Corpus callosal agenesis with gray matter heterotopia and bilateral eye coloboma in an infant: A case report.

Corpus callosal agenesis (CCA) is a rare congenital disorder characterized by the partial or complete absence of the corpus callosum, a structure crucial for interhemispheric communication. CCA can occur in isolation or be associated with other anomalies such as heterotopia, holoprosencephaly, cerebellar hypoplasia, coloboma, and hydrocephalus. The prevalence of CCA ranges from 0.020% to 0.025%, though some reports suggest higher rates. This case report describes a 1-year-old male with developmental delays and no significant antenatal or family history. MRI revealed a complete absence of the corpus callosum, asymmetrically dilated lateral ventricles, subependymal gray matter nodules suggestive of gray matter heterotopia, and bilateral posterior globe defects with vitreous herniation, indicating severe ocular anomalies. The child received supportive care including physical therapy and special education services, with regular follow-ups for developmental and ophthalmologic evaluation. This case report details the rare occurrence of CCA, accompanied by gray matter heterotopia and bilateral posterior eye coloboma in a pediatric patient. The combination of these congenital anomalies presents unique diagnostic and management challenges requiring multidisciplinary care. We discuss the clinical presentation, radiological findings, and implications for supportive care and improving the prognosis.

Optimal testing time for cerebral heterotopia formation in the rat comparative thyroid assay, a downstream indicator for perinatal thyroid hormone insufficiency.

In a past study, we proposed a modified Comparative Thyroid Assay (CTA) with additional examinations of brain thyroid hormone (TH) concentrations and brain histopathology but with smaller group sizes. The results showed that the modified CTA in Sprague Dawley rats detected 10 ppm 6-propylthiouracil (6-PTU)-induced significant suppressions of serum/brain TH concentrations in offspring. To confirm the reliability of qualitative brain histopathology and identify the optimal testing time for heterotopia (a cluster of ectopic neurons) in the modified CTA, brain histopathology together with serum/brain TH concentrations were assessed in GD20 fetuses and PND2, 4, 21, and 28 pups using a similar study protocol but with a smaller number of animals (N=3-6/group/time). Significant hypothyroidism was observed and brain histopathology revealed cerebral heterotopia formation in PND21 and PND28 pups, with likely precursor findings in PND2 and PND4 pups but not in GD20 fetuses. This study confirmed that the optimal testing time for cerebral heterotopia in rat CTA was PND21 and thereafter. These findings suggest that cerebral heterotopia assessment at appropriate times may be a useful alternative to the original CTA design.

FEVR combined with macular heterotopia in children presenting as pseudo-exotropia: a case report and literature review.

Familial exudative retinopathy (FEVR) is a hereditary disease involving abnormal retinal vascular development in which macular heterotopia (MH) caused by mechanical-like pulling of the vitreous may lead to pseudo-strabismus. We describe the case of a 12-year-old male patient from China who presented to our hospital with a request for surgical correction of exotropia. Examination revealed that the strabismic appearance was due to MH, and dilated pupil examination of the peripheral fundus revealed that the blood vessels of the left eye and the macula were displaced toward the temporal retina by pulling, and further FFA examination was performed to diagnose FEVR. With good binocular vision and stereoscopic distance vision, corrective surgery for strabismus in this patient would have resulted in a hard-to-resolve diplopia. Therefore, it is important to identify FEVR combined with MH in clinical practice to avoid wrong diagnostic and treatment options.

A familial case of diffuse periventricular nodular heterotopia identified prenatally: Filamin A defect as the probable cause.

Periventricular nodular heterotopia (PNH) is a neuronal migration defect characterized by the presence of ectopic grey matter nodules adjacent to the walls of the lateral ventricles. The main genetic etiology of PNH are variants in the Filamin A gene (FLNA, MIM #300049), located in the X chromosome. It affects mostly females (embryonic lethality in males), with about 50% of cases inherited from healthy mothers or with a mild phenotype. It is associated with epilepsy (75%-90%), cardiovascular (65%) and pulmonary pathologies (25%). A 28-year-old primigravida was referred for prenatal care in obstetrics department because of personal history of obliterative bronchiolitis. She has a family history of asthma (mother and sister) and adulthood-onset epilepsy (father). The pregnancy was uneventful up to 20 weeks and 3 days when bilateral periventricular irregularities and mega cisterna magna were identified on ultrasound in a female fetus. Neurosonography was performed, which led to the hypothesis of diffuse PNH, supported by MRI. The hypothesis of PNH associated to the FLNA gene was made. Brain MRI on the pregnant woman was requested, which confirmed a similar pattern of PNH. The arrayCGH (PerkinElmer, Prenatal filter 37K) was normal, and whole exome sequencing identified the likely pathogenic c.1554del p.(Val519fs*) variant in the FLNA gene. We present a case of X-linked hereditary PNH that highlights the value of fetal neurosonography in making a putative diagnosis. The diagnosis was supported by MRI in both fetus and mother. The investigation was supplemented by genetic studies, which confirmed the diagnosis.

