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Brain & Development Jan 2024Some patients with ATP1A3 variant-associated polymicrogyria have recurrent transient heart failure. However, effective treatment for the transient cardiac condition...
BACKGROUND
Some patients with ATP1A3 variant-associated polymicrogyria have recurrent transient heart failure. However, effective treatment for the transient cardiac condition remains to be elucidated.
CASE REPORT
The patient started experiencing focal motor onset seizures in 12 h after birth, revealing bilateral diffuse polymicrogyria. The patient also experienced transient bradycardia (sinus bradycardia) attacks from 15 days old. Echocardiography revealed a reduced ejection fraction; however, no obvious electrocorticogram or electroencephalogram abnormalities were observed during the attacks. Initially, the attacks occurred in clusters daily. They later decreased in frequency, occurring at monthly intervals. Repeated episodes of transient bradycardia attacks and polymicrogyria indicated possible ATP1A3 gene abnormality and genetic testing revealed a novel heterozygous ATP1A3 variant (NM_152296: exon22:c.2977_2982del:p.(Glu993_Ile994del)), which was not found in the patient's parents. Cilostazol was administered at 3 months old for recurrent transient bradycardia attacks. Cilostazol significantly shortened the duration of bradycardia episodes and prolonged the interval between attacks. Cilostazol also effectively treats transient symptomatic bradycardia.
CONCLUSION
Cilostazol could be a treatment option for recurrent transient bradycardia attacks associated with ATP1A3 gene abnormalities and polymicrogyria.
Topics: Humans; Infant; Cilostazol; Bradycardia; Polymicrogyria; Heart Failure; Seizures; Sodium-Potassium-Exchanging ATPase
PubMed: 37778966
DOI: 10.1016/j.braindev.2023.09.002 -
BMJ Case Reports Sep 2023This case report presents a patient with a monochorionic twin pregnancy, development of twin-twin transfusion-syndrome (TTTS) and polymicrogyria (PMG) of one fetus. Due...
This case report presents a patient with a monochorionic twin pregnancy, development of twin-twin transfusion-syndrome (TTTS) and polymicrogyria (PMG) of one fetus. Due to TTTS grade 3, fetoscopic laser ablation was performed at gestational week 16+1. Sonographic follow-up showed a cortical malformation of the right parietal lobe in the former donor, which was identified as PMG by MRI scans. We describe the course of the pregnancy, as well as the clinical, especially neurological, development of the child over 3 years. This case report documents the power of neuroplasticity, leading to comparably good neurological outcome in an extensive, likely acquired cortical malformation. Further, it emphasises the importance of a thorough prenatal imaging characterisation of malformations of cortical development for optimal prenatal counselling of these cases.
Topics: Child; Female; Pregnancy; Humans; Polymicrogyria; Fetofetal Transfusion; Patients; Fetoscopy; Fetus
PubMed: 37739446
DOI: 10.1136/bcr-2023-255510 -
Journal of Psychiatric Practice Sep 2023Patients may present with manic symptoms in medical settings such as emergency rooms and on inpatient medical floors, leading to psychiatric consultation to try to...
Patients may present with manic symptoms in medical settings such as emergency rooms and on inpatient medical floors, leading to psychiatric consultation to try to determine the etiology of the symptoms. It is crucial to clarify whether the mania is secondary to a medical illness or whether the patient's symptoms are from a primary bipolar disorder. In this issue, we publish 2 case reports of patients presenting with manic symptoms in medical settings. The first case involves polymicrogyria in the frontal lobe of the brain as a cause of secondary mania. The second case involves a patient who was previously diagnosed with bipolar disorder and subsequently developed symptoms of Behçet's disease. In this case, it appears likely that the bipolar disorder was primary, and that the Behçet disease and the bipolar disorder may have exacerbated each other. Given the complexities involved in assessing and treating patients, especially in acute or emergency settings, it is important for primary medical and psychiatric providers to collaborate and communicate well in assuring that they obtain a thorough history of their patients' symptoms and that patients receive a comprehensive medical evaluation before psychiatric treatment is started.
Topics: Humans; Mania; Bipolar Disorder; Brain; Inpatients; Emergency Service, Hospital
PubMed: 37678372
DOI: 10.1097/PRA.0000000000000731 -
Journal of Psychiatric Practice Sep 2023Secondary mania refers to a manic episode that arises during a medical illness other than bipolar disorder or in response to a drug or medication. As the...
BACKGROUND
Secondary mania refers to a manic episode that arises during a medical illness other than bipolar disorder or in response to a drug or medication. As the psychopathological features of secondary mania resemble those of mania due to bipolar disorder, misdiagnosis is frequent.
