Corpus Callosum Abnormalities Research Articles

Concordance of Prenatal Ultrasonography and Magnetic Resonance Imaging in the Classification of Corpus Callosum Dysplasia

Background: Prenatal ultrasound has always been difficult to classify fetal corpus callosum abnormalities. This paper aims to evaluate the added value of fetal magnetic resonance imaging (MRI) to ultrasound in detecting fetal corpus callosum anomalies and the consistency of the classification of prenatal ultrasound and magnetic resonance imaging for corpus callosum anomalies. Methods: A retrospective analysis was performed of fetuses with abnormal cavum septi pellucidi who had ultrasonography and MRI in utero in Sichuan Maternal and Child Health Hospital and Wenjiang District Maternal in China and Child Health Hospital from January 2018 to December 2023. Fetal corpus callosum anomalies are classified according to the severity of the findings. The classification results of MRI were used as the diagnostic criteria. The findings detected on ultrasound (US) were compared to those detected on MRI. and the receiver operating characteristic (ROC) curve was used to analyze the sensitivity and specificity of prenatal ultrasound in diagnosing corpus callosum anomalies. The Kappa test was used to analyze the consistency of prenatal ultrasound and MRI in the classification of corpus callosum anomalies. Results: Of the 203 cases of fetuses with abnormal cavum septi pellucidi, 143 cases (70.4%) were normal, 34 cases (16.7%) had complete agenesis of the corpus callosum, and 18 cases (8.9%) had partial agenesis of the corpus callosum. Eight cases (3.9%) had dysplasia of the corpus callosum. The area under the ROC curve of prenatal ultrasound for the diagnosis of corpus callosum anomalies was 0.840 (95% confidence interval (CI) 0.782–0.888), the sensitivity was 75.00%, and the specificity was 93.01%, The positive likelihood ratio was 10.7 and the negative likelihood ratio was 0.3. Prenatal ultrasonography and MRI had moderate concordance in the classification of corpus callosum anomalies (Kappa = 0.673, p < 0.001). The concordance was good in diagnosing complete agenesis of the corpus callosum (Kappa = 0.862, p < 0.001), while the concordance was moderate in diagnosing partial agenesis of the corpus callosum (Kappa = 0.643, p < 0.001). Conclusions: Prenatal ultrasonography is accurate and effective in the diagnosis of corpus callosum anomalies. Magnetic resonance imaging can provide more information in the classification of corpus callosum anomalies and the diagnosis of neurologic complications. The MRI should be combined with ultrasonographic transverse, midsagittal, and coronal views to evaluate the classification of corpus callosum anomalies.

Bi-allelic variants in WDR47 cause a complex neurodevelopmental syndrome

Brain development requires the coordinated growth of structures and cues that are essential for forming neural circuits and cognitive functions. The corpus callosum, the largest interhemispheric connection, is formed by the axons of callosal projection neurons through a series of tightly regulated cellular events, including neuronal specification, migration, axon extension and branching. Defects in any of those steps can lead to a range of disorders known as syndromic corpus callosum dysgenesis (CCD). We report five unrelated families carrying bi-allelic variants in WDR47 presenting with CCD together with other neuroanatomical phenotypes such as microcephaly and enlarged ventricles. Using in vitro and in vivo mouse models and complementation assays, we show that WDR47 is required for survival of callosal neurons by contributing to the maintenance of mitochondrial and microtubule homeostasis. We further propose that severity of the CCD phenotype is determined by the degree of the loss of function caused by the human variants. Taken together, we identify WDR47 as a causative gene of a new neurodevelopmental syndrome characterized by corpus callosum abnormalities and other neuroanatomical malformations.

Interhypothalamic adhesions: prevalence, structure, and location-based classification map in pediatric patients undergoing MRI.

