CDKL5 deficiency disorder: progressive brain atrophy may be part of the syndrome.

The clinical phenotype of Cyclin-Dependent Kinase-Like 5 (CDKL5) deficiency disorder (CDD) has been delineated but neuroimaging features have not been systematically analyzed. We studied brain magnetic resonance imaging (MRI) scans in a cohort of CDD patients and reviewed age at seizure onset, seizure semiology, head circumference. Thirty-five brain MRI from 22 unrelated patients were included. The median age at study entry was 13.4 years. In 14/22 patients (85.7%), MRI in the first year of life was unremarkable in all but two. In 11/22, we performed MRI after 24 months of age (range 2.5-23 years). In 8 out of 11 (72.7%), MRI showed supratentorial atrophy and in six cerebellar atrophy. Quantitative analysis detected volumetric reduction of the whole brain (-17.7%, P-value = 0.014), including both white matter (-25.7%, P-value = 0.005) and cortical gray matter (-9.1%, P-value = 0.098), with a reduction of surface area (-18.0%, P-value = 0.032), mainly involving the temporal regions, correlated with the head circumference (ρ = 0.79, P-value = 0.109). Both the qualitative structural assessment and the quantitative analysis detected brain volume reduction involving the gray and white matter. These neuroimaging findings may be related to either progressive changes due to CDD pathogenesis, or to the extreme severity of epilepsy, or both. Larger prospective studies are needed to clarify the bases for the structural changes we observed.

Spinal cord involvement and paroxysmal events in "Infantile Onset Transient Hypomyelination" due to TMEM63A mutation.

Monoallelic mutations on TMEM63A have been recently reported as cause of a previously unrecognized disorder named "infantile-onset transient hypomyelination". Clinical and neuroradiological presentation is described as highly similar to Pelizaeus-Merzbacher Disease but evolution over time was surprisingly benign with a progressive spontaneous improving course. We report on a new TMEM63A-mutated girl. The clinical picture was similar to the one already described except for the presence of recurrent episodes of unilateral eyelid twitching, and for the evidence of spinal cord involvement on MRI. These are interesting findings helping in distinguishing this condition from classic PMD since early disease stages. However, additional observations are needed to confirm if these are common features of this condition.

Magnetic resonance features and cranial nerve involvement in pediatric head and neck rhabdomyosarcomas.

PURPOSE: Rhabdomyosarcoma (RMS) is a malignant tumor frequent in children. The frequency and characteristics of cranial nerve involvement in pediatric head and neck (H&N) RMS have been scarcely reported. The aim of this study is to review a large cohort of pediatric head and neck RMS with an emphasis on cranial nerve involvement. METHODS: We retrospectively reviewed H&N RMS cases from 3 tertiary hospitals over a 10-year period. Cranial nerve involvement was defined as radiologically apparent tumor extension along a nerve and/or the presence of secondary signs. Scans were reviewed by two pediatric neuroradiologists, blinded to clinical data. RESULTS: A total of 52 patients met the inclusion criteria. Histologically, 39/52 were embryonal RMS, while 13/52 were alveolar RMS. Regional lymph nodes metastases were present in 19.2%. Cranial nerve involvement was present in 36.5%. Nerves were mainly involved as a direct extension of the mass through skull base foramina or after invasion of cavernous sinus, Meckel's cave, orbital apex, or stylomastoid foramen. CONCLUSION: Cranial nerve involvement is frequent in pediatric head and neck RMS and occurs secondary to "geographic" invasion due to direct extension through skull base foramina or cavernous sinus. These tumors never showed distant perineural metastatic disease as is seen in cases of adult head and neck carcinomas. This implies a different biological interaction between the nerves and these tumors in comparison to adult H&N tumors.

Cortical formation abnormalities on foetal MR imaging: a proposed classification system trialled on 356 cases from Italian and UK centres.

OBJECTIVE: To formulate a classification system for foetal cortical formation abnormalities (CFAs) based on in utero magnetic resonance (iuMR) appearances and trial it in 356 cases. METHODS: This retrospective study included all cases of foetal CFA diagnosed between 2000 and 2017 from seven centres in Italy and UK. All of the studies were reviewed by a panel of paediatric neuroradiologists experienced in iuMR with the aid of an algorithm designed to categorise the abnormalities. RESULTS: Consensus expert review confirmed 356 foetuses with CFA and the first level of classification distinguished bilateral CFA (229/356-64%) from unilateral CFA (127/356-36%) cases with sub-classification of the bilateral cases into asymmetric (65/356-18%) and symmetric (164/356-46%) involvement. There was a statistically significant excess of foetuses with small head size, e.g. 17% of the cohort had a bi-parietal diameter < 3rd centile. There was a small but statistically significant excess of males in the cohort. Further categorisation was made on fine anatomical structure. CONCLUSIONS: It is often not possible to classify foetal CFA using the principles and nomenclature used in paediatric neuroradiology. We have created a classification system for foetal CFA based on the analysis of 356 cases and believe that this will assist future research designed to correlate ante-natal and post-natal imaging features and understand the clinical sequelae of CFA described in utero. KEY POINTS: • We describe a morphological classification system of foetal brain cortical formation abnormalities that can be used in clinical practice. • This classification system can be used in future research studies to evaluate the long-term imaging and clinical outcomes of foetal brain cortical formation abnormalities in 17- to 38-week gestational age range. • The practical value of the work is in providing a framework and language to look for imaging clues that may differentiate between different CFA in further studies.

Prenatal magnetic resonance imaging within the 26th week of gestation may predict the fate of isolated upward rotation of the cerebellar vermis: insights from a multicentre study.

