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Frontiers in Pediatrics 2024Tubulin plays an essential role in cortical development, and encodes a major neuronal -tubulin. Neonatal mutations in are associated with severe brain malformations,...
Tubulin plays an essential role in cortical development, and encodes a major neuronal -tubulin. Neonatal mutations in are associated with severe brain malformations, and approximately 70% of patients with reported cases of mutations exhibit lissencephaly. We report the case of a 1-year-old boy with the nascent mutation c.1204C >T, p.Arg402Cys, resulting in lissencephaly, developmental delay, and seizures, with a brain MRI showing normal cortical formation in the bilateral frontal lobes, smooth temporo-parieto-occipital gyri and shallow sulcus. This case has not been described in any previous report; thus, the present case provides new insights into the broad disease phenotype and diagnosis associated with mutations. In addition, we have summarized the gene mutation sites, neuroradiological findings, and clinical details of cases previously described in the literature and discussed the differences that exist between individual cases of mutations through a longitudinal comparative analysis of similar cases. The complexity of the disease is revealed, and the importance of confirming the genetic diagnosis from the beginning of the disease is emphasized, which can effectively shorten the diagnostic delay and help clinicians provide genetic and therapeutic counseling.
PubMed: 38813542
DOI: 10.3389/fped.2024.1367305 -
Frontiers in Neurology 2024Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with...
BACKGROUND
Primary central nervous system post-transplant lymphoproliferative disorder (PCNS-PTLD) is a rare condition, posing diagnostic and treatment challenges, with histological biopsy essential for diagnosis. Standardized treatment protocols are lacking. This disease requires urgent attention due to the increasing number of organ transplant surgeries and the use of immunosuppressive agents.
METHODS
From 2020 to 2023, our center diagnosed five patients with PCNS-PTLD. We reviewed their clinical records and conducted a comprehensive analysis of 22 literatures on PCNS-PTLD cases following renal transplantation or allogeneic hematopoietic stem cell transplantation (HSCT).
RESULTS
Four patients had previously received a kidney transplant, one had undergone allogeneic HSCT. The median time from the last transplant surgery to the diagnosis of PCNS-PTLD differs between kidney transplant (21.5 years) and allogeneic HSCT (9 months). Common symptoms included motor weakness ( = 4), headache ( = 2), confusion ( = 2), and nausea ( = 2), with ring-enhancing ( = 5), typically solitary ( = 3) and supratentorial ( = 3) lesions on imaging. Diagnosis involved robot-assisted stereotactic brain biopsy ( = 4) or craniotomy ( = 1), all showing Epstein-Barr virus and CD20 positivity. Most cases ( = 4) were monomorphic diffuse large B-cell lymphoma. Treatment included rituximab ( = 3), surgical resection ( = 2), zanubrutinib ( = 1), whole-brain radiation ( = 1), and methotrexate ( = 1). At the last follow-up, the median duration of follow-up for all patients was 19 months. During this time, 3 patients had died and 2 patients were still alive.
CONCLUSION
In patients with a history of kidney transplantation or allogeneic HSCT who are on long-term immunosuppressive therapy, any neurological symptoms, particularly the presence of supratentorial ring-enhancing masses in the brain on imaging, whether solitary or multiple, should raise high suspicion for this disease, warranting a timely brain biopsy. Additionally, we found that besides reducing immunosuppressants, zanubrutinib may be a potential, safe, and effective treatment for this condition. Moreover, post-surgical administration of rituximab in conjunction with whole-brain radiotherapy also appears to be a potentially safe and effective approach.
PubMed: 38813246
DOI: 10.3389/fneur.2024.1392691 -
Frontiers in Cellular Neuroscience 2024Neural stem cells (NSCs) are essential for both embryonic development and adult neurogenesis, and their dysregulation causes a number of neurodevelopmental disorders,...