Interhypothalamic adhesions (IHAs) have been reported only in the pediatric population, with unknown prevalence and histological composition. We aim to demonstrate their prevalence, assess their persistence through longitudinal imaging, classify IHAs by anatomical distribution, explore their structure, and report associated pathologies. A retrospective review was conducted on consecutive pediatric brain MRI studies obtained between January 2012, and December 2013. The presence of an IHA was only confirmed when observed on at least two planes. For each IHA, cross-sectional area was calculated, and signal intensities were measured at the center on sagittal T2WIs. Signal intensities were also measured in both cerebral white matter and gray matter for normalization and comparison. Patient demographics and clinical information were collected from electronic charts. Out of 1550 patients (0-17.9 years), 33 (19 males, 14 females) had an IHA, resulting in a 2.13% prevalence. Follow-up images were available for 19 IHA-positive patients, and IHAs were again seen in 92% of the follow-up scans (71/77). Normalized IHA signal highly correlated with normalized gray matter signal (r = 0.83, P < 0.001), but not with normalized white matter signal (r = -0.16, p = 0.494). Common co-occurring pathologies included hydrocephalus (n = 9), prematurity (n = 8), and corpus callosum abnormalities (n = 7). All type 3 IHAs (3/3) were accompanied by pituitary pathologies. IHAs have a prevalence of 2.13% in our cohort, and the majority persist in longitudinal studies. They showed gray matter signal intensity and Type 3 IHAs exclusively accompanied pituitary abnormalities.

The shape of the corpus callosum is different in bipolar disorder.

Bipolar disorder (BD) is a recurrent chronic disorder characterised by fluctuations in mood and energy disposition. Diseases could lead to degenerative alterations in brain structures such as corpus callosum (CC). Studies demonstrated that abnormalities in CC are associated with BD symptoms. The present study aims to analyse the CC of the patients with statistical shape analysis (SSA) and compare the findings with healthy controls. Forty-one BD patients and 41 healthy individuals in similar age groups, which included 23 female and 18 male subjects, participated in the study. CC was marked with landmarks on the mid-sagittal images of each individual. The mean 'Procrustes' point was calculated, and shape deformations were analysed with thin-plate spline analysis. Significant differences were observed in the shape of CC between the two groups, where maximum CC deformation was observed in posterior region marks in BD patients. There was no significant difference between the CC area of the BD patients and controls. CC analysis conducted with SSA revealed significant differences between patients and healthy controls. The study findings emphasised the abnormal distribution of white matter in CC and the variable subregional nature of CC in BD patients. This study may enable the development of more targeted and effective treatment strategies by taking into account biological factors and understanding the differences in the brain regions of individuals with BD.

Basic helix-loop-helix transcription factor BHLHE22 monoallelic and biallelic variants cause a neurodevelopmental disorder with agenesis of the corpus callosum, intellectual disability, tone and movement abnormalities.

BHLHE22 encodes a Class II basic helix-loop-helix transcription factor (bHLH). It is expressed exclusively in the retina and central nervous system (CNS), and functions as an important regulator of retinogenesis and neuronal differentiation. Mice lacking bhlhe22 show nearly complete loss of three brain comminsure, including the corpus callosum. Here we report eleven individuals from nine unrelated families with BHLHE22 variants, with a neurodevelopmental disorder presenting with absent or limited speech, severely impaired motor abilities, intellectual disability (ID), involuntary movements, autistic traits with stereotypies, abnormal muscle tone. The majority of individuals have partial or complete agenesis of the corpus callosum (ACC). Additional symptoms comprised epilepsy, variable dysmorphic features, and eye anomalies. One additional individual had spastic paraplegia without delayed development and ACC, expanding the phenotype to milder and later onset forms. Four individuals carry de novo missense variants within the highly conserved helix-loop-helix domain while seven individuals from five unrelated families carry a recurrent homozygous frameshift variant, p.(Gly74Alafs*18). Our findings implicate BHLHE22 variants in causing a previously unidentified autosomal dominant and recessive neurodevelopmental disorder associated with ACC, severe motor, language, and cognitive delays, abnormal tone, and involuntary movements. To our knowledge, this is the first report of Class II bHLH variants in humans shown to significantly disrupt brain development, cognition, and movement.

Fetal MRI findings, etiology, and outcome in prenatally diagnosed schizencephaly.

