Regulated Pandemic Spaces: Spatial Crises in COVID Comics.

Close-reading sequential comics and cartoons such as He Zhu's "Lockdown," Rivi Handler-Spitz's "Morning Commute," Yang Ji's "Quarantine," and Thi Bui, Will Evans, Sarah Mirk, Amanda Pike, and Esther Kaplan's "In/Vulnerable," this article investigates the networked spatial crises that have emerged during COVID-19. As the global pandemic reshaped social, economic, and cultural landscapes, it is crucial to understand the spatial implications of these transformations. By analyzing graphic medical texts, which serve as visual narratives that capture the lived experiences and perceptions of individuals within these crises, the present essay offers a nuanced exploration of the intricate relationships between space, society, and the effects of the pandemic. The article identifies and examines the various spatial crises that have emerged in the COVID era, such as disrupted urban environments, altered social dynamics, spaces of contamination, contraction of space, and the reconfiguration of workspaces. Drawing on theorists like Michael Foucault and Henri Lefebvre, this essay illustrates how these crisis-induced spatial transformations are represented, experienced, and contested. Ultimately, the article not only contributes to a deeper understanding of the complex interplay between the pandemic and space but also addresses the challenges of our evolving world.

Laser interstitial thermal therapy of a single nodule in a complex epileptic network with multiple periventricular nodular heterotopias.

Surgical management of drug-resistant epilepsy (DRE) in patients with multiple periventricular nodular heterotopias (PVNHs) is challenging. Identifying the location of seizure onset within these complex epileptic networks is difficult, and open resection carries risks of injury to surrounding functional white matter tracts such as optic radiations (ORs). The authors demonstrate tractography-assisted laser ablation of a single nodule in a patient with DRE and multiple PVNHs. Following surgery, visual fields were intact, highlighting the benefits of OR tractographic reconstruction. At 12 months postoperatively, the patient remained seizure free, suggesting the potential efficacy of targeting a single heterotopia within complex networks in well-selected cases. The video can be found here: https://stream.cadmore.media/r10.3171/2024.4.FOCVID2417.

Patient-specific mutation of Dync1h1 in mice causes brain and behavioral deficits.

AIMS: Cytoplasmic dynein heavy chain (DYNC1H1) is a multi-subunit protein complex that provides motor force for movement of cargo on microtubules and traffics them back to the soma. In humans, mutations along the DYNC1H1 gene result in intellectual disabilities, cognitive delays, and neurologic and motor deficits. The aim of the study was to generate a mouse model to a newly identified de novo heterozygous DYNC1H1 mutation, within a functional ATPase domain (c9052C > T(P3018S)), identified in a child with motor deficits, and intellectual disabilities. RESULTS: P3018S heterozygous (HET) knockin mice are viable; homozygotes are lethal. Metabolic and EchoMRI™ testing show that HET mice have a higher metabolic rate, are more active, and have less body fat compared to wildtype mice. Neurobehavioral studies show that HET mice perform worse when traversing elevated balance beams, and on the negative geotaxis test. Immunofluorescent staining shows neuronal migration abnormalities in the dorsal and lateral neocortex with heterotopia in layer I. Neuron-subtype specific transcription factors CUX1 and CTGF identified neurons from layers II/III and VI respectively in cortical layer I, and abnormal pyramidal neurons with MAP2+ dendrites projecting downward from the pial surface. CONCLUSION: The HET mice are a good model for the motor deficits seen in the child, and highlights the importance of cytoplasmic dynein in the maintenance of cortical function and dendritic orientation relative to the pial surface. Our results are discussed in the context of other dynein mutant mice and in relation to clinical presentation in humans with DYNC1H1 mutations.

Unveiling Nasal Glial Heterotopia: A Pathological Perspective.

The uncommon, non-hereditary congenital abnormalities known as nasal glial heterotopias (NGH) are composed of heterotopic neuroglial tissue. Typically, NGH manifests in infancy, but occasionally it can also be seen in older children and adults. To rule out intracranial extension, magnetic resonance imaging (MRI) and computed tomography (CT) scans should be performed. Numerous cases have been documented where NGH was mistakenly identified as encephaloceles, teratomas, dermoid cysts, capillary haemangiomas, and even desmoids. A proper clinical, sonological, and even CT and MRI evaluation can lead to a near-final diagnosis; nonetheless, surgical excision and histological confirmation are the gold standards. We report a rare case of a firm, subcutaneous, non-tender, non-reducible midline 2 x 2 x 1 cm swelling with bluish-red skin near the root of the nose that was not affected by posture or pressure. Encephalocele, NGH, and dermoid were the differential diagnoses made based on the oedema found on CT and MRI scans. Histopathology provided a conclusive NGH diagnosis. The instance illustrates the significance of histology as the gold standard for NGH diagnosis.

Heterotopic Pancreas: Unusual Cause of Usual Diarrhoea.

Heterotopic pancreas (HP) also known as ectopic pancreas, pancreatic crest or accessory pancreas is the normal pancreatic tissue, found in a remote area other than its natural location, with no anatomic or vascular connection to main pancreatic tissue. It is a rare congenital anomaly and has been reported at many locations such as stomach (antrum) and small intestine. HP is usually an incidental finding and asymptomatic, however there are reports of pancreatitis, obstruction, perforation and malignant transformation as uncommon manifestations. Diagnosis of HP is primarily based on histological examination either by biopsy or surgical excision. Surgery is the standard treatment for symptomatic HP patients. Herein, we present a case of a 58-year-old female, who presented to us with intractable diarrhoea due to HP in the jejunum and underwent minimally invasive surgery for definitive diagnosis and treatment.

