Nodular Heterotopia Research Articles

Genetic causes underlying grey matter heterotopia.

Grey matter heterotopia (GMH) can cause of seizures and are associated with a wide range of neurodevelopmental disorders and syndromes. They are caused by a failure of neuronal migration during fetal development, leading to clusters of neurons that have not reached their final destination in the cerebral cortex. We have performed an extensive literature search in Pubmed, OMIM, and Google scholar and provide an overview of known genetic associations with periventricular nodular heterotopia (PNVH), subcortical band heterotopia (SBH) and other subcortical heterotopia (SUBH). We classified the heterotopias as PVNH, SBH, SUBH or other and collected the genetic information, frequency, imaging features and salient features in tables for every subtype of heterotopia. This resulted in 105 PVNH, 16 SBH and 25 SUBH gene/locus associations, making a total of 146 genes and chromosomal loci. Our study emphasizes the extreme genetic heterogeneity underlying GMH. It will aid the clinician in establishing an differential diagnosis and eventually a molecular diagnosis in GMH patients. A diagnosis enables proper counseling of prognosis and recurrence risks, and enables individualized patient management.

Magnetic Resonance-Guided Laser Interstitial Thermal Therapy (MR-gLiTT) in Pediatric Epilepsy Surgery: State of the Art and Presentation of Giannina Gaslini Children's Hospital (Genoa, Italy) Series.

Magnetic resonance-guided laser interstitial thermal therapy (MR-gLiTT) is a novel minimally invasive treatment approach for drug-resistant focal epilepsy and brain tumors. Using thermal ablation induced by a laser diode implanted intracranially in a stereotactic manner, the technique is highly effective and safe, reducing the risk associated with more traditional open surgical approaches that could lead to increased neurological morbidity. Indications for MR-gLiTT in pediatric epilepsy surgery include hypothalamic hamartoma, tuberous sclerosis complex, cavernoma-related epilepsy, SEEG-guided seizure onset zone ablation, corpus callosotomy, periventricular nodular heterotopia, mesial temporal lobe epilepsy, and insular epilepsy. We review the available literature on the topic and present our series of patients with drug-resistant epilepsy treated by MR-gLiTT. Our experience, represented by six cases of hypothalamic hamartomas, one case of tuberous sclerosis, and one case of dysembryoplastic neuroepithelial tumor, helps to confirm that MR-gLiTT is a highly safe and effective procedure for several epilepsy conditions in children.

Posterior Quadrant Disconnection for Childhood Onset Sub-Hemispheric Posterior Head Region Epilepsy: Indications in an Indian Cohort and Outcome

Background: Posterior quadrant disconnection (PQD) is an under-utilized surgical technique in the management of refractory epilepsy. There is a dearth of data pertinent to post-PQD seizure outcomes. Methods: This retrospective study analyzed patients with drug-resistant childhood-onset epilepsy who underwent PQD at our center from 2009 to 2018. The clinical, imaging, and electrophysiological data were reviewed. The seizure outcome was noted from the latest follow-up in all patients. Results: Fifteen patients underwent PQD, with a mean age at onset of epilepsy of 3.3 ± 4.6 years. All patients had seizure onset in childhood with focal onset of seizures, and in addition, 5 had multiple seizure types. All cases underwent presurgical workup with MRI, video-EEG, psychometry, while PET/MEG was done if required. Engel Ia and ILAE I outcomes were considered to be favorable. The histology of the specimen showed 9 patients (60%) had gliosis, 4 (26.7%) had focal cortical dysplasia (FCD), while 1 patient had nodular heterotopia and another had polymicrogyria-pachygyria complex. Postoperative follow-up was available in 14 cases. One patient was lost to follow-up. Mean follow-up duration for the cohort was 45 + 24 months. At last, follow-up (n = 14), 66.7% (10 cases) had favorable outcome (Engel Ia). At the end of 1-year follow-up, up to 73% (n = 11) of the patients were seizure-free. Four patients developed transient hemiparesis after surgery which improved completely by 3–6 months. Conclusions: Gliosis was more common etiology requiring PQD in our series than Western series, where FCD was more common. PQD is a safe and effective surgical modality in childhood-onset epilepsy with posterior head region epileptogenic focus.