INTRODUCTION
Neural stem cells (NSCs) are essential for both embryonic development and adult neurogenesis, and their dysregulation causes a number of neurodevelopmental disorders, such as epilepsy and autism spectrum disorders. NSC proliferation and differentiation in the developing brain is a complex process controlled by various intrinsic and extrinsic stimuli. The mammalian target of rapamycin (mTOR) regulates proliferation and differentiation, among other cellular functions, and disruption in the mTOR pathway can lead to severe nervous system development deficits. In this study, we investigated the effect of inhibition of the mTOR pathway by rapamycin (Rapa) on NSC proliferation and differentiation.
METHODS
The NSC cultures were treated with Rapa for 1, 2, 6, 24, and 48 h. The effect on cellular functions was assessed by immunofluorescence staining, western blotting, and proliferation/metabolic assays.
RESULTS
mTOR inhibition suppressed NSC proliferation/metabolic activity as well as S-Phase entry by as early as 1 h of Rapa treatment and this effect persisted up to 48 h of Rapa treatment. In a separate experiment, NSCs were differentiated for 2 weeks after treatment with Rapa for 24 or 48 h. Regarding the effect on neuronal and glial differentiation (2 weeks post-treatment), this was suppressed in NSCs deficient in mTOR signaling, as evidenced by downregulated expression of NeuN, MAP2, and GFAP. We assume that the prolonged effect of mTOR inhibition is realized due to the effect on cytoskeletal proteins.
DISCUSSION
Here, we demonstrate for the first time that the mTOR pathway not only regulates NSC proliferation but also plays an important role in NSC differentiation into both neuronal and glial lineages.
PubMed: 38812794
DOI: 10.3389/fncel.2024.1298182 -
Frontiers in Neurology 2024
PubMed: 38803645
DOI: 10.3389/fneur.2024.1394248 -
Frontiers in Neuroscience 2024Alopecia intellectual disability syndromes 4 (APMR4) caused by Lanosterol synthase () gene variants is a very rare autosomal recessive neuroectodermal syndrome. It is...
Alopecia intellectual disability syndromes 4 (APMR4) caused by Lanosterol synthase () gene variants is a very rare autosomal recessive neuroectodermal syndrome. It is characterized by congenital alopecia and variable degrees of intellectual disability (ID), frequently associated with developmental delay (DD) and epilepsy. Currently, only three studies regarding -related APMR4 have been reported, the pathogenesis of APMR4 is poorly understood. We studied one patient with -related APMR4 who presented with severe intellectual disability, alopecia, early-onset epilepsy and developmental delay. She is absence of hair on the eyebrows, eyelashes, and scalp. Two novel variants (c.401 T > G and c.369C > G) were detected with whole-exome sequencing (WES). Analysis via WB experiment indicated that c.369 > G reduced the protein expression level of . Analysis of protein stability prediction showed a destabilizing for caused by the variant c.401 T > G. This study is the first study in Asia to date. These findings expanded the variantal spectrum of -related APMR4 and revealed the potential pathogenic mechanism of gene variants.
PubMed: 38800572
DOI: 10.3389/fnins.2024.1301865 -
Frontiers in Psychiatry 2024Epileptologists and psychiatrists have long observed a correlation between epilepsy and personality disorders (PDs) in their clinical practice. We conducted a... (Review)
Review
Epileptologists and psychiatrists have long observed a correlation between epilepsy and personality disorders (PDs) in their clinical practice. We conducted a comprehensive PubMed search looking for evidence on PDs in people with epilepsy (PwE). Out of over 600 results obtained without applying any time restriction, we selected only relevant studies (both analytical and descriptive) limited to English, Italian, French and Spanish languages, with a specific focus on PDs, rather than traits or symptoms, thus narrowing our search down to 23 eligible studies. PDs have been investigated in focal epilepsy (predominantly temporal lobe epilepsy - TLE), juvenile myoclonic epilepsy (JME) and psychogenic non-epileptic seizures (PNES), with heterogeneous methodology. Prevalence rates of PDs in focal epilepsy ranged from 18 to 42% in surgical candidates or post-surgical individuals, with Cluster C personality disorders or related traits and symptoms being most common. In JME, prevalence rates ranged from 8 to 23%, with no strong correlation with any specific PDs subtype. In PNES, prevalence rates ranged from 30 to 60%, with a notable association with Cluster B personality disorders, particularly borderline personality disorder. The presence of a PD in PwE, irrespective of subtype, complicates treatment management. However, substantial gaps of knowledge exist concerning the neurobiological substrate, effects of antiseizure medications and epilepsy surgery on concomitant PDs, all of which are indeed potential paths for future research.
