Subependymal Nodular Heterotopia Research Articles

Prenatal Diagnosis and Outcomes of Cervical Meningocele and Myelomeningocele.

Prenatal diagnosis of myelomeningocele remains challenging for obstetricians, ultrasonographers, and radiologists, although the increased maternal serum alpha-fetoprotein level aids in the confirmative diagnosis. Fetal cervical myelomeningocele and meningocele are very rare and unique types of myelomeningocele. Prenatal diagnosis of cervical myelomeningocele and meningocele should include the differential diagnosis and association of many intracranial and spino-skeletal pathogenetic variants and genetic diseases, including subependymal nodular heterotopia and Klippel-Feil syndrome. In this report, a comprehensive review of fetal cervical myelomeningocele with its prenatal diagnosis and long-term outcomes is presented.

Movement disorder and epilepsy in subependymal nodular heterotopia

Subependymal nodular heterotopia is a cortical development malformation that is commonly associated with refractory epilepsy. Patients with heterotopia show a wide spectrum of clinical manifestations, from being asymptomatic to presenting with intractable seizures and intellectual impairment.We report a case of refractory epilepsy with normal intelligence, having bilateral subependymal heterotopic nodules in brain, presenting to us with a movement disorder in the form of myoclonus of bilateral lower limbs which is an unusual manifestation of gray matter heterotopias.Though rare, gray matter heterotopias may present as movement disorder and should be considered in differential diagnosis while work up of movement disorders.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.

P173 Case report: rare cause of adult onset seizures identified in an HIV positive adult

Case ReportA 63-year-old male with a long history of poor social interactions presented acutely confused. There was no alcohol or recreational drug use. Baseline bloods and routine microbiology were normal....

A case report of surgically treated drug resistant epilepsy associated with subependymal nodular heterotopia

Subependymal nodular heterotopia (SNH) is a cortical development malformation that is commonly associated with medically resistant epilepsy. Cases of SNH are challenging to treat surgically because there are typically multiple nodules, which may be involved in epileptogenesis. Moreover, dual pathology may exist in these patients. Here, we present a case with unilateral subependymal heterotopic nodules associated with ipsilateral hippocampal atrophy. Invasive and non-invasive work-ups revealed that the hippocampus was the actual ictal onset zone and that the SNH was not involved. An anterior temporal lobectomy was carried out, and postoperative seizure outcome was class Ia at the end of 2 years. The case demonstrates that SNH may not play a major role in patients with dual pathology. However, direct electroencephalography (EEG) recording from areas of SNH and other possible epileptogenic regions is indispensable in defining the ictal onset zone and avoiding poor surgical outcomes.

Cervical meningocele associated with subependymal nodular heterotopia

Heterotopia is a subgroup of migration abnormalities, recognized by arrest of radial migration of neuroblasts. Being a well-known cause for developmental delay, mental retardation, and epilepsy, association of heterotopia with some other conditions has also been proposed. There are several case reports regarding the concurrence of heterotopia and encephalocele; however, no such association has been reported with cervical meningocele. Herein, we present the first case of periventricular nodular heterotopia associated with cervical meningocele. Our case further emphasizes the role of brain MRI in the evaluation of those with neural tube defects. Recognition of possible associated heterotopia is important for planning proper treatment and genetic counseling.

Partial Trisomy of 7q: Case Report and Literature Review

This case describes a boy with pure partial trisomy of the long arm of chromosome 7. The only prenatal finding on the boy was cerebral ventricular enlargement. After birth, mild facial dysmorphic features and cardiac malformations (pulmonary valve dysplasia, interatrial and interventricular septal defects) were detected. The boy developed severe psychomotor retardation, failure to thrive, and poor interaction with the environment. Focal seizures occurred in the neonatal period. Left frontotemporal abnormalities were observed in the subsequent electroencephalograms. An area of subependymal nodular heterotopia in the right frontal region was detected. Eighteen cases of 7q pure trisomy have been described in the literature over the years. The present study confirms that, in 7q trisomy cases, there are several common, yet nonspecific, features: macrocephaly, frontal bossing, failure to thrive, psychomotor delay, low-set ears, short neck, and genital-urinary tract abnormalities. Shortened life span seems associated only with duplication of the entire arm, and correlation phenotype-genotype seems questionable.