Bipolar disorder with Melnick\u2013Needles syndrome and periventricular nodular heterotopia: two case reports\xa0and\xa0a review of the\xa0literature

BackgroundMelnick–Needles syndrome and periventricular nodular heterotopia are two usually mutually exclusive phenotypes of F-actin-binding cytoskeletal phosphoprotein Filamin-A mutations. Melnick–Needles syndrome is a rare X-linked condition that is lethal in males and shows great phenotypic variability in affected females. It is caused by mutations in Filamin-A gene, which encodes the protein Filamin A. Defects of the human Filamin-A gene also cause X-linked periventricular nodular heterotopia, a malformation of neuronal migration characterized by nodules of neurons in inappropriate location adjacent to the walls of the lateral ventricles.Case presentationWe report on two Caucasian adolescent females, sisters, diagnosed with Melnick–Needles syndrome and bilateral periventricular nodular heterotopia, who developed bipolar disorder and somatic symptoms disorder at a young age. We also present a review of the literature about mental disorders associated with periventricular nodular heterotopia. Our report shows that patients presenting with atypical and heterogeneous psychiatric disease may have an underrecognized anatomical brain abnormality on genetic basis.ConclusionsWe found records of psychiatric disorders associated with periventricular nodular heterotopia; nevertheless, this is the first report of bipolar disorder occurring in individuals with periventricular nodular heterotopia, and the first report of any psychiatric disorder in individuals affected by Melnick–Needles syndrome. In conclusion, this case report may contribute to characterizing the phenotype of this very rare syndrome.

\u201cWithin a minute\u201d detection of focal cortical dysplasia

PurposeTo evaluate a MRI postprocessing tool for the enhanced and rapid detection of focal cortical dysplasia (FCD).MethodsMP2RAGE sequences of 40 consecutive, so far MRI-negative patients and of 32 healthy controls were morphometrically analyzed to highlight typical FCD features. The resulting morphometric maps served as input for an artificial neural network generating a FCD probability map. The FCD probability map was inversely normalized, co-registered to the MPRAGE2 sequence, and re-transferred into the PACS system. Co-registered images were scrolled through “within a minute” to determine whether a FCD was present or not.ResultsFifteen FCD, three subcortical band heterotopias (SBH), and one periventricular nodular heterotopia were identified. Of those, four FCD and one SBH were only detected by MRI postprocessing while one FCD and one focal polymicrogryia were missed, respectively. False-positive results occurred in 21 patients and 22 healthy controls. However, true positive cluster volumes were significantly larger than volumes of false-positive clusters (p < 0.001). The area under the curve of the receiver operating curve was 0.851 with a cut-off volume of 0.05 ml best indicating a FCD.ConclusionAutomated MRI postprocessing and presentation of co-registered output maps in the PACS allowed for rapid (i.e., “within a minute”) identification of FCDs in our clinical setting. The presence of false-positive findings currently requires a careful comparison of postprocessing results with conventional MR images but may be reduced in the future using a neural network better adapted to MP2RAGE images.

Heterotopia in Individuals with 22q11.2 Deletion Syndrome.

