-onset DD, and two of whom developed electrical status epilepticus during sleep (ESES). Brain magnetic resonance imaging (MRI) showed periventricular leukomalacia in one patient and normal in the other two. All three patients demonstrated nephrotic range proteinuria (NRP) or nephrotic syndrome (NS) with normal renal function during follow-up. There was a total of 27 patients with TRIM8-related NRS have been identified to date. The most common clinical features are renal diseases (89%), DD (89%), followed by epilepsy (78%). 67% of patients eventually progressed to end-stage renal disease (ESRD). Focal seizure was the most frequent seizure type (57%). 52% of patients presented drug-resistant epilepsy. 64% of patients exhibited non-specific brain MRI abnormalities. Brain atrophy was the most common change (50%). Two patients with TRIM8 variants closer to the N-terminal had neurological diseases without renal damage. Five patients with TRIM8 variants closer to the C-terminal had no severe neurological diseases. Seven patients had Gln459* variant which is the most common variant (7/27, 25.9%). The severity of the renal and neurological damage of the seven patients was variable. This study expands the number of individuals with confirmed NRS due to pathogenic variants in TRIM8. Neurological and renal phenotype with the same variant locus differed in their severity. Further research is needed to explore the relationship between genotype and phenotype of TRIM8 variants.

Clinical and neuroimaging features in neurological Wilson’s disease with claustrum lesions

According to early research, the incidence of claustrum lesions in patients with neurological Wilson’s disease (WD) was inconsistent, ranging from 1.8 to 75% on magnetic resonance imaging (MRI). Our study aims to explore the incidence, clinical presentation features, iconography features, and possible pathological mechanisms in WD patients with claustrum lesions on magnetic resonance imaging (MRI), to characterize the clinical, and brain imaging findings and possible pathological mechanisms in the patients with WD. Retrospective cases meeting the inclusion criteria were studied for analyzing MRI characteristics and associated physicochemical examination data in neurological WD patients with claustrum lesions. 443 (66.3%) with brain MRI abnormalities were screened from 668 WD patients. The three (0.7%) patients with the claustrum lesions characteristics on MRI images were: (a) “bright claustrum” in T2-weighted and FLAIR sequences, (b) bilateral symmetrical, (c) non-isolated lesions, (d) occurred only in severe neurological manifestations. The claustrum lesions are not common in neurological WD and mainly appear in cases with severe neurological symptoms. On MRI, the “bright claustrum” signs may be a radiographic marker of neuroinflammation, the features of the lesions showed bilateral symmetry, and hyperintensity signals on T2-weighted, FLAIR, and DWI.

Classification of Brain Magnetic Resonance Imaging Abnormalities and Spectrum of Neurological Findings in a Cohort with Copy Number Variation-Related Disorders

Introduction: Copy number variation (CNV) is the difference in the sequence of genomic segments, which can vary from one kilobase to several megabases. Certain CNVs have been linked to various human disorders, such as intellectual disability, multiple congenital anomalies, autism spectrum disorders, neurodegenerative and neuropsychiatric conditions, and cancer. The present study aims to classify brain magnetic resonance imaging (MRI) findings, describe neurological manifestations, and discuss the findings within the context of genotype–phenotype correlations in a cohort of patients with recurrent and nonrecurrent CNVs. Methods: A total of 21 patients with pathogenic CNV detected using microarray analysis were included in the study. Results: Analysis of the clinical findings of the patient cohort showed that 16 (76%) had microcephaly, 14 had epilepsy (66%), 20 had facial dysmorphism (95%), and all had developmental delay (100%). Novel brain MRI findings were detected in six (6/13, 46%) patients with recurrent CNV and five (5/8, 63%) patients with nonrecurrent CNV. Conclusion: CNV-related disorders should be considered in the differential diagnosis of patients with brain MRI findings suspicious for metabolic disorders. Brain MRI differences in patients with the same chromosomal deletion can be explained by the second-hit hypothesis. Additional single nucleotide variations and epigenetic factors in these cases may have led to the involvement of different regions of the brain. Revealing the phenotypic and genotypic characteristics of cases in rare disorders will contribute to the widespread use of precision medicine and genetic treatment approaches in the near future.

Immune-related encephalitis after immune checkpoint inhibitor therapy.

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature. Retrospective series of patients with immune-related encephalitis and literature review. Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3. Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.

