RELN gene-related drug-resistant epilepsy with periventricular nodular heterotopia treated with radiofrequency thermocoagulation: a case report.

An increasing number of gene mutations associated with epilepsy have been identified, some linked to gray matter heterotopia-a common cause of drug-resistant epilepsy. Current research suggests that gene mutation-associated epilepsy should not be considered a contraindication for surgery in epilepsy patients. At present, stereoelectroencephalography-guided radiofrequency thermocoagulation is an important method to treat periventricular nodular heterotopia-associated drug-resistant epilepsy. We present a case of drug-resistant epilepsy, accompanied by periventricular nodular heterotopia and a heterozygous mutation of the RELN gene, successfully treated with radiofrequency thermocoagulation, resulting in a favorable outcome.

Retroperitoneal neuroglial heterotopia: a case report and literature review.

Background: Neuroglial heterotopia is a rare lesion composed of differentiated neuroectodermal cells that manifest in extracranial locations, with the majority of cases predominantly occurring in the head and neck region. Retroperitoneal neuroglial heterotopia is exceptionally rare, with isolated cases published in the scientific literature. Case report: Here, we present the case of a 3-year-old girl who was admitted without clinical signs but presented with a palpable abdominal mass. Ultrasonography and computed tomography scans revealed a sizable cystic lesion within the retroperitoneal space. Subsequently, laparoscopic resection was performed. Histological examination unveiled neuroglial cell-lined cysts encompassing fibrous connective tissue, ganglia, glial tissue, and nerve bundles. Notably, distinct areas and cell types exhibited expression of S100, glial fibrillary acidic protein, and neuron-specific enolase. Follow-up assessments revealed no relapses or late complications. Conclusion: In cases of retroperitoneal neuroglial heterotopia, most children may remain asymptomatic without any congenital anomalies. Despite their detectability through imaging, accurate preoperative diagnosis is seldom achieved. Generally, a favorable prognosis follows complete surgical resection, although further cases are required to confirm its long-term efficacy, necessitating extended follow-up for verification.

Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders.

BACKGROUND: Thousand and one amino-acid kinase 1 (TAOK1) encodes the MAP3K protein kinase TAO1, which has recently been displayed to be essential for neuronal maturation and cortical differentiation during early brain development. Heterozygous variants in TAOK1 have been reported in children with neurodevelopmental disorders, with or without macrocephaly, hypotonia and mild dysmorphic traits. Literature reports lack evidence of neuronal migration disorders in TAOK1 patients, although studies in animal models suggest this possibility. CASE PRESENTATION: We provide a clinical description of a child with a neurodevelopmental disorder due to a novel TAOK1 truncating variant, whose brain magnetic resonance imaging displays periventricular nodular heterotopia. CONCLUSIONS: To our knowledge, this is the first report of a neuronal migration disorder in a patient with a TAOK1-related neurodevelopmental disorder, thus supporting the hypothesized pathogenic mechanisms of TAOK1 defects.

ILAE neuroimaging task force highlight: Subcortical laminar heterotopia.

The ILAE Neuroimaging Task Force publishes educational case reports that highlight basic aspects of neuroimaging in epilepsy consistent with the ILAE's educational mission. Subcortical laminar heterotopia, also known as subcortical band heterotopia (SBH) or "double cortex," is an intriguing and rare congenital malformation of cortical development. SBH lesions are part of a continuum best designated as agyria-pachygyria-band-spectrum. The malformation is associated with epilepsy that is often refractory, as well as variable degrees of developmental delay. Moreover, in an increasing proportion of cases, a distinct molecular-genetic background can be found. Diagnosing SBH can be a major challenge for many reasons, including more subtle lesions, and "non-classic" or unusual MRI-appearances. By presenting an illustrative case, we address the challenges and needs of diagnosing and treating SBH patients in epilepsy, especially the value of high-resolution imaging and specialized MRI-protocols.