PubMed: 38800062
DOI: 10.3389/fpsyt.2024.1404856 -
Frontiers in Psychiatry 2024Delivering cognitive behavioral therapy for insomnia over the internet bears the advantage of accessibility and uptake to many patients suffering from chronic insomnia....
INTRODUCTION
Delivering cognitive behavioral therapy for insomnia over the internet bears the advantage of accessibility and uptake to many patients suffering from chronic insomnia. In the current study, we aimed to investigate the effectiveness of internet-based cognitive behavioral therapy for insomnia (iCBT-I) in routine care.
MATERIALS AND METHODS
We conducted a two-arm non-blinded randomized controlled trial with care as usual (CAU) as a control condition. Participants were recruited in a specialized outpatient sleep medicine department. Both arms had access to other healthcare resources, and the intervention group had access to the iCBT-I program for 2 months. The primary outcome was insomnia severity, measured by the Insomnia Severity Index (ISI). Secondary outcomes were fatigue severity, daytime sleepiness, affective symptoms, dysfunctional beliefs and attitudes about sleep, sleep locus of control, sleep hygiene, sleep efficiency (SE), sleep onset latency, wake time after sleep onset (WASO), and total sleep time (TST). Linear mixed models for repeated measures were used to analyze the longitudinal data at baseline, post-treatment, and after 3 months of follow-up. The trial was registered at www.clinicaltrials.gov (NCT04300218 21.04.2020).
RESULTS
The results showed a significant time*group interaction effect ( = 0.001) at post-treatment with between-group effect size ( = 0.51), indicating that the ISI decreased by a score of 3.8-fold in the iCBT-I group than in the CAU group. There was no significant difference in ISI between groups at follow-up. Regarding secondary outcomes, dysfunctional beliefs about sleep, SE, and WASO decreased significantly during treatment in the intervention group with between-group effect sizes = 0.35, = 0.51, and = 0.47, respectively. At the follow-up, between-group effects on DBAS and SE remained significant: = 0.36 and = 0.63, respectively. For TST, we observed a significant time*group effect of = 0.38 only after follow-up.
CONCLUSION
Our findings suggest that iCBT-I has a significant effect on insomnia severity at post-treatment compared to CAU. iCBT-I further improved dysfunctional beliefs about sleep and improved subjective sleep characteristics, such as SE, WASO, and TST during 3 months after treatment.
CLINICAL TRIAL REGISTRATION
www.clinicaltrials.gov, identifier (NCT04300218).
PubMed: 38800061
DOI: 10.3389/fpsyt.2024.1301489 -
Frontiers in Neurology 2024This study aimed to validate a sleep staging algorithm using in-hospital video-electroencephalogram (EEG) in children without epilepsy, with well-controlled epilepsy...
OBJECTIVES
This study aimed to validate a sleep staging algorithm using in-hospital video-electroencephalogram (EEG) in children without epilepsy, with well-controlled epilepsy (WCE), and with drug-resistant epilepsy (DRE).
METHODS
Overnight video-EEG, along with electrooculogram (EOG) and chin electromyogram (EMG), was recorded in children between 4 and 18 years of age. Classical sleep staging was performed manually as a ground truth. An end-to-end hierarchical recurrent neural network for sequence-to-sequence automatic sleep staging (SeqSleepNet) was used to perform automated sleep staging using three channels: C4-A1, EOG, and chin EMG.
RESULTS
In 176 children sleep stages were manually scored: 47 children without epilepsy, 74 with WCE, and 55 with DRE. The 5-class sleep staging accuracy of the automatic sleep staging algorithm was 84.7% for the children without epilepsy, 83.5% for those with WCE, and 80.8% for those with DRE (Kappa of 0.79, 0.77, and 0.73 respectively). Performance per sleep stage was assessed with an F1 score of 0.91 for wake, 0.50 for N1, 0.83 for N2, 0.84 for N3, and 0.86 for rapid eye movement (REM) sleep.