A de novo novel variant in the MT-TD gene is associated with prominent extra-neurologic manifestations.

Defects in the mitochondrial tRNA genes cause a group of highly clinically and genetically heterogeneous disorders, which poses a challenge for clinical identification and genetic diagnosis. Here, we present a pre-school boy with a novel MT-TD variant m.7560T>C at the heteroplasmy level of 76.53% in blood, 93.34% in urine sediments, and absent in the healthy mother's blood and urine. Besides convulsions, brain magnetic resonance imaging abnormalities and high plasma lactate, the boy presented with the prominent extra-neurologic phenotype including steroid-resistant nephrotic syndrome associated with focal segmental glomerulosclerosis characterized by abnormal mitochondria in podocytes, cortical blindness, and pancreatitis. To our knowledge, this is the unique case with MT-TD m.7560T>C-related multi-organ impairments, which expands the phenotypic and mutational spectrum of primary mitochondrial diseases.

AUTOIMMUNE ENCEPHALITIS: DIAGNOSTIC AND TREATMENT APPROACH

Autoimmune encephalitis is a type of brain inflammation induced by an inappropriate immune response to a neuronal antigen, resulting in the generation of autoantibodies. Autoimmunity as important cause of encephalitis in recent years has not been much reported in Indonesia. Increased familiarity with autoimmune encephalitis among physician, not only neurologist, is extremely important for early detection. Prompt diagnosis and early immunotherapy leads to better prognosis in this potentially treatable disease, despite a long disease course. Autoimmune encephalitis is characterized by acute-subacute progressive neuropsychiatric symptoms with associated cognitive dysfunction, encephalopathy, psychiatric disorders, movement disorders and seizures, with anti-N-methyl-D-aspartate (NMDA) receptors encephalitis as the most common type. In addition to clinical features, further diagnostic investigations needed are brain magnetic resonance imaging (MRI), electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, and autoantibody testing. Challenges in establishing diagnosis include wide range of clinical symptoms, absence of abnormalities in brain MRI, unspecified EEG findings, negative antibody testing, and limited availability of antibody testing in Indonesia. This literature review discusses the recognition, diagnosis and principle of treatment of autoimmune encephalitis.

Accumulation Area of a Japanese PRNP P102L Variant Associated With Gerstmann-Sträussler-Scheinker Disease: The Ariake PRNP P102L Variant.

The coast of Kyushu Island on Ariake Sea in Japan is known to be an accumulation area for patients with a proline-to-leucine substitution mutation at residue 102 (P102L) of the human prion protein gene (PRNP), which is associated with Gerstmann-Sträussler-Scheinker disease. We designated this geographical distribution as the "Ariake PRNP P102L variant." The purpose of this study was to characterize the clinical features of this variant. We enrolled patients with the PRNP P102L variant who were followed up at the Saga University Hospital from April 2002 to November 2019. The clinical information of patients were obtained from medical records, including clinical histories, brain magnetic resonance imaging (MRI), and electroencephalography (EEG). A brain autopsy was performed on one of the participants. We enrolled 24 patients from 19 family lines, including 12 males. The mean age at symptom onset was 60.6 years (range, 41-77 years). The incidence rate of the Ariake PRNP P102L variant was 3.32/1,000,000 people per year in Saga city. The initial symptoms were ataxia (ataxic gait or dysarthria) in 19 patients (79.2%), cognitive impairment in 3 (12.5%), and leg paresthesia in 2 (8.3%). The median survival time from symptom onset among the 18 fatal cases was 63 months (range, 23-105 months). Brain MRI revealed no localized cerebellar atrophy, but sparse diffusion-weighted imaging abnormalities were detected in 16.7% of the patients. No periodic sharp-wave complexes were identified in EEG. Neuropathological investigations revealed uni- and multicentric prion protein (PrP) plaques in the cerebral cortex, putamen, thalamus, and cerebellum of one patient. Western blot analysis revealed 8-kDa proteinase-K-resistant PrP. This is the first report of the accumulation area of a PRNP P102L variant on the coast of Ariake Sea. The Ariake PRNP P102L variant can be characterized by a relatively long disease duration with sparse abnormalities in brain MRI and EEG relative to previous reports. Detailed interviews to obtain information on the birthplace and the family history of related symptoms are important to diagnosing a PRNP P102L variant.