MR imaging studies and neuropathologic findings in individuals with 22q11.2 deletion syndrome show anomalous early brain development. We aimed to retrospectively evaluate cerebral abnormalities, focusing on gray matter heterotopia, and to correlate these with subjects' neuropsychiatric impairments. Three raters assessed gray matter heterotopia and other morphologic brain abnormalities on 3D T1WI and T2*WI in 75 individuals with 22q11.2 deletion syndrome (27 females, 15.5 [SD, 7.4] years of age) and 53 controls (24 females, 12.6 [SD, 4.7] years of age). We examined the association among the groups' most frequent morphologic findings, general cognitive performance, and comorbid neuropsychiatric conditions. Heterotopia in the white matter were the most frequent finding in individuals with 22q11.2 deletion syndrome (n = 29; controls, n = 0; between-group difference, P < .001), followed by cavum septi pellucidi and/or vergae (n = 20; controls, n = 0; P < .001), periventricular cysts (n = 10; controls, n = 0; P = .007), periventricular nodular heterotopia (n = 10; controls, n = 0; P = .007), and polymicrogyria (n = 3; controls, n = 0; P = .3). However, individuals with these morphologic brain abnormalities did not differ significantly from those without them in terms of general cognitive functioning and psychiatric comorbidities. Taken together, our findings, periventricular nodular heterotopia or heterotopia in the white matter (possibly related to interrupted Arc cells migration), persistent cavum septi pellucidi and/or vergae, and formation of periventricular cysts, give clues to the brain development disorder induced by the 22q11.2 deletion syndrome. There was no evidence that these morphologic findings were associated with differences in psychiatric or cognitive presentation of the 22q11.2 deletion syndrome.

Nodular heterotopia: a rare finding in patients with epilepsy and SCN1A mutation.

A 25-year-old man had started febrile seizures from 6 months of age and developed important neurodevelopmental delay. At four years presented with status epilepticus and sequentially with refractory epilepsy. He presents with motor delay, behavior disorder and absent expressive language. Brain MRI showed periventricular nodular heterotopias (Figures and ). The Next Generation Sequencing (NGS) came with a rare frameshift mutation in heterozygosis for SCN1A gene. The presence of periventricular heterotopias in association with SCN1A mutation is rare¹. In literature, we [...]

Does the Modified Arrhenius Model Reliably Predict Area of Tissue Ablation After Magnetic Resonance-Guided Laser Interstitial Thermal Therapy for Pediatric Lesional Epilepsy?

Commercial magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) systems utilize a generalized Arrhenius model to estimate the area of tissue damage based on the power and time of ablation. However, the reliability of these estimates in Vivo remains unclear. To determine the accuracy and precision of the thermal damage estimate (TDE) calculated by commercially available MRgLITT systems using the generalized Arrhenius model. A single-center retrospective review of pediatric patients undergoing MRgLITT for lesional epilepsy was performed. The area of each lesion was measured on both TDE and intraoperative postablation, postcontrast T1 magnetic resonance images using ImageJ. Lesions requiring multiple ablations were excluded. The strength of the correlation between TDE and postlesioning measurements was assessed via linear regression. A total of 32 lesions were identified in 19 patients. After exclusion, 13 pairs were available for analysis. Linear regression demonstrated a strong correlation between estimated and actual ablation areas (R2=.97, P<.00001). The TDE underestimated the area of ablation by an average of 3.92% overall (standard error (SE)=4.57%), but this varied depending on the type of pathologic tissue involved. TDE accuracy and precision were highest in tubers (n=3), with average underestimation of 2.33% (SE=0.33%). TDE underestimated the lesioning of the single hypothalamic hamartoma in our series by 52%. In periventricular nodular heterotopias, TDE overestimated ablation areas by an average of 13% (n=2). TDE reliability is variably consistent across tissue types, particularly in smaller or periventricular lesions. Further investigation is needed to understand the accuracy of this emerging minimally invasive technique.

Frontonasal encephalocele with subependymal heterotopias and cerebellar dysplasia: a rare case report with review of literature

BackgroundEncephaloceles are herniation of brain parenchyma through the defect in the dura and the skull bones. This case report reveals a rare association of frontonasal encephalocele, subependymal nodular heterotopias and cerebellar dysplasia with review of literature.Case presentationFrontonasal encephalocele is a rare entity. We report an 18-months-old male child who presented to the department of pediatrics with chief complaint of congenital swelling in the region of forehead. Swelling was increasing in size as told by the parents of the child. The child was born full term with normal vaginal delivery. There was no history of any obstetrical complications. The swelling was soft, transilluminant and pulsatile in nature. He was referred to the department of radio diagnosis for imaging evaluation. His CT and MRI images revealed defect in the anterior cranial fossa with herniation of meninges and brain parenchyma through it. There was also evidence of subependymal nodular heterotopias in this patient along with hypoplasia of left cerebellar hemisphere and left middle cerebellar peduncle with left cerebellar dysplasia.ConclusionsThis case report describes the coexistence of frontonasal encephaloceles, subependymal nodular heterotopias and cerebellar dysplasia, which is a very rare association.