Ectopic Posterior Pituitary and Its Associations with Extrapituitary Intracranial Anomalies.

Posterior pituitary ectopia is a very rare entity in the development of the pituitary gland. Several factors and multiple genes are associated with this entity causing both pituitary and extrapituitary abnormalities. Pituitary abnormalities can be various endocrine problems and extrapituitary abnormalities can be optic nerves and cerebellar hypoplasia, heterotopia, and abnormal vessels. This pictorial review represents the imaging manifestations of extrapituitary intracranial anomalies that can be associated with posterior pituitary ectopia.

Characterisation of Kürsteiner canals of parathyroid: imparting relevance to a one-and-a-quarter-century-old concept.

AIMS: Kürsteiner canals (KC) were described at least 125 years ago as pharyngeal pouch embryological remnants of parathyroid and thymic development. While considered precursors for a subset of parathyroid cysts and salivary heterotopias (SH), they remain enigmatic. We now define a comprehensive phenotype of KC remnants and investigate their role in a spectrum of parathyroid lesions. METHODS AND RESULTS: `Sixty-two cystic and 22 non-cystic parathyroid lesions (73 patients) were retrieved from our institutional archive (2011-23) and evaluated for the presence of KC and prevalence of KC phenotype in parathyroid hormone (PTH)-positive and PTH-negative cysts. KC phenotype was defined as: cysts and tubules with surrounding sclerosis; bland, unilayered lining with frequent nuclear indentation of lumina; vesicular chromatin relative to chief cells; attenuated eosinophilic to 'hyper-cleared' cytoplasm; and staining pattern PTH-negative, SOX-10-positive, CK7-positive, GATA-3-positive and PAX-9 dim, a subset with oestrogen/progesterone receptor (ER/PR) positivity. Thirty PTH-negative cysts were identified in the neck/mediastinum; 14 of this group also showed SH. Thirty-two PTH-positive cysts included: 11 cystic parathyroid adenomas, 17 hyperplastic parathyroids, and four carcinomas. KC showed two distinct subtypes and were often found near PTH-negative cysts. PTH-negative cysts were associated with inferior parathyroids, SOX-10 positivity, fibrosclerosis, vesicular nuclei indenting cyst lumina and hyper-cleared or attenuated eosinophilic cytoplasm. CONCLUSIONS: KC are common in parathyroids and show a distinct histological and immunohistochemical profile, with an inferior predilection favouring branchial cleft III distribution. Diagnostically, the high prevalence of this phenotype in PTH-negative cysts and salivary heterotopia supports derivation of non-functioning cysts from KC. Conversely, PTH-positive cysts are more compatible with cystic change within hyperfunctioning glands.

A Case of Epicardial Epidermoid Cyst in a Crested Porcupine.

The crested porcupine (Hystrix cristata) is present in central Italy with an estimated population of 1800 individuals. Despite the local abundance, little data are available on the diseases affecting free-ranging individuals. We describe a case of an epidermoid cyst (EC) in a male adult porcupine found in the municipality of Sovicille, province of Siena (Tuscany). At necropsy, a firm rounded nodule was noted on the left ventricle wall. Histological examination revealed a cystic formation lined by stratified squamous epithelium. The cyst was filled with lamellar keratin, while hair shafts were not present. The adjacent epicardium was infiltrated by lymphoplasmacytic cells in reaction to the rupture of the cyst with the spilling of keratinaceous debris. The lesion was diagnosed as a ruptured epicardial epidermoid cyst. EC are most commonly found in the skin, both in human and animal patients, though infrequently, they can occur in any internal organ. Cardiac EC has not been reported in domestic animals, and this is the first report of EC in a wild animal species. Clinical veterinarians should consider the possibility of similar cardiac lesions in captive subjects since the long lifespan of these rodents could allow the growth of the cyst with the compression of the adjacent tissues.

Heterotopic neuroglial mass in the parapharyngeal space causing dysphagia in a 4 years old child: A case report.