Brain magnetic resonance imaging as predictors in pediatric anti-N-methyl-D-aspartate receptor encephalitis

ObjectiveTo investigate the associations between brain magnetic resonance imaging (MRI) changes and clinical profiles in children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. MethodsClinical data and brain MRI results of children diagnosed with anti-NMDAR encephalitis in Guangzhou Women and Children's Medical Center from October 2014 to June 2022 were retrospectively studied. ResultsA total of 143 children (Male: female 54:89) were enrolled, with a mean onset age of 6.8 years (6.8 ± 3.1). 40.6 % (58/143) of patients had abnormal initial brain MRI. Lesions in temporal lobe (34.5 %, 20/58) and frontal lobe (25.9 %, 15/58) were relatively common. Children with abnormal initial brain MRI were prone to have fever (P = 0.023), dystonia (P = 0.037), positive MOG antibodies (P = 0.015), higher cerebrospinal fluid (CSF) white blood cell count (WBC) (P = 0.019) and to receive rituximab treatment (P = 0.037). There were no significant differences in modified Rankin Scale (mRS) scores before immunotherapy, after immunotherapy and at last follow-up between the normal initial brain MRI group and abnormal group. No initial brain MRI changes were found to be associated with relapses. Brain MRI was reviewed in 72 patients at last follow-up with a median follow-up time of 25.5 months and 48.6 % (35/72) of patients had abnormal brain MRI. The mRS score of the group with normal brain MRI at last follow-up was significantly lower than that of the abnormal group. ConclusionsAbout 40.0 % of children with anti-NMDAR encephalitis had abnormal initial brain MRI. Initial brain MRI was associated with certain clinical profiles, but not with relapse and prognosis. Around half of patients had abnormal brain MRI at last follow-up and were prone to have higher mRS score.

The congenital muscular dystrophies

AbstractBackgroundCongenital muscular dystrophies (CMDs) are genetically and clinically heterogeneous inherited conditions. Onset is typically within the first year of life. Most CMDs are autosomal recessive, except for de novo dominant mutations in LMNA‐related muscular dystrophy and some collagen‐6‐associated disorders.ResultsCMD is characterized by progressive muscular weakness, hypotonia, multiple contractures with a variable degree, spinal stiffness, delay in motor milestones acquisition, and histologically dystrophic lesions. Also, some forms of CMD may feature structural and myelination abnormalities on brain magnetic resonance imaging, intellectual impairment, and structural abnormalities of the eye. Muscle biopsy specimens exhibit a dystrophic pattern, but the appearance is quite variable depending on the different stages and severity of the disorder. The prevalence of CMD is estimated to be one in 100 000 people. Over the last few years, with advances in molecular genetic diagnostics, knowledge about neuromuscular disorders, particularly CMDs, has increased dramatically. Thus, the incidence may be higher than originally thought.ConclusionThis article reviews the recent achievements related to the clinical, diagnostic, pathogenic, and therapeutic aspects of CMDs.

Correlation between Persistent Serum Lactate Elevation and Brain Magnetic Resonance Imaging Abnormalities in Children with Status Epilepticus

Purpose: This study was conducted to evaluate the correlation between persistent serum lactate elevation and brain magnetic resonance imaging (MRI) in children with status epilepticus (SE). Methods: In this prospective analytical study, serum lactate levels were measured 24 hours after episodes of SE, and brain MRI was performed within 7 to 14 days after SE termination. MRI abnormalities were classified as acute encephalopathy (AE) grade I to III. The Kruskal-Wallis test was utilized for statistical analysis. Results: The study included 42 participants with SE, of whom 85.70% were boys, with a mean age of 4.94 years. Viral encephalitis was the most common diagnosis, accounting for 47.60% of cases. Elevated serum lactate levels were detected in 71.40% of patients, and approximately 47.60% exhibited abnormal MRI findings consistent with AE grade I. The median serum lactate levels for AE grades I, II, and III were 1.50, 3.10, and 0.78 mmol/L, respectively. Two patients died, and 66.70% experienced neurologic sequelae. A significant correlation (<i>P</i>=0.021) was observed between persistent serum lactate elevation and abnormal brain MRI findings. Conclusion: In children with SE, AE grade I was the most common neuroimaging pattern observed, and persistently elevated serum lactate level was correlated with abnormal brain MRI findings.

Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes

To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18months of age. Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P<.001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P<.001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P<.001). The present study shows the complementary utility of cUS in the first 48hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

Magnetic Resonance Imaging Findings and Genetic Testing Results in Children With Congenital Corneal Opacities

This study investigates brain and globe abnormalities identified on magnetic resonance imaging (MRI) in children with congenital corneal opacities (CCO). Retrospective cohort study. Clinical notes, radiology records, and genetic testing results were reviewed for patients diagnosed with corneal opacification within the first 6 months of life at a tertiary referral academic center between August 2008 and January 2018. Ocular findings, systemic anomalies, neuroimaging, and genetic testing results were summarized. A total of 135 patients presenting at age 1 day to 12 years (mean age, 1 year) were identified. Children with bilateral CCO were more likely to have systemic disease (P = 0.018). Of the entire cohort, 43 (31.8%) patients received MRI, of whom 27 (62.8%) had abnormal brain findings and 30 (69.7%) had abnormal orbital findings. The most common abnormal brain findings were ventriculomegaly (n = 16, 59.2%) and corpus callosum abnormalities (n = 10, 37.0%) followed by brainstem/pons anomalies (n = 5, 18.5%), and cerebellar anomalies (n = 2, 7.4%). Abnormal brain MRI findings were associated with the presence of neurologic (P = .003) and craniofacial (P = .034) disease. A total of 44 (32.1%) patients underwent genetic testing, of whom 29 (65.9%) had pathogenic results. More than 60% of the children with CCO who underwent MRI had abnormal brain and orbit findings that were correlated with significant neurologic disease. Furthermore, almost two-thirds of patients with CCO who underwent genetic testing had pathogenic results. These data demonstrate the value of systemic workup in children with CCO, and highlight the role of ophthalmologists in facilitating the diagnosis of systemic comorbidities associated with CCO.

Prevalence and Risk Factors for Tube-Feeding at Discharge in Infants following Early Congenital Heart Disease Surgery: A Single-Center Cohort Study.

Oral feeding difficulty is common in infants after congenital heart disease (CHD) surgical repair and is associated with prolonged hospital stay and increased risk for tube-feeding at discharge (TF). The current understanding of the enteropathogenesis of oral feeding difficulty in infants requiring CHD surgery is limited. To determine the prevalence and risk factors for TF following CHD surgery in early infancy. This was a 6-year single-center retrospective cohort study (2016-2021) of infants under 6 months who had CHD surgery. Infants required TF were compared with infants who reached independent oral feeding (IOF). Of the final sample of 128 infants, 24 (18.8%) infants required TF at discharge. The risk factors for TF in univariate analysis include low birth weight, low 5-minute Apgar score, admitted at birth, risk adjustment in congenital heart surgery categories IV to VI, presence of genetic diagnosis, use of Prostin, higher pre- and postsurgery respiratory support, lower weight at surgery, lower presurgery oral feeding, higher presurgery milk calory, delayed postsurgery enteral and oral feeding, higher pre- and postsurgery gastroesophageal reflux disease (GERD), need for swallow study, abnormal brain magnetic resonance imaging (p < 0.05). In the multivariate analysis, only admitted at birth, higher presurgery milk calories, and GERD were significant risk factors for TF. TF had significantly longer hospital stay (72 vs. 17 days) and lower weight gain at discharge (z-score: -3.59 vs. -1.94) compared with IOF (p < 0.05). The prevalence of TF at discharge in our study is comparable to previous studies. Infants with CHD admitted at birth, received higher presurgery milk calories, and clinical GERD are significant risk factors for TF. Mitigating the effects of identified risk factors for TF will have significant impact on the quality of life for these infants and their families and may reduce health care cost. · Oral feeding difficulty in infants after congenital heart disease surgical repair is common.. · Such infants require prolonged hospital stay and higher risk for tube-feeding at discharge.. · Identifying modifiable risk factors associated with tube-feeding can enhance clinical outcomes..