Factors influencing the detection of treatable epileptogenic lesions on MRI. A randomized prospective study

BackgroundTo prospectively analyze factors associated with detecting epileptogenic lesions on MRI within the work-sharing process of neurologists, epileptologists, radiologists and neuroradiologists.MethodsWe assembled four sets of six MRI scans, each set representing five typical epileptogenic lesions (hippocampal sclerosis or limbic encephalitis; focal cortical dysplasias; periventricular nodular or other heterotopias; long-term epilepsy associated tumors; gliotic scar, hemosiderin or cavernoma), and non - lesional epilepsy.At professional conferences, we invited neurologists, epileptologists, radiologists, and neuroradiologists to read two out of four MRI sets, one of which was presented with a clinical focus hypothesis. Participants were randomly assigned to MRI sets. Effects of examiners’ specialty, duration of training and professional experience on detection rate of epileptogenic lesions were investigated.ResultsFourty-eight neurologists, 22 epileptologists, 20 radiologists and 21 neuroradiologists read 1323 MRI scans. Overall, 613 of 1101 (55.7%) epileptogenic lesions were detected. Long-term epilepsy associated tumors (182/221, 82.4%) were found more frequently than gliotic scar, hemosiderin or cavernoma (157/220, 71.4%), hippocampal sclerosis or limbic encephalitis (141/220, 64.1%), nodular heterotopia (68/220, 30.9%) and focal cortical dysplasias (65/220, 29.5%, p < 0.001). Provision of a focus hypothesis improved the detection of hippocampal sclerosis or limbic encephalitis (86/110, 78.2% vs 55/110, 50%, p < 0.001) and focal cortical dysplasias (40/110, 36.4% vs 25/110, 22.7%, p = 0.037). Neuroradiologists and epileptologists were more likely than radiologists and neurologists to be amongst the most successful readers. In multivariable analysis, type of epileptogenic lesion, specialty of MRI reader, and provision of focus hypothesis predicted correct identification of epileptogenic lesions.ConclusionsEpileptogenic lesions are often not recognized on MRI even by expert readers. Their detection can be improved by providing a focus hypothesis. These results stress the need for training in the MRI characteristics of epilepsy - specific pathology, and, most importantly, interdisciplinary communication between neurologists/epileptologists and (neuro)radiologists to improve detection of epileptogenic lesions.

New variants in FLNA gene cause periventricular nodular heterotopia and epileptic seizure in three cases

To explore the genetic bases of 3 patients with periventricular nodular heterotopia and epileptic seizure. The clinical data of three patients presenting with periventricular nodular ectopic with epileptic seizure were analyzed. Whole exome sequencing (WES) was performed on the patients, and Sanger sequencing was used to validate the suspected variants. In three female patients, head MRI showed nodular gray matter ectopic in the bilateral ventricle. WES identified the heterozygous c.2720del T(p.Leu907Argfs*39) variant of FLNA gene in case 1 and her mother (case 2), and heterozygous c.1387_1390del GTGC(p.Val463Profs*34) of FLNA gene in case 3. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC (p.Val463Profs*34) variants of FLNA gene were predicted to be pathogenic (PVS1+PM2+PP1) and likely pathogenic(PVS1+PM2), respectively. The c.2720delT(p.Leu907Argfs*39) and c.1387_1390del GTGC(p.Val463Profs*34) variants of FLNA gene may be the genetic cause of the three patients.

Further evidence for de novo variants in SYNCRIP as the cause of a neurodevelopmental disorder.