Subependymal nodular heterotopia

29-year-old woman complained of episodic dizziness with a feeling of unsteadiness. She was referred to the ear, nose and throat clinic. Examination was normal and a pure tone audiogram was within normal limits. Although her symptoms improved with vestibular rehabilitation exercises, they did not resolve entirely and so magnetic resonance (MR) imaging of the brain was requested. Imaging changes (Figure 1a) prompted an urgent referral to the neurology clinic. In her past medical history, the patient had developed seizures at the age of 5 years, initially brief ‘absences’ (eye blinking, head nodding, mouth twitching) with very occasional generalized tonic-clonic seizures. She was the product of a normal full-term vaginal delivery, with normal developmental milestones. There was no family history of seizure disorder. Formal testing at the age of 7 years showed that she was of average intellectual ability and above average ability on the arithmetic subtest. An electroencephalogram showed right temporal slow and sharp wave features. A diagnosis of ‘idiopathic’ temporal lobe epilepsy was made and she was commenced on carbamazepine with reduction in seizure frequency. A computed tomography brain scan performed at the age of 13 years after a further generalized seizure was reported to show a large cerebellar cistern but was otherwise normal. Family history was negative for seizure disorder. Her neurological examination was normal. MR brain imaging (Figure 1b) showed multiple bilateral subependymal nodules of grey matter, lining both lateral ventricles, appearances diagnostic of subependymal nodular heterotopia. No other cerebral or cortical malformation was seen.

Neuronal apoptosis and gray matter heterotopia in microcephaly produced by cytosine arabinoside in mice

Primary microcephaly can be accompanied by numerous migration anomalies. This experiment was undertaken to examine the pathogenesis of gray matter heterotopia and microcephaly that is produced after administering cytosine arabinoside (Ara-C) to mice. Pregnant mice were intraperitoneally injected with Ara-C at 30 mg/kg body weight on days 13.5 and 14.5 of gestation, and then their offspring were examined. On embryonic day 15.5, in the ventricular zone of the cingulate cortex, the neuroepithelial cells lacked BrdU immunoreactivity. Nestin-immunoreactive radial glial fibers and calretinin-positive subplate fibers were disrupted. TUNEL reaction was remarkable throughout the cerebral hemisphere. Subcortical heterotopia in the cingulate cortex and subependymal nodular heterotopia in the dorsolateral part of the lateral ventricles became detectable by the first day after birth. Thirty-two days after birth, microcephaly was apparent; subcortical heterotopia was observed to have increased in size while it was still located in the frontal and cingulate cortices. This experiment demonstrated that Ara-C induces neuronal apoptosis throughout the cerebral hemisphere. The immunohistochemical characteristics in the gray matter heterotopia suggest that both the subcortical and the subependymal heterotopias were formed by neurons originally committed to the neocortex. We conclude that the gray matter heterotopia that accompanies the microcephaly was produced by a disturbance of radial, tangential, and interkinetic neuronal migrations due to the toxicity of Ara-C in the immature developing brain.

Subependymal nodular heterotopia in patients with encephalocele.

Only incidental mention has been made to date of the combined occurrence of subependymal heterotopia and posterior encephalocele. We evaluated the presence of disseminated nodular subependymal heterotopia in two series of patients with posterior encephalocele. The first series consisted of all six patients who were treated in our hospital for encephalocele during the last 11 years and who underwent magnetic resonance imaging (MRI). In three, subependymal nodular heterotopia was found by MRI. The second series consisted of eight autopsy cases with encephalocele, representing all cases of encephalocele that came to autopsy during a 10-year period on whom full microscopic examination could be performed. Nodular heterotopia was found in four. The combined occurrence of these two rare conditions may not be accidental.

Epilepsy Outcome in Periventricular Nodular Heterotopia

The clinical, electroencephalographic, and neuroimaging features and course of seizures in 16 patients with periventricular (subependymal) nodular heterotopia (PNH) were investigated at the University of Bologna, Italy.

Septo-optic dysplasia plus

A 20-year-old man, with a history of congenital nistagmus and mild global developmental delay, presented with four left clonic seizures, which had each lasted for several minutes. A neuro-ophthalmic examination revealed a pendular nistagmus—attenuated with the gaze in the primary position—as well as hypoplasia in both optic discs and amblyopia. We could not observe the septum pellucidum on coronal MRI but saw right frontal subependymal nodular heterotopia (figure). We started treatment with valproic acid and the seizures did not recur. Septo-optic dysplasia (SOD) is a developmental malformation reported by De Morsier that includes dysgenesis of the septum pellucidum, optic nerve hypoplasia, and other cerebral malformations. It is thought of a disorder of midline prosencephalic development. The symptoms, which occur especially when a disorder of cortical development is also present (SOD plus), consist of visual defects, endocrinological manifestations, developmental delay, motor deficits, and epileptic seizures. 1 SOD plus is most frequently associated with schizencephalia, which is now recognised in the current classification of malformations of cortical development, 2 as a differentiated syndrome called schizencephalia septooptic dysplasia. SOD-plus is currently thought to be a genetic disorder that affects multiple stages of cortical development, as opposed to the classical vascular theory based on its association with schizencephalia. Two cases of SOD plus associated with polymicrogyria have recently been published.