Cerebellar Heterotopia: Broadening the Neuroradiological Spectrum of KBG Syndrome.

KBG syndrome is a rare genetic disorder caused by heterozygous pathogenic variants in ANKRD11. Affected individuals have developmental delay, short stature, characteristic facial features, and other dysmorphic findings. To date, a spectrum of unspecific neuroradiological defects has been reported in KBG patients, such as cortical defects, white matter abnormalities, corpus callosum, and cerebellar vermis hypoplasia.Deep clinical and neuroradiological phenotyping and genotype of a patient presenting with mild cognitive and behavioral problems were obtained after written informed consent.We herein describe the first KBG patient presenting with cerebellar heterotopia, a heterogeneous malformation characterized by the presence of clusters of neurons within the white matter of cerebellar hemispheres.This novel association broadens the neuroradiological spectrum of KBG syndrome, and further prompts to investigate the potential functions of ANKRD11 in cerebellar development.

Cerebellar heterotopia in an 11-year-old child with KDM6B-related neurodevelopmental disorder: A case report and review of the literature.

Heterozygous pathogenic variants in KDM6B have recently been associated to a rare neurodevelopmental disorder referred to as "Neurodevelopmental disorder with coarse facies and mild distal skeletal abnormalities" and characterized by non-pathognomonic facial and body dysmorphisms, a wide range of neurodevelopmental and behavioral disorders and nonspecific neuroradiological findings. KDM6B encodes a histone demethylase, expressed in different tissues during development, which regulates gene expression through the modulation of chromatin accessibility by RNA polymerase. We herein describe a 11-year-old male patient carrying a novel de novo pathogenic variant in KDM6B exhibiting facial dysmorphisms, dysgraphia, behavioral traits relatable to oppositional defiant, autism spectrum, and attention deficit hyperactivity disorders, a single seizure episode, and a neuroimaging finding of a single cerebellar heterotopic nodule, never described to date in this genetic condition. These findings expand the phenotypic spectrum of this syndrome, highlighting the potential role for KDM6B in cerebellar development and providing valuable insights for genetic counseling.

Oral Gastric Heterotopia: First Reported Case in the Hard Palate.

Gastric heterotopia is characterized by the presence of mature gastric tissue outside the stomach, yet its occurrence in the palate has not been previously documented. We describe a case of gastric heterotopia in the hard palate of an elderly female patient, presenting as a swollen mass with associated secretion. Given the patient's age and clinical symptoms, a presumptive diagnosis of a malignant tumor originating from the minor salivary glands was made. An incisional biopsy of the mass revealed gastric heterotopia. Subsequently, the extended excision of the lesion was performed, leading to the full resolution of the patient's symptoms. After a two-year follow-up period, no evidence of recurrence was observed. The importance of this case, underscored by the unprecedented location of gastric heterotopia, emphasizes the critical need for thorough evaluation to avert misdiagnosis, as well as the complete surgical excision of the lesion to prevent recurrence.

Upper Urothelial Tract Extraosseous Bone Formation: An Unexpected Finding and Differential Diagnostic Considerations.

Extraosseous bone formation of the upper urothelial tract is an unusual phenomenon with limited documentation in the uropathology literature, reported in only 2 clinical series of patients undergoing percutaneous nephrolithotomy for the management of renal stones. While speculations regarding the pathogenesis of this occurrence have been published, heterotopic ossification is still poorly understood. We report the finding of extraosseous bone formation in the renal pelvis of a 30-year-old male patient with a history of kidney stones. Histologic sections of the ureter and renal pelvis showed submucosal nodules of woven bone. Ancillary fluorescence in-situ hybridization studies were negative for MDM2 amplification and USP6 rearrangement.

Case report: Periventricular heterotopia and early-onset bipolar disorder in adolescent patient with history of childhood attention deficit hyperactivity disorder.