Schizencephaly is a rare brain anomaly which is increasingly detected in utero. There are limited data on the etiology and outcomes in fetal schizencephaly to guide workup and counselling. We aim to determine the associated imaging findings, etiology, and outcomes in schizencephaly detected in utero. This retrospective cohort study included 22 fetuses with a total of 34 schizencephaly defects identified by keyword search of fetal MRI reports from 1996-2022 followed by image review. Follow-up fetal and postnatal imaging, when available, were reviewed. Data on demographics, etiology, and outcomes were extracted from the electronic medical record. The schizencephaly defect was open in 28/34, most common in the MCA territory (23/34), and commonly involved the frontal (16/34) lobe. Additional intracranial abnormalities were seen in all fetuses including other cortical malformations (CM, 13/22), abnormal posterior fossa (12/22), abnormal corpus callosum (10/20), and intraparenchymal hemorrhage (9/22).The cause of schizencephaly was classified as secondary (as evidenced by intraparenchymal hemorrhage at schizencephaly, monochorionic twin gestation, infection, or maternal/placental risk factor) in 64% (14/22), potentially genetic in 9% (2/22), and unknown in 27% (6/22). Among those liveborn (n=8), the following outcomes were observed: postnatal death (1/8), tube feeding (1/7), shunted hydrocephalus (1/7), epilepsy (4/7). Among those >1 year of age, cerebral palsy (4/5) and speech delay or intellectual disability (3/5) were common. CM remote from schizencephaly was associated with epilepsy (p=0.03). On postnatal imaging, open defects often involuted (8/11) and there were high rates of new/additional findings (4/6). In this cohort, fetal schizencephaly was always associated with additional intracranial abnormalities. In most cases, there was evidence that schizencephaly was likely secondary to prior injury. Imaging characteristics may provide clues regarding neurodevelopmental outcome. Postnatal imaging is crucial in assessing evolution as well as for detection of additional abnormalities. ICH = intracranial hemorrhage; CM = cortical malformation; VM = ventriculomegaly; DGN = deep grey nuclei; SP = septum pellucidum; IPH = intraparenchymal hemorrhage; CC = corpus callosum; PMG = polymicrogyria; PVNH = periventricular nodular heterotopia; TTTS = twin-twin transfusion syndrome; GA = gestational age; CP = cerebral palsy.

Reference charts for fetal corpus callosum length in the early second trimester: a prospective cross-sectional study.

This study aimed to establish normal reference ranges for fetal corpus callosum (CC) measured by prenatal ultrasonography (USG) between 16 and 25weeks of gestation in healthy fetuses. A total of 809 fetuses in the second trimester were evaluated by transabdominal USG. All measurements were obtained by a single clinician. Based on the correlation analysis, a significant positive correlation was found between gestational week and CC (r = 0.907, p < 0.001). We anticipate that the reference intervals obtained from healthy fetuses will help clinicians who are interested in neurosonography to detect CC abnormalities at an early stage.

Aberrant connectivity of the lateralized readiness system in non-syndromic congenital mirror movements

ObjectivesNon-syndromic CMM has a complex phenotype. Abnormal corpus callosum and corticospinal tract processes are suggested mechanisms of the mirror movements. To further explore behavioural and neural phenotype(s) the present study tests the hypothesis that the response readiness network comprising supplementary motor area (SMA) and connections with motor cortex (M1) functions abnormally in CMM. MethodsTwelve participants with (non-syndromic) CMM and a control group (n = 28) were tested on a probabilistic Go-NoGo task while electroencephalography (EEG) was recorded to assess possible group differences in lateralized readiness of voluntary hand movements together with measures of SMA-M1 functional connectivity. ResultsThe CMM group demonstrated delayed lateralized readiness and stronger functional connectivity between left-brain SMA-M1 regions. Connectivity strength was correlated with measures of behavioural performance but not with extent of mirroring. ConclusionsAbnormalities in brain processes upstream of movement output likely reflect neurocompensation as a result of lifelong experience with mirroring in CMM. SignificanceThese findings extend the known neural abnormalities in CMM to include brain networks upstream from those involved in motor output and raise the question of whether neurocompensatory plasticity might be involved.