SYNCRIP encodes for the Synaptotagmin-binding cytoplasmic RNA-interacting protein, involved in RNA-binding and regulation of multiple cellular pathways. It has been proposed as a candidate gene for neurodevelopmental disorders (NDDs) with autism spectrum disorder (ASD), intellectual disability (ID), and epilepsy. We ascertained genetic, clinical, and neuroradiological data of three additional individuals with novel de novo SYNCRIP variants. All individuals had ID. Autistic features were observed in two. One individual showed myoclonic-atonic epilepsy. Neuroradiological features comprised periventricular nodular heterotopia and widening of subarachnoid spaces. Two frameshift variants in the more severely affected individuals, likely result in haploinsufficiency. The third missense variant lies in the conserved RNA recognition motif (RRM) 2 domain likely affecting RNA-binding. Our findings support the importance of RRM domains for SYNCRIP functionality and suggest genotype-phenotype correlations. Our study provides further evidence for a SYNCRIP-associated NDD characterized by ID and ASD sporadically accompanied by malformations of cortical development and myoclonic-atonic epilepsy.

Diseases associated with mutations in the filamin A gene (FLNA)

The article presents literature review of the diseases associated with mutations in the FLNA gene encoding filamin A, which is a cytoskeleton protein with polymorphic functions. The mutations of this gene lead to the damage of the central nervous system (periventricular nodular heterotopy), respiratory organs (emphysema, interstitial lung disease), heart (congenital heart defects and minor heart abnormalities); the listed diseases can be diagnosed at different ages. The information presented in this review can be useful for clinical geneticists, specialists in rare (orphan) diseases, pediatricians, neonatologists, neurologists, epileptologists, pulmonologists, surgeons, cardiologists for timely diagnosis and improvement of medical care for patients requiring a multidisciplinary approach.

Convolutional neural networks to identify malformations of cortical development: A feasibility study

ObjectiveTo develop and test a deep learning model to automatically detect malformations of cortical development (MCD). Methods: We trained a deep learning model to distinguish between diffuse cortical malformation (CM), periventricular nodular heterotopia (PVNH), and normal magnetic resonance imaging (MRI). We trained 4 different convolutional neural network (CNN) architectures. We used batch normalization, global average pooling, dropout layers, transfer learning, and data augmentation to minimize overfitting. ResultsThere were 45 subjects (866 images) with a normal MRI, 52 subjects (790 images) with CM, and 32 subjects (750 images) with PVNH. There was no subject overlap between the training, validation, and test sets. The InceptionResNetV2 architecture performed best in the validation set in all models and was evaluated in the test set with the following results: 1) the model distinguishing between CM and normal MRI yielded an area under the curve (AUC) of 0.89 and accuracy of 0.81; 2) the model distinguishing between PVNH and normal MRI yielded an AUC of 0.90 and accuracy of 0.84; 3) the model distinguishing between the three classes (CM, PVNH, and normal MRI) yielded an AUC of 0.88 and accuracy of 0.74. Visualization with gradient-weighted class activation maps and saliency maps showed that the deep learning models classified images based on relevant areas within each image. SignificanceThis study showed that CNNs can detect MCD at a clinically useful performance level with a fully automated workflow without image feature selection.

The clinical and imaging features of FLNA positive and negative periventricular nodular heterotopia

BackgroundPeriventricular nodular heterotopia (PVNH) is caused by abnormal neuronal migration, resulting in the neurons accumulate as nodules along the surface of the lateral ventricles. PVNH often cause epilepsy, psychomotor development or cognition problem. Mutations in FLNA (Filamin A) is the most common underlying genetic etiology. Our purpose is to delineate the clinical and imaging spectrum that differentiates FLNA-positive and FLNA-negative PVNH patients. MethodsWe included 21 patients with confirmed PVNH. The detailed clinical information, electroencephalography, and other clinical findings were recorded. Detailed brain MR imaging was assessed. Mutation analysis of the FLNA gene was used Sanger sequencing or a next generation sequencing based assay. ResultsFLNA mutations were identified in 9 patients (7 females and 2 males), including two nonsense, two splice site, three frameshift, and two missense mutations. In FLNA-positive group, 8 patients had anterior predominant bilateral symmetric presentation and only one had asymmetrical distribution and dilated ventricles. Extra-cerebral features were more often observed in FLNA-positive group than FLNA-negative group. ConclusionGenetics of PVNH is heterogenous, and mutations in FLNA gene account for less than half of the patients in our cohort. Our finding between FLNA-positive and FLNA-negative patients could guide the clinicians to select relevant genetic testing.