CONCLUSION
We concluded that the tested algorithm has a high accuracy in children without epilepsy and with WCE. Performance in children with DRE was acceptable, but significantly lower, which could be explained by a tendency of more time spent in N1, and by abundant interictal epileptiform discharges and intellectual disability leading to less recognizable sleep stages. REM sleep time, however, significantly affected in children with DRE, can be detected reliably by the algorithm.: ClinicalTrials.gov, identifier NCT04584385.
PubMed: 38798709
DOI: 10.3389/fneur.2024.1390465 -
Epilepsia Open May 2024To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE). (Review)
Review
OBJECTIVE
To evaluate the prevalence of and risk factors for attention-deficit/hyperactivity disorder (ADHD) in children with epilepsy (CWE).
METHODS
We conducted a systematic search in PubMed and Embase for the meta-analysis. The pooled prevalence of ADHD was calculated using a random-effects model; subgroup analyses were performed to explore heterogeneity. We collected raw data from articles reporting potential risk factors, which were included in the subsequent risk factor analysis.
RESULTS
Forty-six articles met the inclusion criteria for the meta-analysis, which showed a pooled ADHD prevalence of 30.7% in CWE, with a predominance of the inattentive subtype of ADHD; the heterogeneity of prevalence was related to population source/study setting (clinic based, community based, or database based) and method of ADHD diagnosis (with or without clinical review). Risk factors for ADHD in epilepsy included younger age, intellectual/developmental disabilities, a family history of epilepsy, earlier epilepsy onset, absence epilepsy, more frequent seizures, and polytherapy; In contrast, risk factors such as sex, generalized epilepsy or seizures, epilepsy etiology, and electroencephalogram abnormalities were not significantly associated with the occurrence of ADHD.
SIGNIFICANCE
The prevalence of ADHD in CWE is high and several potential risk factors are associated with it. This study contributes to a better understanding of ADHD in epilepsy for screening and treatment.
PLAIN LANGUAGE SUMMARY
This systematic review summarizes the prevalence of attention-deficit/hyperactivity disorder (ADHD) occurring in children with epilepsy and analyses the risk factors for comorbid ADHD in epilepsy. By reviewing 46 articles, we concluded that the overall prevalence of ADHD in children with epilepsy was 30.7% and that intellectual/developmental disabilities were the most significant risk factor for combined ADHD in children with epilepsy. This study provides a wealth of information on comorbid ADHD in epilepsy, which will help clinicians identify and treat potential ADHD in children with epilepsy in a timely manner.
PubMed: 38798030
DOI: 10.1002/epi4.12939 -
Frontiers in Neuroscience 2024Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural...
OBJECTIVE
Mesial temporal lobe epilepsy (mTLE) is a complex neurological disorder that has been recognized as a widespread global network disorder. The group-level structural covariance network (SCN) could reveal the structural connectivity disruption of the mTLE but could not reflect the heterogeneity at the individual level.
METHODS
This study adopted a recently proposed individual structural covariance network (IDSCN) method to clarify the alternated structural covariance connection mode in mTLE and to associate IDSCN features with the clinical manifestations and regional brain atrophy.
RESULTS
We found significant IDSCN abnormalities in the ipsilesional hippocampus, ipsilesional precentral gyrus, bilateral caudate, and putamen in mTLE patients than in healthy controls. Moreover, the IDSCNs of these areas were positively correlated with the gray matter atrophy rate. Finally, we identified several connectivities with weak associations with disease duration, frequency, and surgery outcome.
SIGNIFICANCE
Our research highlights the role of hippo-thalamic-basal-cortical circuits in the pathophysiologic process of disrupted whole-brain morphological covariance networks in mTLE, and builds a bridge between brain-wide covariance network changes and regional brain atrophy.
PubMed: 38784092
DOI: 10.3389/fnins.2024.1381385