Periventricular Leukomalacia: Comparison of Parenchymal Signal and Volume Changes on Brain MRI in Paediatric Cases with Healthy Peers

Background/aims: Previous MRI studies have shown white matter (WM) and gray matter (GM) of cerebrum and cerebellum, corpus callosum (CC) abnormalities in periventricular leukomalacia (PVL). But, the WM FLAIR signal ratio in MRI may provide quantitative data in the diagnosis and follow-up, as a new radiologic method. Thalamic involvement may be a biomarker for neuronal damage and disease severity. We aimed to re-investigate both WM and GM volume changes of cerebrum and cerebellum, CC surface area in PVL, and to evaluate the diagnostic accuracy of the thalamus L sign and FLAIR signal ratio. Methods: MRI scans of 30 pediatric patients with PVL and 42 healthy controls were analyzed to examine WM and GM volume changes, FLAIR signal ratio, CC surface area, and thalamus L sign. Volumetric analyses were done with the Volbrain program. Results: Decreased subcortical GM volumes were found in PVL (p0.001). Conclusions: Our results emphasise the role of MRI in the detection of PVL, the evaluation of GM changes and brain damage, and the importance of thalamus L sign and FLAIR signal ratio in the evaluation of the severity of the disease. Comprehensive studies in this direction may contribute to the development of targeted treatment strategies aimed at reducing cognitive and motor impairments in PVL.

Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.

The corpus callosum is one of the five main cerebral commissures. It is key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). The corpus callosum dys- or agenesis is a rare disease (1:4000 live births), but it can have serious mental effects. In our study, we processed the data of 64 pregnant women. They attended a prenatal diagnostic center and genetic counseling from 2005 to 2019 at the Department of Obstetrics and Gynecology at Semmelweis University. The pregnancies had the following outcomes: 52 ended in delivery, 1 in spontaneous abortion, and 11 in termination of pregnancy (TOP) cases (n = 64). The average time of detection with imaging tests was 25.24 gestational weeks. In 16 cases, prenatal magnetic resonance imaging (MRI) was performed. If the abnormality was detected before the 20th week, a genetic test was performed on an amniotic fluid sample obtained from a genetic amniocentesis. Karyotyping and cytogenetic tests were performed in 15 of the investigated cases. Karyotyping gave normal results in three cases (46,XX or XY). In one of these cases, postnatally chromosomal microarray (CMA) was later performed, which confirmed Aicardi syndrome (3q21.3-21.1 microdeletion). In one case, postnatally, the test found Wiedemann-Rautenstrauch syndrome. In other cases, it found X ring, Di George syndrome, 46,XY,del(13q)(q13q22) and 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards syndrome was diagnosed in six cases, and Patau syndrome in one case. We found that corpus callosum abnormalities are often linked to chromosomal problems. We recommend that a cytogenetic test be performed in all cases to rule out inherited diseases. Also, the long-term outcome does not just depend on the disease's severity and the associated other conditions, and hence proper follow-up and early development are also key. For this reason, close teamwork between neonatology, developmental neurology, and pediatric surgery is vital.

Abnormalities of Corpus Callosum and Other Interhemispheric Commissures

Abnormalities of Corpus Callosum and Other Interhemispheric Commissures

The Corpus Callosum in Schizoaffective Disorder: A Shape Analysis Study

Objective: The corpus callosum is the largest white matter structure in the human brain that connects the cortical regions of both hemispheres. Diseases could lead to degenerative alterations in brain structures such as the corpus callosum (CC). Studies have associated CC abnormalities with Schizoaffective Disorder (SAD) symptoms. We predicted that there may be differences in the CC, an important structure connecting the two halves of the brain, in patients with SAD. The present study aims to analyze the CC of patients with statistical shape analysis (SSA) and compare the findings with healthy controls. Methods: Thirty-nine SAD patients and 39 healthy individuals (11 females and 28 males) of similar age that included subjects participated in the study. CC landmarks were marked on the mid-sagittal images of each participant. The mean ‘Procrustes’ point was determined, and shape deformations were analyzed with thin plate spline analysis. Results: Significant differences were observed between the shapes of CC in the two groups, and maximum CC deformation was observed in the posterior regions of SAD patients. There was no significant difference between the CC area of the SAD patients and the controls. Conclusion: In the present study, the maximum deformation was observed in the posterior region (isthmus and splenium) and the rostrum of the CC. The first CC region, the rostrum (+genu), connects prefrontal and premotor regions, which are associated with cognitive information (landmarks = 1, 7, 8, 9, 13, 15, and 12). The second area, the splenium, connects temporal and occipital cortical areas. These predominantly have auditory, peripheral, and central visual stimulation functions (landmarks = 5, 3, and 4). The current study could assist future studies on the etiology, diagnosis, and treatment of SAD.