THU192 Prevalence Of Brain Abnormalities In Children With Central Precocious Puberty

Abstract Disclosure: A.A. Bastos: None. A.P. Machado Canton: None. L.B. Macena: None. L.F. Pedrosa: None. B.B. Mendonca: None. V.N. Brito: None. A. Latronico: None. Introduction: Brain magnetic resonance imaging (MRI) is the main tool used to investigate the etiology of central precocious puberty (CPP) in children. A systematic review study showed an overall prevalence of 9% of brain lesions in girls with CPP. Aim: To assess the frequency brain lesions in children with CPP. Patients and Methods: In this retrospective study, we recruited data of 163 brain MRI of children with CPP (140 girls,86%; and 23 boys, 14%) followed in a pediatric endocrinology unit from 1990 to 2022. Brain lesions were classified as congenital or acquired, and causative of CPP or incidental. Results: In girls, normal brain MRI was found in 82/140 (59%). Abnormal brain MRI was identified in the remaining 58 girls (41%), with 26 presenting congenital lesions causative of CPP (11 hypothalamic hamartoma, 7 hydrocephalus, 3 optic pathway gliomas, 2 corpus callosum agenesia, 1 pinealoma, 1 tuberous sclerosis, 1 choroid plexus papilloma), and 32 with incidental findings (microadenomas, pituitary stalk deviation, pituitary hyperplasia, rathke cleft cyst, hippocampal alterations). The overall frequency of incidental findings was 20.8%. In addition, the frequency of brain MRI pathological abnormalities in girls older than 6 years without neuro ophthalmological symptoms was 12%(n=7). In boys, normal brain MRI was found in 6/23 (26%). Abnormal brain MRI was identified in the remaining 17 boys, with 14 presenting congenital lesions causative of CPP (9 hypothalamic hamartoma, 4 hydrocephalus, 1 pineal teratoma) and 1 with acquired lesions (1 pilocytic astrocytoma). Incidental findings were detected in only 2 brain MRI (1 pineal cyst and 1 microadenoma). Incidentalomes were more frequent in girls and lesions that can be associated with CPP were more common in boys. Conclusion: The frequency of pathological brain lesions was higher in CPP boys. Hypothalamic hamartoma was the most frequent congenital lesion identified in both sexes. Based on the frequency of pathological brain alterations in girls older than 6 years we recommend to perform brain MRI in all CPP girls. Presentation: Thursday, June 15, 2023

THU177 Brain Magnetic Resonance Imaging Abnormalities And Effect On Growth Response In Children With Growth Hormone Deficiency

Abstract Disclosure: J. Choe: None. J. Lee: None. J. Kim: None. Purpose: There have been several studies on the association between structural abnormalities of the pituitary gland and its function. However, no studies have yet been conducted on children with idiopathic growth hormone deficiency (GHD) in Korea. We investigated clinical and laboratory findings of Korean children of idiopathic GHD by the presence or absence of pathologies in the pituitary gland. Material/Methods: A total of 479 patients were included from the LG growth study database. Participants had idiopathic GHD with available pituitary magnetic resonance imaging (MRI) and were treated with GH for at least 1 year between Feb, 2001 and Feb, 2020. Clinical characteristics were retrieved from the LG growth study database. Patients were divided into 3 groups according to pituitary MRI findings: (1) pathological findings in the pituitary gland; (2) pathological findings outside the pituitary gland; (3) without pathological findings with MRI. Results: Of the 479 patients, 297 (62.0%) were male and 198 (83.5%) were prepubertal. Their mean age was 7.56±2.95 years (2-16 years) and mean age of GH treatment was 7.56±2.96 years. Pituitary MR images of 354 (73.9%) patients were normal. Of the patients with detected pathologies (26.1%), 77 (61.6%) had pituitary hypoplasia, 15 (12.0%) had Rathke’s cleft cyst, 6 (0.05%) had partial empty sella, 6 (0.05%) had an arachnoid cyst, 3 (0.02%) had ectopic neurohypophysis, and 3 (0.02%) had a pineal cyst. There was no statistically significant difference in the height velocity after one year of GH treatment between groups with or without pituitary pathology (height SDS 0.71±0.34 with pituitary pathology and 0.66±0.35 with pituitary pathology; p=0.09). Conclusions: Among Korean children with GHD, approximately one-quarter of patients had abnormal pituitary MRI findings. There were no significant differences in predicting GH treatment response regardless of pituitary MRI abnormalities. Further long-term studies are needed. Presentation: Thursday, June 15, 2023