INTRODUCTION: Neuroglial heterotopia represents a rare differential diagnosis for pediatric neck masses. Its occurrence in the parapharyngeal space is exceptionally uncommon, with fewer than 30 documented cases in the literature. CASE REPORT: This report details the case of a 4-year-old girl initially noted to have a mass in the right parotid area at birth with no symptoms. After observation, she returned at the age of 4 with dysphagia and a visible mass in the same area. Subsequent CT imaging revealed a mass in the right parapharyngeal space, prompting surgical intervention. Histological examination after resection confirmed the diagnosis of neuroglial heterotopia. DISCUSSION: Neuroglial heterotopia manifests with various symptoms in pediatric patients, posing diagnostic challenges due to the lack of specific radiological or clinical features distinguishing it from other neck masses in children. CONCLUSION: This case highlights the significance of considering neuroglial heterotopia in pediatric neck region masses diagnoses. Further research is needed to better understand its clinical features and treatment options.

Atypical Extraoral Presentation of a Heterotopic Gastrointestinal Cyst on the Face: A Case Report.

Heterotopias and choristomas are congenital lesions characterized by the presence of histologically normal tissues at non-physiological anatomic sites. The presence of gastrointestinal tissue in the oral cavity has been recognized as a heterotopic gastrointestinal cyst (HGIC) of the oral cavity. An intestinal heterotopia on the face, in relation to the parotid gland, is extremely rare. Highlighting this possibility is the case of a 42-year-old, non-habitué female with swelling in the parotid region of the face for two years. Clinical examination and radiographic investigations ruled out the possibility of a salivary gland tumor, epidermal inclusion cyst, and enlarged parotid lymph node while confirming the cystic nature of the presenting pathology. Further evaluation was carried out using an excisional biopsy. Histopathological evaluation revealed a cystic space lined by simple columnar epithelium with an abundance of goblet cells. The cystic epithelium was noted to form finger-like projections and crypts. An eosinophilic mucinous content was noted in the cystic space. Using Alcian blue-periodic acid-Schiff (PAS) staining, a distinct Alcian blue positivity of the mucinous material and the goblet cells was noted. This feature confirms the acidic nature of the mucinous content being liberated by the goblet cells. The histopathological features, along with histochemical assessment, were confirmatory for the diagnosis of an HGIC. The patient remains disease-free at the end of a 12-month follow-up. This is the first report of an HGIC at an extraoral site on the face in association with the parotid gland. It highlights the possible presentation of heterotopias in adult patients and warrants clinicopathological vigilance due to its benign nature and late presentation.

Rare Causes of Gastrointestinal Hemorrhage: A Case Series of Adult Duodenal and Jejunal Gastric Heterotopia.

Gastric heterotopia (GH) is a rare cause of gastrointestinal bleeding. GH of the small bowel is rare, and the duodenum is more commonly involved than the jejunum. Here, we present five cases of GH involving the duodenum and jejunum, with presentations including gastrointestinal bleeding, symptomatic anemia, and no symptoms. A 63-year-old man presented with melenic stools but could not identify an obvious bleeding source during endoscopy. He was ultimately diagnosed with jejunal GH. A 70-year-old woman with melena and severe anemia had a duodenal bulb mass detected during endoscopy, which was histopathologically diagnosed as GH. A 54-year-old woman experienced nausea, vomiting, and dysphagia. Endoscopy revealed esophagitis and a duodenal GH without malignancy. A 69-year-old woman incidentally had duodenal GH during evaluation for a lung mass, which was later diagnosed as an aggressive neuroendocrine tumor. The fifth patient was an 83-year-old woman who was admitted for profound significant anemia. Upper endoscopy showed a round, 0.3 cm ulcer in the duodenum and a duodenal polyp with a tiny ulcer, and her histopathology was consistent with GH. The exact mechanism of the action of GH remains unknown. Its clinical presentation is variable, gastrointestinal bleeding is rare, and diagnosis is based on histopathology only. Our case series emphasizes the need to include GH in the differential diagnosis of patients presenting with gastrointestinal bleeding, with or without other associated symptoms.

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.

Double Cortex Syndrome: An Unusual Cause of Seizures.

Gray matter heterotopia (GMH) is caused by abnormal neuronal migration during brain development. Subcortical band heterotopia (SBH), or double cortex, is a rare variant of GMH that mainly affects female patients with epilepsy (PWE) with different degrees of mental retardation. We present the case of a 25-year-old woman who was admitted to the neurology department of our tertiary hospital with generalized tonic-clonic seizures. Her mother had a normal antenatal period and a history of labor. There was a history of immediate crying and normal appearance, pulse, grimace, activity, and respiration (APGAR) scores. She had delayed milestones, which affected various categories of child development. Physical examination revealed a global developmental delay. Laboratory values, including complete blood count, serum calcium, and arterial blood gas tests, were all within normal limits. An EEG showed significant abnormalities suggestive of epilepsy. An MRI of the brain showed a continuous band of gray matter located deep and parallel to the cortex in both cerebral hemispheres, suggesting double cortex syndrome (DCS).

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.

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.

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.

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.