Epileptic children with hemispheres’ asymmetry. Quantitative brain magnetic resonance-based analysis of apparently unaffected hemisphere. Case-control study

ObjectiveWe performed a quantitative hemispheres analysis in epileptic children with hemispheres’ asymmetry -due to unilateral dysplastic malformation- in order to recognize subtle volumetric changes of the contralateral and apparently unaffected hemisphere. Methods13 children with Hemimegalencephaly (HME) and 20 with Hemimicrencephaly (Hme) were clustered in subgroups according to underlying hemispheric cortical dysplastic malformation and epilepsy pattern. 3D FSPGR T1weighted images were used to assess white and grey matter volumes for both hemispheres. Each volumetric parameter was compared with the average of an age-matched healthy control group. ResultsHME subgroups: HME with pachygyria and focal (HME-PG-F; n 6) or multifocal epilepsy (HME-PG-MF; n.7). In both subgroups affected hemisphere (AH) volume was increased and contralateral hemisphere (CH) showed white matter volume reduction; in HME-PG-MF grey matter volume of CH was more reduced than HME-PG-F.Hme subgroups: Hme with polimicrogyria and focal epilepsy (Hme-PMG-F; n.8), Hme with giant subcortical nodular heterotopia and focal (Hme-SCH-F; n.6) or multifocal epilepsy (Hme-SCH-MF; n.6). In all subgroups AH volume was reduced; the volume of CH was significantly increased in Hme-PMG-F and Hme-SCH-MF while it was not significantly increased in Hme-SCH-F compared to affected hemisphere. ConclusionsIn patients with hemispheres’ asymmetry, quantitative high-resolution MRI offers a more objective assessment of brain structures volume. The type of hemispheric dysplastic malformation together with the age of epilepsy onset and epileptic pattern may contribute to changes in contralateral and apparently unaffected hemisphere. Future studies are warranted to evaluate whether the early identification of these changes might help in planning future antiepileptic treatments.

Stereo-EEG Evaluation and Surgical Treatment in Patients With Drug-Resistant Focal Epilepsy Associated With Nodular Heterotopia.

Nodular heterotopia (NH) is a common cause of drug-resistant epilepsy. Only limited studies detail the treatment of NH with laser interstitial thermal therapy and none analyze the relation between epileptogenicity and NH location. We retrospectively studied nine patients with drug-resistant epilepsy and NH who underwent stereoelectroencephalography and subsequent epilepsy surgery. Nodular heterotopia in the frontal lobes or along the bodies of the lateral ventricles was classified as anterior NH. Nodular heterotopia in the trigones, temporal or occipital horns, or temporal lobes was classified as posterior NH. Nodular heterotopia in both anterior and posterior locations was classified as diffuse NH. Interictal and ictal stereoelectroencephalography were analyzed, and patients were followed postoperatively to assess outcomes. Of the six patients who underwent nine laser interstitial thermal therapy procedures either in isolation or in combination with other surgical therapies, four patients were Engel Ia, one was Engel IIb, and one was Engel IIIa, with an average follow-up of 22.8 months. All patients with posterior NH had interictal epileptiform abnormalities and seizures originating from the posterior NH. None of the patients with anterior NH had epileptiform activity recorded from their NH. Laser interstitial thermal therapy alone or in combination with other surgical therapies is an effective treatment in those with drug-resistant epilepsy because of NH, even in those with extensive NH and broad seizure onset. We observed a trend suggesting that posterior NH are more likely to be epileptogenic compared with anterior NH and recommend that in patients with anterior NH, alternative epilepsy etiologies and stereoelectroencephalography implantation strategies be considered.