Prenatal ultrasound reassessment of the corpus callosum based on cortical connectivity information

IntroductionRoutine prenatal ultrasound assessment of the corpus callosum (CC) does not reflect information on fibrous connections. The primary purpose was to construct detailed reference ranges of quantitative characteristics of the foetal CC based on cortical connectivity information. Secondary goals were to examine for sex differences and assess the validity of the measurement technique for cases with CC dysplasia.Material and methodsPregnant women referred to a tertiary centre for sonographic examination were recruited to undergo a detailed foetal scan from 19 to 40 weeks. The foetal CC was divided into 5 distinct segments using the Hofer &amp; Frahm classification technique. The thickness of each segment and the overall length of the CC were measured. Additionally, a segmental evaluation was conducted on partial agenesis of the CC. The inter- and intraobserver variability were assessed by interclass correlation coefficients. Regression analysis was used to determine the association between the biological measurements and gestational age.ResultsA total of 852 foetuses (403 males and 449 females) were included in the final analysis. Intra- and interobserver reliability coefficients ranged from 0.86 to 0.98 and 0.84 to 0.97, respectively. Reference ranges were established for the thickness and length of its segments. We observed that the biometric measurements of the foetal CC showed a curvilinear increase with gestational age. There was a statistically significant sex effect for the CC. At the average gestation age 29.6 weeks, the genu, anterior midbody, posterior midbody, and isthmus of male foetuses were 0.06280 mm, 0.04435 mm, 0.01731 mm, and 0.01556 mm, respectively, thicker than those of female foetuses, whereas the splenium of the female foetus was 0.06583 mm thicker than the male foetus.ConclusionsThe study uncovers distinct patterns of thickness and length growth in the foetal CC and establishes precise reference ranges. These findings can aid in evaluating normal brain development and conducting comprehensive assessments of CC abnormalities.

Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children

BackgroundPallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population.ResultsThirty-one individuals were enrolled (17 females/14 males; age range 0.1–17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14.ConclusionsBrain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.

Corpus Callosum Abnormalities at Term-Equivalent Age Are Associated with Language Development at 2 Years’ Corrected Age in Infants Born Very Preterm

We studied the effect of microstructural abnormalities in the corpus callosum on language development in 348 infants born very prematurely. We discovered that the fractional anisotropy of the corpus callosum anterior midbody was a significant predictor of standardized language scores at 2 years, independent of clinical and social risk factors.

Fetal MRI Analysis of Corpus Callosal Abnormalities: Classification, and Associated Anomalies.

Corpus callosal abnormalities (CCA) are midline developmental brain malformations and are usually associated with a wide spectrum of other neurological and non-neurological abnormalities. The study aims to highlight the diagnostic role of fetal MRI to characterize heterogeneous corpus callosal abnormalities using the latest classification system. It also helps to identify associated anomalies, which have prognostic implications for the postnatal outcome. In this study, retrospective data from antenatal women who underwent fetal MRI between January 2014 and July 2023 at Rush University Medical Center were evaluated for CCA and classified based on structural morphology. Patients were further assessed for associated neurological and non-neurological anomalies. The most frequent class of CCA was complete agenesis (79.1%), followed by hypoplasia (12.5%), dysplasia (4.2%), and hypoplasia with dysplasia (4.2%). Among them, 17% had isolated CCA, while the majority (83%) had complex forms of CCA associated with other CNS and non-CNS anomalies. Out of the complex CCA cases, 58% were associated with other CNS anomalies, while 8% were associated with non-CNS anomalies. 17% of cases had both. The use of fetal MRI is valuable in the classification of abnormalities of the corpus callosum after the confirmation of a suspected diagnosis on prenatal ultrasound. This technique is an invaluable method for distinguishing between isolated and complex forms of CCA, especially in cases of apparent isolated CCA. The use of diffusion-weighted imaging or diffusion tensor imaging in fetal neuroimaging is expected to provide further insights into white matter abnormalities in fetuses diagnosed with CCA in the future.

Quantitative fetal MRI with diffusion tensor imaging in cases with 'short' corpus callosum.