Jejunal Ectopic Pancreatic Tissue Rest as Lead Point in Patients with Intussusception: A Rare Case Report and Review of Literature.

Background: Ectopic pancreas (EP), characterized by pancreatic tissue outside its usual location, poses diagnostic challenges due to its asymptomatic nature in most cases. Gastric lesions are often symptomatic, causing epigastric pain or gastric outlet obstruction. Rarely, jejunal lesions can lead to intestinal obstruction or intussusception. The elusive preoperative diagnosis lacks specific biochemical markers, relying on intraoperative biopsy and histopathology as gold standards. Case Presentation: We present a unique case of a 37-year-old female with 12-hour crampy abdominal pain, bilious vomiting, blood-mixed diarrhea, abdominal distension, and obstructive symptoms. Imaging revealed jejunojejunal intussusception with a jejunal mass as the lead point. Intraoperatively, also identified jejunal mass as lead point. Resection of mass and end-to-end jejunojejunal anastomosis were performed, resulting in a successful outcome. Histopathological examination identified a type I ectopic pancreas within the muscularis propria. Twelve months postoperatively, the patient exhibited no stricture or recurrence. Conclusion: Ectopic pancreas, with varied symptoms, poses diagnostic hurdles. Despite the diagnostic challenges, surgical excision remains the optimal treatment for symptomatic cases. This report contributes to the limited literature on ectopic pancreas, emphasizing the importance of considering this entity in the differential diagnosis of gastrointestinal pathology.

Phenotypic Variability in Novel Doublecortin Gene Variants Associated with Subcortical Band Heterotopia.

Doublecortin, encoded by the DCX gene, plays a crucial role in the neuronal migration process during brain development. Pathogenic variants of the DCX gene are the major causes of the "lissencephaly (LIS) spectrum", which comprehends a milder phenotype like Subcortical Band Heterotopia (SBH) in heterozygous female subjects. We performed targeted sequencing in three unrelated female cases with SBH. We identified three DCX-related variants: a novel missense (c.601A>G: p.Lys201Glu), a novel nonsense (c.210C>G: p.Tyr70*), and a previously identified nonsense (c.907C>T: p.Arg303*) variant. The novel c.601A>G: p.Lys201Glu variant shows a mother-daughter transmission pattern across four generations. The proband exhibits focal epilepsy and achieved seizure freedom with a combination of oxcarbazepine and levetiracetam. All other affected members have no history of epileptic seizures. Brain MRIs of the affected members shows predominant fronto-central SBH with mixed pachygyria on the overlying cortex. The two nonsense variants were identified in two unrelated probands with SBH, severe drug-resistant epilepsy and intellectual disability. These novel DCX variants further expand the genotypic-phenotypic correlations of lissencephaly spectrum disorders. Our documented phenotypic descriptions of three unrelated families provide valuable insights and stimulate further discussions on DCX-SBH cases.

Microscopic sex cord-stromal proliferations in extraovarian heterotopic sites: Report of a rare case and review of the literature.

Microscopic heterotopic extraovarian sex cord-stromal proliferations were first reported in the literature in 2015 by McCluggege. Afterwards, few similar cases have been described. Herein, we report the fourteenth case of microscopic heterotopic sex cord-stromal proliferation and the third case sited in the pelvic peritoneum. The clinical history of these rare cases suggests their benign nature. Knowledge of this histological pattern is important for differential diagnoses such as malignant pathologies and metastatic diseases.

Periventricular nodular heterotopia in patients with a prenatal diagnosis of myelomeningocele/myeloschisis: associations with seizures and neurodevelopmental outcomes during early childhood.

PURPOSE: Historically, the presence of gray matter heterotopia was a concern for adverse postnatal neurocognitive status in patients undergoing fetal closure of open spinal dysraphism. The purpose of this study was to evaluate neurodevelopmental outcomes and the onset of seizures during early childhood in patients with a prenatal diagnosis of myelomeningocele/myeloschisis (MMC) and periventricular nodular heterotopia (PVNH). METHODS: All patients evaluated at the Center for Fetal Diagnosis and Treatment with a diagnosis of MMC between June 2016 to March 2023 were identified. PVNH was determined from prenatal and/or postnatal MRI. The Bayley Scales of Infant and Toddler Development (edition III or IV) were used for neurodevelopmental assessments. Patients were screened for seizures/epilepsy. RESULTS: Of 497 patients evaluated with a prenatal diagnosis of MMC, 99 were found to have PVNH on prenatal MRI, of which 35 had confirmed PVNH on postnatal imaging. From the 497 patients, 398 initially did not exhibit heterotopia on prenatal MRI, but 47 of these then had confirmed postnatal PVNH. The presence of PVNH was not a significant risk factor for postnatal seizures in early childhood. The average neurodevelopmental scores were not significantly different among heterotopia groups for cognitive, language, and motor domains. CONCLUSION: The presence of PVNH in patients with a prenatal diagnosis of MMC does not indicate an increased risk for neurodevelopmental delay at 1 year of age. We did not demonstrate an association with seizures/epilepsy. These findings can aid clinicians in prenatal consultation regarding fetal repair of open spinal dysraphism. Long-term follow-up is required to discern the true association between PVNH seen on prenatal imaging and postnatal seizures/epilepsy and neurodevelopmental outcomes.

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.

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.

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.

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.

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 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.