Periventricular heterotopia (PH) is a developmental malformation in the brain. Because the clinical symptoms are heterogeneous, few studies have investigated the psychiatric symptoms associated with PH. We describe the case of a 17-year-old male with bipolar disorder (BD), who had been treated for attention deficit-hyperactivity disorder (ADHD) and developmental delay in childhood. He had experienced depression for 1 year and was admitted to the emergency room following a suicide attempt. He was admitted to the psychiatric ward for further evaluation and treatment for elated mood, decreased need for sleep, increased sexuality, and delusion. The patient was diagnosed with BP-I disorder and PH via brain magnetic resonance imaging. After combined treatment with valproic acid and aripiprazole, his manic symptoms stabilized. To our knowledge, this is the first report of an adolescent PH case with a history of early onset BD and ADHD in childhood.

Grey matter heterotopia subtypes show specific morpho-electric signatures and network dynamics.

Grey matter heterotopia (GMH) are neurodevelopmental disorders associated with abnormal cortical function and epilepsy. Subcortical band heterotopia (SBH) and periventricular nodular heterotopia (PVNH) are two well-recognized GMH subtypes in which neurons are misplaced, either forming nodules lining the ventricles in PVNH, or forming bands in the white matter in SBH. Although both PVNH and SBH are commonly associated with epilepsy, it is unclear whether these two GMH subtypes differ in terms of pathological consequences or, on the contrary, share common altered mechanisms. Here, we studied two robust preclinical models of SBH and PVNH, and performed a systematic comparative assessment of the physiological and morphological diversity of heterotopia neurons, as well as the dynamics of epileptiform activity and input connectivity. We uncovered a complex set of altered properties, including both common and distinct physiological and morphological features across heterotopia subtypes, and associated with specific dynamics of epileptiform activity. Taken together, these results suggest that pro-epileptic circuits in GMH are, at least in part, composed of neurons with distinct, subtype-specific, physiological and morphological properties depending on the heterotopia subtype. Our work supports the notion that GMH represent a complex set of disorders, associating both shared and diverging pathological consequences, and contributing to forming epileptogenic networks with specific properties. A deeper understanding of these properties may help to refine current GMH classification schemes by identifying morpho-electric signatures of GMH subtypes, to potentially inform new treatment strategies.

DCX variants in two unrelated Chinese families with subcortical band heterotopia: Two case reports and review of literature.

Introduction: Subcortical band heterotopia (SBH) is a rare brain developmental malformation caused by deficient neuronal migration during embryogenesis. Published literature on pediatric SBH cases caused by DCX mutations is limited. Methods: The detailed clinical and genetic features of two pediatric SBH with DCX mutations were analyzed. The available literature on DCX mutations was reviewed. Results: Both patients were girls with varying degrees of developmental delay. Patient 1 was short in stature with peculiar facial features. Patient 2 had an early seizure onset and developed drug-resistant epilepsy. Whole-exome sequencing (WES) revealed two de novo heterozygous variants of DCX (NM_178153.3), including a novel missense variant of c.568A > G (p.K190E) in P1 and a reported nonsense variant of c.814C > T (p.R272*) in P2. We reviewed all the available literature regarding DCX mutations. A total of 153 different mutations have been reported, with the majority of 99 (64.7 %) being missense mutations. Conclusion: Our study expanded the mutational spectrum of DCX, which has important implications for the study of genotype-phenotype correlations. Furthermore, it provided insights to better understand SBH and genetic counseling.

Metabolic heterogeneity in different subtypes of malformations of cortical development causing epilepsy: a proton magnetic resonance spectroscopy study.