It has been suggested previously that the presence of Probst bundles (PB) in cases with a short corpus callosum (SCC) on diffusion tensor imaging (DTI) may help to differentiate between corpus callosal (CC) dysplasia and a variant of normal CC development. The objectives of this study were to compare DTI parameters between cases of SCC vs normal CC and between cases of SCC with PB (SCC-PB+) vs SCC without PB (SCC-PB-). This was a retrospective study of patients referred to the Necker Hospital in Paris, France, for magnetic resonance imaging (MRI) evaluation of an apparently isolated SCC detected by sonography between November 2016 and December 2022 (IRB: 00011928). MRI was performed using a 1.5-Tesla Signa system. T2-weighted axial and sagittal sequences of the fetal brain were used to measure the length and thickness of the CC. 16-direction DTI axial brain sequences were performed to identify the presence of PB and to generate quantitative imaging parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) of the entire CC, genu, body and splenium. Cases in which other associated brain abnormalities were detected on MRI were excluded. Cases were matched for fetal gender and gestational age with controls in a 1:3 ratio. Control cases were normal fetuses included in the LUMIERE on the FETUS trial (NCT04142606) that underwent the same DTI evaluation of the brain. Comparisons between SCC and normal CC cases, and between SCC-PB+ and SCC-PB- cases were performed using ANOVA and adjusted for potential confounders using ANCOVA. Twenty-two SCC cases were included and compared with 66 fetuses with a normal CC. In 10/22 (45.5%) cases of SCC, PB were identified. As expected, dimensions of the CC were significantly smaller in SCC compared with normal CC cases (all P < 0.01). In SCC-PB+ vs SCC-PB- cases, FA values were significantly lower in the entire CC (median, 0.21 (range, 0.19-0.24) vs 0.24 (range, 0.22-0.28); P < 0.01), genu (median, 0.21 (range, 0.15-0.29) vs 0.24 (range, 0.17-0.29); P = 0.04), body (median, 0.21 (range, 0.18-0.23) vs 0.23 (range, 0.21-0.27); P = 0.04) and splenium (median, 0.22 (range, 0.16-0.30) vs 0.25 (range, 0.20-0.29); P = 0.03). ADC values were significantly higher in the entire CC, genu and body in SCC-PB+ vs SCC-PB- cases (all P < 0.05). In SCC-PB+ cases, all FA values were significantly lower, and ADC values in the CC body were significantly higher compared with normal CC cases (all P < 0.05). In SCC-PB- cases, there was no significant difference in FA and ADC compared with normal CC cases (all P > 0.05). Fetal DTI evaluation of the CC showed that FA values were significantly lower and ADC values tended to be significantly higher in SCC-PB+ compared with normal CC cases. This may highlight alterations of the white matter microstructure in SCC-PB+. In contrast, isolated SCC-PB- did not demonstrate significant changes in DTI parameters, strengthening the possibility that this is a normal CC variant. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage in different types of corpus callosum disorders: a comparative study in children

BackgroundThis study aimed to investigate the demographic and clinical characteristics, types of seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders.MethodsA total of 73 individuals were included in the study and divided into three groups based on the type of corpus callosum abnormality: hypoplasia (H), agenesis (A), and dysgenesis (D). Demographic data, including gender and preterm birth, as well as clinical characteristics such as seizure disorders, attention deficit hyperactivity disorder (ADHD), severe developmental delay/intellectual disability, and other brain malformations, were analyzed. The types of seizure disorders and antiepileptic drugs used were also examined.ResultsThe H group had the highest number of participants (n = 47), followed by the A group (n = 11) and the D group (n = 15). The A group had the highest percentage of males and preterm births, while the D group had the highest percentage of seizure disorders, other brain malformations, and severe developmental delay/intellectual disability. The A group also had the highest percentage of ADHD. Focal seizures were observed in all three groups, with the highest proportion in the A group. Focal impaired awareness seizures (FIAS) were present in all groups, with the highest proportion in the D group. Generalized tonic-clonic seizures (GTCS) were observed in all groups, with the highest proportion in the H group. Different types of antiepileptic drugs were used among the groups, with variations in usage rates for each drug.ConclusionThis study provided insights into the demographic and clinical characteristics, seizure disorders, and antiepileptic drug usage among individuals with different types of corpus callosum disorders. Significant differences were found between the groups, indicating the need for tailored management approaches. However, the study has limitations, including a small sample size and a cross-sectional design. Further research with larger sample sizes and longitudinal designs is warranted to validate these findings and explore the relationship between corpus callosum abnormality severity and clinical outcomes.