PURPOSE AND BASIC PROCEDURES
We present the case of a 20-year-old woman who developed a manic episode with psychotic symptoms, in whom polymicrogyria, a malformation of the cortical development with abnormal electroencephalographic activity, was documented. After initiating antiepileptic management, the affective symptoms completely subsided.
MAIN FINDINGS
To date, no specific recommendations are available concerning when to perform advanced studies in patients with a manic episode; however, as our case shows, these are much needed.
PRINCIPAL CONCLUSION
Because the treatment of secondary conditions largely depends on finding the underlying cause, patients with a new-onset mania should undergo a thorough assessment for secondary causes.
Topics: Female; Humans; Young Adult; Adult; Mania; Polymicrogyria; Bipolar Disorder; Affective Symptoms; Anticonvulsants
PubMed: 37678371
DOI: 10.1097/PRA.0000000000000728 -
Ultrasound in Obstetrics & Gynecology :... Mar 2024
Topics: Humans; Female; Pregnancy; Polymicrogyria; Fetus; Prenatal Care
PubMed: 37671454
DOI: 10.1002/uog.27460 -
Neurology Nov 2023
Topics: Pregnancy; Female; Humans; Fetofetal Transfusion; Fetal Growth Retardation; Polymicrogyria; Malformations of Cortical Development; Twins, Monozygotic
PubMed: 37648524
DOI: 10.1212/WNL.0000000000207801 -
Basic & Clinical Pharmacology &... Oct 2023Adhesion G protein-coupled receptors (aGPCRs) constitute the second largest subclass of the GPCR superfamily. Although canonical GPCRs are explored pharmacologically as...
Adhesion G protein-coupled receptors (aGPCRs) constitute the second largest subclass of the GPCR superfamily. Although canonical GPCRs are explored pharmacologically as drug targets, no clinically approved drugs target the aGPCR family so far. The aGPCR GPR56/ADGRG1 stands out as an especially promising target, given its direct link to the monogenetic disease bilateral frontoparietal polymicrogyria and implications in cancers. Key to understanding GPCR pharmacology has been mapping out intracellular signalling activity. Detection of GPCR signalling in the Gα /Gα /Gα G protein pathways is feasible with second messenger detection systems. However, in the case of Gα -coupled receptors, like GPR56, signalling detection is more challenging due to the lack of direct second messenger generation. To overcome this challenge, we engineered a Gα chimera to translate Gα signalling. We show the ability of the chimeric Gα and Gα to translate basal Gα signalling of GPR56 to a Gα readout in transcription factor luciferase reporter systems and show that the established peptide ligands (P7 and P19) function to enhance this signal. We further demonstrate the ability to directly influence the generation of second messengers in inositol-3-phosphate assays. In the future, these chimeric G proteins could facilitate basic functional studies, drug screenings and deorphanization of other aGPCRs.
Topics: Signal Transduction; Receptors, G-Protein-Coupled; GTP-Binding Proteins; Peptides
PubMed: 37621135
DOI: 10.1111/bcpt.13935 -
Pediatric Neurology Oct 2023Inactivating mutations in PTEN are among the most common causes of megalencephaly. Activating mutations in other nodes of the PI3K/AKT/MTOR signaling pathway are...
BACKGROUND
Inactivating mutations in PTEN are among the most common causes of megalencephaly. Activating mutations in other nodes of the PI3K/AKT/MTOR signaling pathway are recognized as a frequent cause of cortical brain malformations. Only recently has PTEN been associated with cortical malformations, and analyses of their prognostic significance have been limited.
METHODS
Retrospective neuroimaging analysis and detailed chart review were conducted on 20 participants identified with pathogenic or likely pathogenic mutations in PTEN and a cortical brain malformation present on brain magnetic resonance imaging.
RESULTS
Neuroimaging analysis revealed four main cerebral phenotypes-hemimegalencephaly, focal cortical dysplasia, polymicrogyria (PMG), and a less severe category, termed "macrocephaly with complicated gyral pattern" (MCG). Although a high proportion of participants (90%) had neurodevelopmental findings on presentation, outcomes varied and were favorable in over half of participants. Consistent with prior work, 39% of participants had autism spectrum disorder and 19% of participants with either pure-PMG or pure-MCG phenotypes had epilepsy. Megalencephaly and systemic overgrowth were common, but other systemic features of PTEN-hamartoma tumor syndrome were absent in over one-third of participants.
CONCLUSIONS
A spectrum of cortical dysplasias is present in individuals with inactivating mutations in PTEN. Future studies are needed to clarify the prognostic significance of each cerebral phenotype, but overall, we conclude that despite a high burden of neurodevelopmental disease, long-term outcomes may be favorable. Germline testing for PTEN mutations should be considered in cases of megalencephaly and cortical brain malformations even in the absence of other findings, including cognitive impairment.