Flumazenil Binding and Cortical Malformations

Central Benzodiazepine Receptors in Malformations of Cortical Development: A Quantitative StudyHammers A, Koepp MJ, Richardson MP, Labbe C, Brooks DJ, Cunningham VJ, Duncan JBrain 2001;124:1555–1565PurposeWe calculated [11C]flumazenil volume of distribution ([11C]FMZ-Vd] after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the γ-aminobutyric acid (GABAA)-central benzodiazepine receptor complex.MethodsAbnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomic template for correction for partial volume effect.ResultsNine of 10 patients showed single or multiple increases or decreases in [11C]FMZ-Vd in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [11C]FMZ-Vd than the overlying cortex, which was normal. Decreases i...

Flumazenil Binding and Cortical Malformations.

Central Benzodiazepine Receptors in Malformations of Cortical Development: A Quantitative Study Hammers A, Koepp MJ, Richardson MP, Labbe C, Brooks DJ, Cunningham VJ, Duncan J Brain 2001;124:1555–1565 Purpose We calculated [11C]flumazenil volume of distribution ([11C]FMZ-Vd] after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the γ-aminobutyric acid (GABAA)-central benzodiazepine receptor complex. Methods Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomic template for correction for partial volume effect. Results Nine of 10 patients showed single or multiple increases or decreases in [11C]FMZ-Vd in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [11C]FMZ-Vd than the overlying cortex, which was normal. Decreases in [11C]FMZ-Vd were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [11C]FMZ-Vd in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [11C]FMZ-Vd was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Conclusions Flumazenil binding was decreased in some MCDs with increased grey-matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond magnetic resonance imaging (MRI)-detectable structural changes.

Central benzodiazepine receptors in malformations of cortical development: A quantitative study.

We calculated [(11)C]flumazenil volume of distribution ([(11)C]FMZ-V(d)) after correction for partial volume effect in 10 patients with malformations of cortical development (MCDs) and partial seizures, to quantify the GABA(A)-central benzodiazepine receptor complex. Abnormal grey matter and adjacent or overlying cortex were outlined individually and added to an individualized anatomical template for correction for partial volume effect. Nine of 10 patients showed single or multiple increases or decreases in [(11)C]FMZ-V(d) in or around MCDs. Two of three patients with band heterotopia showed multiple increases in the overlying cortex. In three of four patients with subependymal nodular heterotopia, nodules had lower [(11)C]FMZ-V(d) than the overlying cortex, which was normal. Decreases in [(11)C]FMZ-V(d) were found in two of three clefts and one of six adjacent regions in one schizencephalic patient; another had normal [(11)C]FMZ-V(d) in the thickened cortex itself but increases in all adjacent regions. Binding was reduced within focal cortical dysplasia but increased in adjacent cortex. [(11)C]FMZ-V(d) was normal within one patient's polymicrogyric cortex but increased in one of six adjacent volumes of interest. The localization of abnormalities correlated with EEG and clinical data in cortical MCDs. Flumazenil binding was decreased in some MCDs with increased grey matter volume and increased in some adjacent or overlying areas of normal-appearing cortex, suggesting functional abnormalities beyond MRI- detectable structural changes.

Subependymal nodular heterotopia in patients with encephalocele

Only incidental mention has been made to date of the combined occurrence of subependymal heterotopia and posterior encephalocele. We evaluated the presence of disseminated nodular subependymal heterotopia in two series of patients with posterior encephalocele. The first series consisted of all six patients who were treated in our hospital for encephalocele during the last 11 years and who underwent magnetic resonance imaging (MRI). In three, subependymal nodular heterotopia was found by MRI. The second series consisted of eight autopsy cases with encephalocele, representing all cases of encephalocele that came to autopsy during a 10-year period on whom full microscopic examination could be performed. Nodular heterotopia was found in four. The combined occurrence of these two rare conditions may not be accidental.

Subependymal nodular heterotopia in patients with encephalocele

Only incidental mention has been made to date of the combined occurrence of subependymal heterotopia and posterior encephalocele. We evaluated the presence of dissminated nodular subependymal heterotopia in two series of patients with posterior encephalocele. The first series consisted of all six patients who were treated in our hospital for encephalocele during the last 11 years and who underwent magnetic resonance imaging (MRI). In three, subependymal nodular heterotopia was found by MRI. The second series consisted of eight autopsy cases with encephalocele, representing all cases of encephalocele that came to autopsy during a 10-year period on whom full microscopic examination could be performed. Nodular heterotopia was found in four. The combined occurrence of these two rare conditions may not be accidental.