Background: The most common subtypes of malformations of cortical development (MCDs) are gray matter heterotopia (GMH), focal cortical dysplasia (FCD), and polymicrogyria (PMG). This study aimed to characterize the possible neurometabolic abnormalities and heterogeneity in different MCDs subtypes using proton magnetic resonance spectroscopy (1H-MRS). Methods: In this prospective cross-sectional study, we recruited 29 patients with MCDs and epilepsy, including ten with GMH, ten with FCD, and nine with PMG, as well as 25 age- and sex-matched healthy controls (HC) from the Epilepsy Center of West China Hospital of Sichuan University between August 2018 and November 2021. Inclusion criteria for the patients were based upon typical magnetic resonance imaging (MRI) findings of MCDs and full clinical assessment for epilepsy. Single-voxel point-resolved spectroscopy was used to acquire data from both the lesion and the normal-appearing contralateral side (NACS) in patients and from the frontal lobe in HC. Metabolite measures, including N-acetyl aspartate (NAA), myoinositol (Ins), choline (Cho), creatine (Cr), and glutamate + glutamine (Glx) concentrations, were quantitatively estimated with linear combination model (LCModel) software and corrected for the partial volume effect of cerebrospinal fluid (CSF). Results: The NAA concentration was lower and the Ins concentration was higher in the MCDs lesions than in the NACS and in HC (P=0.002-0.007), and the Cho and Cr concentrations were higher in MCDs lesions than in HC (P=0.001-0.016). Moreover, the Cho concentration was higher in NACS than in HC (P=0.015). In the GMH lesions, the only metabolic alteration was an NAA reduction (GMH_lesion vs. HC: P=0.001). In the FCD lesions, there were more metabolite abnormalities than in the other two subtypes, particularly a lower NAA and a higher Ins than in HC and NACS (P=0.012-0.042). In the PMG lesions, Cr (lesion vs. HC or NACS: P=0.017-0.021) and Glx (lesion vs. NACS: P=0.043) were increased, while NAA was normal. Correlation analysis revealed that the Cr concentration in MCDs lesions was positively correlated with seizure frequency (r=0.411; P=0.027). Conclusions: Based upon 1H-MRS, our study demonstrated that different MCDs subtypes exhibited variable metabolic features, which may be associated with distinct functional and cytoarchitectural properties.

Neocortical and cerebellar malformations affect flurothyl-induced seizures in female C57BL/6J mice.

Brain malformations cause cognitive disability and seizures in both human and animal models. Highly laminated structures such as the neocortex and cerebellum are vulnerable to malformation, affecting lamination and neuronal connectivity as well as causing heterotopia. The objective of the present study was to determine if sporadic neocortical and/or cerebellar malformations in C57BL/6J mice are correlated with reduced seizure threshold. The inhaled chemi-convulsant flurothyl was used to induce generalized, tonic-clonic seizures in male and female C57BL/6J mice, and the time to seizure onset was recorded as a functional correlate of brain excitability changes. Following seizures, mice were euthanized, and brains were extracted for histology. Cryosections of the neocortex and cerebellar vermis were stained and examined for the presence of molecular layer heterotopia as previously described in C57BL/6J mice. Over 60% of mice had neocortical and/or cerebellar heterotopia. No sex differences were observed in the prevalence of malformations. Significantly reduced seizure onset time was observed dependent on sex and the type of malformation present. These results raise important questions regarding the presence of malformations in C57BL/6J mice used in the study of brain development, epilepsy, and many other diseases of the nervous system.

[Intrauterine Device Totally Embedded in the Bladder Wall:Report of One Case].

Intrauterine device(IUD)migrating to the bladder is rare,especially the migration far away from the uterus into the bladder wall.Due to no obvious clinical symptom in the early stage and being far away from the uterus,the IUD totally embedded in the bladder wall is prone to misdiagnosis and delay in treatment.We reported one case of such migration,aiming to improve the clinical management of the IUD totally embedded in the bladder wall.

Surgical treatment of epilepsy in a patient with bilateral periventricular nodular heterotopia: A case report.