Novel loss-of-function variants expand ABCC9-related intellectual disability and myopathy syndrome.

Loss-of-function mutation of ABCC9, the gene encoding the SUR2 subunit of ATP sensitive-potassium (KATP) channels, was recently associated with autosomal recessive ABCC9-related intellectual disability and myopathy syndrome (AIMS). Here we identify nine additional subjects, from seven unrelated families, harbouring different homozygous loss-of-function variants in ABCC9 and presenting with a conserved range of clinical features. All variants are predicted to result in severe truncations or in-frame deletions within SUR2, leading to the generation of non-functional SUR2-dependent KATP channels. Affected individuals show psychomotor delay and intellectual disability of variable severity, microcephaly, corpus callosum and white matter abnormalities, seizures, spasticity, short stature, muscle fatigability and weakness. Heterozygous parents do not show any conserved clinical pathology but report multiple incidences of intra-uterine fetal death, which were also observed in an eighth family included in this study. In vivo studies of abcc9 loss-of-function in zebrafish revealed an exacerbated motor response to pentylenetetrazole, a pro-convulsive drug, consistent with impaired neurodevelopment associated with an increased seizure susceptibility. Our findings define an ABCC9 loss-of-function-related phenotype, expanding the genotypic and phenotypic spectrum of AIMS and reveal novel human pathologies arising from KATP channel dysfunction.

Evaluation of Cerebral and Spinal Abnormalities on Magnetic Resonance Imaging in Infants with Myelomeningocele: A Retrospective Observational Study

Introduction: Spinal dysraphism includes a diverse collection of congenital spinal abnormalities that occur due to flawed closure of the neural tube and can be classified as open or closed types. The most common form of open spinal dysraphism is Myelomeningocele (MMC), which is characterised by a bony spinal defect and a sac in the back region containing dysplastic neural tissue and cerebrospinal fluid. MMC is associated with various intracranial and spinal anomalies that can lead to neurological, intellectual, and cognitive impairments. Imaging is necessary for the diagnosis of these anomalies and for surgical management planning and follow-up. Aim: To evaluate the associated intracranial and spinal anomalies in infants with MMC who presented with low back swelling since birth. Materials and Methods: The retrospective observational study was conducted in the Department of Radiology at Gajara Raja Medical College, Gwalior, Madhya Pradesh, India, from January 2020 to December 2022. A total of 117 subjects under one year of age, clinically diagnosed with MMC, were included in the study. Brain Magnetic Resonance Imaging (MRI) images were available for 84 patients, and spine MRI images were available for 113 patients. The MRI images were evaluated for bony and spinal anomalies. Data analysis was performed using IBM’s Statistical Package for Social Sciences (SPSS) version 20.0. Results: The mean age of the study participants was 1.7±2.9 months, with 70 males and 47 females (M:F=1.5:1). The most common location of spina bifida was lumbosacral 36 (31.9%), followed by lumbar 31 (27.4%), dorsolumbar 30 (26.5%), and sacral 16 (14.2%). A low-level spinal defect was observed in 39 cases (34.5%), and a high-level spinal defect was observed in 74 cases (65.5%). The spinal anomalies detected on MRI included syringomyelia 80 (70.8%), low-lying cord 59 (52.2%), bony abnormalities 26 (23.01%), diastematomyelia 16 (14.2%), and fatty filum terminale 3 (2.7%). Among the intracranial anomalies, the most common was dilated lateral ventricles 62 (73.8%). The most common infratentorial anomaly was Chiari II malformation 58 (69.1%). Corpus Callosum (CC) abnormalities were found in 40 cases (47.6%), with complete agenesis seen in three cases (3.6%), cerebellar hypoplasia in 20 cases (23.8%), absent septum in 15 cases (17.9%), and colpocephaly in 10 cases (11.9%). Conclusion: Spinal dysraphism, such as MMC, and cerebral anomalies often co-exist and can have an impact on neurological, intellectual, and cognitive functions. Chiari II malformation, corpus callosal anomalies, ventriculomegaly, and syringomyelia are frequently associated with MMC. Therefore, imaging evaluation of both the spine and brain is necessary for surgical treatment planning and long-term follow-up in MMC.