Radiological and Clinical Value of 7T MRI for Evaluating 3T-Visible Lesions in Pharmacoresistant Focal Epilepsies.

Objective: The recent FDA approval of the first 7T MRI scanner for clinical diagnostic use in October 2017 will likely increase the utilization of 7T for epilepsy presurgical evaluation. This study aims at accessing the radiological and clinical value of 7T in patients with pharmacoresistant focal epilepsy and 3T-visible lesions.Methods: Patients with pharmacoresistant focal epilepsy were included if they had a lesion on pre-operative standard-of-care 3T MRI and also a 7T research MRI. An epilepsy protocol was used for the acquisition of the 7T MRI. Prospective visual analysis of 7T MRI was performed by an experienced board-certified neuroradiologist and communicated to the patient management team. The clinical significance of the additional 7T findings was assessed by intracranial EEG (ICEEG) ictal onset, surgical resection, post-operative seizure outcome and histopathology. A subset of lesions were demarked with arrows for subsequent, retrospective comparison between 3T and 7T by 7 neuroradiologists using a set of quantitative scales: lesion presence, conspicuity, boundary, gray-white tissue contrast, artifacts, and the most helpful sequence for diagnosis. Conger's kappa for multiple raters was performed for chance-adjusted agreement statistics.Results: A total of 47 patients were included, with the main pathology types of focal cortical dysplasia (FCD), hippocampal sclerosis, periventricular nodular heterotopia (PVNH), tumor and polymicrogyria (PMG). 7T detected additional smaller lesions in 19% (9/47) of patients, who had extensive abnormalities such as PMG and PVNH; however, these additional findings were not necessarily epileptogenic. 3T−7T comparison by the neuroradiologist team showed that lesion conspicuity and lesion boundary were significantly better at 7T (p < 0.001), particularly for FCD, PVNH and PMG. Chance-adjusted agreement was within the fair range for lesion presence, conspicuity and boundary. Gray-white contrast was significantly improved at 7T (p < 0.001). Significantly more artifacts were encountered at 7T (p < 0.001).Significance: For patients with 3T-visible lesions, 7T MRI may better elucidate the extent of multifocal abnormalities such as PVNH and PMG, providing potential targets to improve ICEEG implantation. Patients with FCD, PVNH and PMG would likely benefit the most from 7T due to improved lesion conspicuity and boundary. Pathologies in the antero–inferior temporal regions likely benefit less due to artifacts.

Periventricular nodular heterotopias an atypical manifestation of Joubert syndrome

Joubert syndrome (JS) is characterized by varying degrees of mid and hindbrain malformations. A thickened superior cerebellar peduncle (“molar tooth sign”), varying degree of cerebellar vermian clefting, and an oddly shaped (“bat-wing”) fourth ventricle are essential diagnostic cues on imaging. When JS is associated with renal, ocular, hepatobiliary, or oro-facial abnormalities, the term Joubert syndrome and related disorders (JSRD) is used.&#x0D; We report a classic case of this rare disease in a 5 month old male child who presented to our department for assessment of developmental delay. MRI revealed molar-tooth appearance of midbrain, an abnormally shaped fourth ventricle, and vermian aplasia. Additional findings present in our case were corpus callosum dysgenesis, colpocephaly, generalized cortical atrophy, and periventricular nodular heterotopia. Subsequently, an ultrasound of the abdomen was performed to look for any associated anomalies. It revealed diffuse bilateral echogenic kidneys with attenuated corticomedullary differentiation (likely due to micro cysts in medulla) and few thin-walled peripheral renal cortical cysts.&#x0D; Callosal dysgenesis, colpocephaly, cortical atrophy and cortical heterotopias are less common manifestations of JS/JSRD and periventricular nodular heterotopia has been infrequently reported in cases of Joubert syndrome.&#x0D; Key-words: Joubert Syndrome, MRI, Molar Tooth Sign, Periventricular Nodular Heterotopia, Bilateral Echogenic Kidneys

Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

BackgroundPeriventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH.Case presentationWe report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus.ConclusionWe hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.