Background: Periventricular nodular heterotopia (PNH) is a rare pathological condition characterized by the presence of nodules of gray matter located along the lateral ventricles of the brain. The condition typically presents with seizures and other neurological symptoms, and various methods of surgical treatment and postoperative outcomes have been described in the literature. Case Description: We present a case study of a 17-year-old patient who has been experiencing seizures since the age of 13. The patient reported episodes of loss of consciousness and periodic freezing with preservation of posture. Two years later, the patient experienced his first generalized tonic-clonic seizure during nocturnal sleep and was subsequently admitted to a neurological department. A magnetic resonance imaging scan of the brain with an epilepsy protocol (3 Tesla) confirmed the presence of an extended bilateral subependymal nodular heterotopy at the level of the temporal and occipital horns of the lateral ventricles, which was larger on the left side, and a focal subcortical heterotopy of the right cerebellar hemisphere. The patient underwent a posterior quadrant disconnection surgery, which aimed to isolate the extensive epileptogenic zone in the left temporal, parietal, and occipital lobes using standard techniques. As of today, 6 months have passed since the surgery and there have been no registered epileptic seizures during this period following the surgical treatment. Conclusion: Although PNHs can be extensive and located bilaterally, surgical intervention may still be an effective way to achieve seizure control in selected cases.

The Differential Diagnosis of Congenital Developmental Midline Nasal Masses: Histopathological, Clinical, and Radiological Aspects.

Developmental midline nasal masses including nasal dermoids (NDs), encephaloceles (EPHCs), and nasal glial heterotopias (NGHs) are a consequence of disrupted embryonal developmental processes in the frontonasal region. Surgery is the only method of treatment in order to prevent local and intracranial inflammatory complications as well as distant deformities of the facial skeleton. Due to their rarity, similar location, and clinical and radiological symptoms, meticulous preoperative differential diagnostics is mandatory. The aim of this thorough literature review was to present and discuss all clinical, histopathological, and radiological aspects of NDs, NGHs, and EPHCs that are crucial for their differential diagnosis.

Midline cutaneous anomalies of the craniospinal axis.

Patients with midline cutaneous anomalies of the craniospinal axis can be indicative of underlying embryonic defects, such as neural tube defects. Lack of familiarity with these midline aberrant skin findings may lead to misdiagnosis and delayed treatment. In this review, midline cutaneous anomalies of the craniospinal axis including aplasia cutis congenita, cranial and spinal dysraphism, and other developmental anomalies are explored in detail with emphasis on cutaneous clues to the diagnosis and appropriate workup.

Gallbladder Pancreatic Heterotopia-The Importance of Diagnostic Imaging in Managing Intraoperative Findings.

Pancreatic heterotopy is a rare entity defined as the presence of abnormally located pancreatic tissue without any anatomical or vascular connection to the normal pancreas. Heterotopic pancreatic tissue can be found in various regions of the digestive system, such as the stomach, duodenum, and upper jejunum, with the less commonly reported location being the gallbladder. Gallbladder pancreatic heterotopia can be either an incidental finding or diagnosed in association with cholecystitis. Pancreatitis of the ectopic tissue has also been described. In this context, we report three cases of heterotopic pancreatic tissue in the gallbladder with different types of pancreatic tissue according to the Heinrich classification. One patient was a 24-year-old male who presented with acute pancreatitis symptoms and an ultrasonographical detected mass in the gallbladder, which proved to be heterotopic pancreatic tissue. The other two cases were female patients aged 24 and 32, respectively, incidentally diagnosed on histopathological examination after cholecystectomy for symptomatic cholelithiasis. Both cases displayed chronic cholecystitis lesions; one of them was also associated with low grade dysplasia of the gallbladder. Although a rare occurrence in general, pancreatic heterotopia should be acknowledged as a possible incidental finding in asymptomatic patients as well as a cause for acute cholecystitis or pancreatitis.

Glial Heterotopia of the Middle Ear: First Case in Indian Literature.

A 66-years-old female presented with impaired hearing of two-year duration and a recent ear discharge. High-resolution computed tomography and intra-operative findings showed a mass lesion in the right middle ear cavity that was unconnected with the brain. A histopathological diagnosis of glial heterotopia was made and an etiopathogenic hypothesis was analysed.