MAST1-related mega-corpus-callosum syndrome with central hypogonadism

ObjectiveHeterozygous variations in microtubule-associated serine/threonine kinase 1 gene (MAST1) were recently described in the mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations (MCCCHCM, MIM 618273), revealing the importance of the MAST genes family in global brain development.To date, patients with MAST1 gene mutations were mostly young children with central nervous system involvement, impaired motor function, speech delay, and brain magnetic resonance imaging (MRI) abnormalities. Here, we report the clinical presentation of an adult patient with a rare and de novo MAST1 mutation with central hypogonadism that could extend this phenotype. MethodsA panel of 333 genes involved in epilepsy or cortical development was sequenced in the described patient. Routine biochemical analyses were performed, and hormonal status was investigated. ResultWe report a 22-year-old man with a de novo, heterozygous missense variant in MAST1 (Chr19(GRCh37):g.12975903G > A, NP_055790.1:p.Gly517Ser). He presented with an epileptic encephalopathy associated with cerebral malformations, short stature, hypogonadotropic hypogonadism, and secondary osteopenia. ConclusionThis is the first patient with MAST1 gene mutation described with central hypogonadism, which may be associated with the phenotype of MCCCHCM syndrome.

Evaluation of brain development and damage using magnetic resonance imaging of congenital diaphragmatic hernia survivors: An analysis using the global brain abnormality score

The short-term prognosis of central nervous system in congenital diaphragmatic hernia (CDH) survivors has been determined by magnetic resonance imaging (MRI), but its relationship with acute management is unclear. We aimed to investigate the association between the intubation period and the Global Brain Abnormality Score (GBAS) in CDH survivors using brain MRI. Fifty-seven patients with CDH who were hospitalized at a single NICU between January 2004 and December 2019 were retrospectively reviewed. After excluding 5 patients who died shortly after birth and two who could not be weaned from the ventilator, the acute management of the 50 remaining patients was investigated. We also investigated the relationship between the GBAS and intubation period in 25 patients who underwent brain MRI at discharge. The long-intubation group (intubation ≥12 days) had lower Apgar scores and fetal lung-thoracic ratios, and longer time to radical surgery, and parenteral nutrition and tube feeding periods. Nitric oxide inhalation, liver prolapse, patch closure, and extracorporeal membrane oxygenation were independent risk factors for long-intubation. Eighty-four percent of CDH survivors had some imaging abnormalities, including developmental and signaling abnormalities. In the long-intubation group, the body of the corpus callosum was thin and the cerebral hemispheric space was widened, and GBAS deterioration was significantly related to the intubation period. Brain MRI abnormalities were found in 84% of CDH survivors. Prolonged intubation is associated with worsening of the GBAS. Thus, the duration of intubation may be a surrogate outcome for the neurological prognosis of CDH survivors.

Brain Magnetic Resonance Imaging Abnormalities in Acute Flaccid Myelitis

BackgroundAcute flaccid myelitis (AFM) presents with acute onset of flaccid paralysis with involvement of the gray matter on magnetic resonance imaging (MRI) of the spinal cord. Studies have reported brain MRI abnormalities, but the characteristics have not been fully defined. In this multicenter study, we assessed the acute features and evolution of brain MRI abnormalities in AFM. MethodsWe reviewed brain MRIs of patients with AFM who presented to four referral hospitals between 2012 and 2018. Cases met established criteria for AFM. We analyzed the initial and follow-up brain MRIs. Areas were divided into supratentorial, infratentorial, and subdivisions within those regions. ResultsA total of 66 patients were included. Brain MRI abnormalities were present in 34 (52%). Infratentorial abnormalities were more common, occurring in 33 (97%) cases with the dorsal pons being the most frequently affected area (88%). Abnormalities were also present in the medulla (74%), cerebellum (41%), and midbrain (38%). Nine subjects (26%) exhibited both supratentorial and infratentorial abnormalities, whereas isolated supratentorial changes were present in only one (3%). Contrast-enhancing abnormalities were encountered in 9% of cases and meningeal involvement in 6%. On follow-up, most abnormalities, 20 of 24 (83%), were stable, improving, or had resolved. ConclusionsBrain MRI abnormalities occur in about half of the cases of AFM and commonly resolve with time. Dorsal pontine involvement is a characteristic MRI feature, whereas isolated supratentorial abnormalities are rare. Clinicians should consider that brain imaging abnormalities do not exclude a diagnosis of AFM in patients with typical presentations.