Topics: Humans; Autism Spectrum Disorder; Phosphatidylinositol 3-Kinases; Retrospective Studies; Megalencephaly; Brain; Polymicrogyria; PTEN Phosphohydrolase
PubMed: 37619436
DOI: 10.1016/j.pediatrneurol.2023.06.015 -
Brain Communications 2023Polymicrogyria is estimated to be one of the most common brain malformations, accounting for ∼16% of malformations of cortical development. However, the prevalence and...
Polymicrogyria is estimated to be one of the most common brain malformations, accounting for ∼16% of malformations of cortical development. However, the prevalence and incidence of polymicrogyria is unknown. Our aim was to estimate the prevalence, incidence rate, neuroimaging diversity, aetiology, and clinical phenotype of polymicrogyria in a population-based paediatric cohort. We performed a systematic search of MRI scans at neuroradiology department databases in Stockholm using the keyword polymicrogyria. The study population included all children living in the Stockholm region born from January 2004 to June 2021 with polymicrogyria. Information on the number of children living in the region during 2004-21 was collected from records from Statistics Sweden, whereas the number of births for each year during the study period was collected from the Swedish Medical Birth Register. All MRI scans were re-evaluated, and malformations were classified by a senior paediatric neuroradiologist. The prevalence and yearly incidence were estimated. Clinical data were collected from medical records. A total of 109 patients with polymicrogyria were included in the study. The overall polymicrogyria prevalence in Stockholm was 2.3 per 10 000 children, and the overall estimated yearly incidence between 2004 and 2020 was 1.9 per 10 000 person-years. The most common polymicrogyria distribution was in the frontal lobe (71%), followed by the parietal lobe (37%). Polymicrogyria in the peri-sylvian region was observed in 53%. Genetic testing was performed in 90 patients revealing pathogenic variants in 32%. Additionally, 12% had variants of uncertain significance. Five patients had a confirmed congenital infection, and in six individuals, the cause of polymicrogyria was assumed to be vascular. Epilepsy was diagnosed in 54%. Seizure onset during the first year of life was observed in 44%. The most common seizure types were focal seizures with impaired awareness, followed by epileptic spasms. Thirty-three of 59 patients with epilepsy (56%) were treated with more than two anti-seizure medications, indicating that pharmacoresistant epilepsy is common in polymicrogyria patients. Neurodevelopmental symptoms were observed in 94% of the individuals. This is the first population-based study on polymicrogyria prevalence and incidence. Confirmed genetic aetiology was present in one-third of individuals with polymicrogyria. Epilepsy was common in this patient group, and the majority had pharmacoresistant epilepsy. These findings increase our knowledge about polymicrogyria and will help in counselling patients and their families.
PubMed: 37614989
DOI: 10.1093/braincomms/fcad213 -
International Journal of Developmental... Nov 2023Cortical development depends on neuronal migration of both excitatory and inhibitory interneurons. Neuronal migration disorders (NMDs) are conditions characterised by... (Review)
Review
Cortical development depends on neuronal migration of both excitatory and inhibitory interneurons. Neuronal migration disorders (NMDs) are conditions characterised by anatomical cortical defects leading to varying degrees of neurocognitive impairment, developmental delay and seizures. Refractory epilepsy affects 15 million people worldwide, and it is thought that cortical developmental disorders are responsible for 25% of childhood cases. However, little is known about the epidemiology of these disorders, nor are their aetiologies fully understood, though many are associated with sporadic genetic mutations. In this review, we aim to highlight X-linked NMDs including lissencephaly, periventricular nodular heterotopia and polymicrogyria because of their mostly familial inheritance pattern. We focus on the most prominent genes responsible: including DCX, ARX, FLNA, FMR1, L1CAM, SRPX2, DDX3X, NSHDL, CUL4B and OFD1, outlining what is known about their prevalence among NMDs, and the underlying pathophysiology. X-linked disorders are important to recognise clinically, as females often have milder phenotypes. Consequently, there is a greater chance they survive to reproductive age and risk passing the mutations down. Effective genetic screening is important to prevent and treat these conditions, and for this, we need to know gene mutations and have a clear understanding of the function of the genes involved. This review summarises the knowledge base and provides clear direction for future work by both scientists and clinicians alike.
Topics: Female; Humans; Epilepsy; Sex Factors; Genetic Testing; Mutation; Malformations of Cortical Development, Group II; Fragile X Mental Retardation Protein; Cullin Proteins
PubMed: 37574439
DOI: 10.1002/jdn.10290