OBJECTIVES: We investigated whether prenatal magnetic resonance imaging (MRI) within 26 weeks of gestation (GW) may predict the fate of isolated upward rotation of the cerebellar vermis (URCV). METHODS: This retrospective multicentre observational study included foetuses diagnosed with isolated URCV in prenatal MRI performed within 26 GW. Isolated URCV was defined by a brainstem-vermis angle (BVA) ≥ 12° in the MR midline sagittal view without abnormalities of the supratentorial structures, brainstem, or cerebellum hemispheres. The assessments included the BVA, clival-supraoccipital angle, transverse diameter of the posterior cranial fossa, tentorial angle, width of the cisterna magna (WCM), ventricular width, vermian diameters, hypointense stripes, and cerebellar tail sign. Late prenatal or postnatal MRI was used as a reference standard to assess the final vermian fate (rotated/de-rotated). RESULTS: Forty-five foetuses (mean GW at prenatal MRI = 21.5 ± 1.4 weeks) were included. In the reference standard, the vermis was de-rotated in 26 cases (57.7%). At least two of the following criteria were used to predict the persistence of URCV at imaging follow-up: BVA ≥ 23°, WCM ≥ 9 mm, and the cerebellar tail sign. The results were a sensitivity of 84.21% (95% CI, 60.4-96.6%), specificity of 80.8% (95% CI, 60.6-93.4%), positive predictive value of 76% (95% CI, 58.7-87.8%), and negative predictive value of 87.5% (95% CI, 70.9-95.2%). CONCLUSIONS: MRI within 26 GW on foetuses diagnosed with isolated URCV may predict delayed cerebellar vermis de-rotation, which is associated with good neurodevelopmental outcome in most cases. KEY POINTS: • Foetal MRI is a valuable tool in predicting the fate of isolated upward-rotated cerebellar vermis. • A wider angle between the brainstem and vermis is associated with higher risk of persistence of vermian rotation. • The presence of ≥ 2 factors among a brainstem-to-vermis angle ≥ 23°, width of the cisterna magna ≥ 9 mm, and the presence of the "cerebellar tail sign" has a sensitivity of 84.21% (95% CI, 60.4-96.6%) and specificity of 80.8% (95% CI, 60.6-93.4%) in predicting the persistence of the vermian rotation at imaging follow-up.

Neurovascular Perfusion Study With DynaPBV During Preoperative Balloon Test Occlusion: A Feasibility Study on Aneurysm and Tumor Lesions.

To report feasibility, safety, and technical advantages of flat-detector computed tomography perfusion (FD-CTP) during balloon test occlusion (BTO) angiography studies, 10 patients patients scheduled for BTO were evaluated. Cerebral blood volume maps were extracted from FD-CTP images acquired during the test. The FD-CTP perfusion combined with BTO is feasible and safe in intracranial tumor, and aneurysm cases in which vessel sacrifice should be considered.

The spectrum of neuroimaging findings in febrile infection-related epilepsy syndrome (FIRES): A literature review.

Febrile infection-related epilepsy syndrome (FIRES) is a rare severe epileptic syndrome occurring in previously healthy children and characterized by refractory status epilepticus (SE) following a febrile illness. Brain imaging findings in affected patients have been reported in few case series and some case reports. This article is a comprehensive review of the magnetic resonance imaging (MRI) characteristics in all reported patients with a diagnosis of FIRES, describing the findings in the acute and chronic phases of the disease, and discussing possible pathogenesis and radiologic differential diagnoses. Most of the patients had normal brain scans in the acute phase (61%) and about 25% of the patients reported in literature had abnormalities in the temporal lobes. Changes in the basal ganglia and rarely in thalami or brainstem have also been described, as well as diffuse cerebral edema in a minority of patients during the acute phase. The chronic phase of the disease was characterized by atrophic changes and evidence of mesiotemporal sclerosis. An understanding of these MRI abnormalities is necessary to support the diagnosis of FIRES and exclude mimics.

Intrauterine fetal MR versus postmortem MR imaging after therapeutic termination of pregnancy: evaluation of the concordance in the detection of brain abnormalities at early gestational stage.

BACKGROUND AND PURPOSE: Fetal postmortem MR Imaging (pmMRI) has been recently used as an adjuvant tool to conventional brain autopsy after termination of pregnancy (TOP). Our purpose was to compare the diagnostic performance of intrauterine MRI (iuMRI) and pmMRI in the detection of brain anomalies in fetuses at early gestational age (GA). MATERIAL AND METHODS: We retrospectively collected 53 fetuses who had undergone iuMRI and pmMRI for suspected brain anomalies. Two pediatric neuroradiologists reviewed iuMRI and pmMRI examinations separately and then together. We used Cohen's K to assess the agreement between pmMRI and iuMRI. Using the combined evaluation iuMRI+pMRI as the reference standard, we calculated the "correctness ratio." We used Somers' D to assess the cograduation between postmortem image quality and time elapsed after fetus expulsion. RESULTS: Our data showed high agreement between iuMRI and pmMRI considering all the categories together, for both observers (K1 0.84; K2 0.86). The correctness ratio of iuMRI and pmMRI was 79% and 45% respectively. The major disagreements between iuMRI and pmMRI were related to postmortem changes as the collapse of liquoral structures and distorting phenomena. We also found a significant cograduation between the time elapsed from expulsion and pmMRI contrast resolution and distortive phenomena (both p < 0.001). CONCLUSIONS: Our study demonstrates an overall high concordance between iuMRI and pmMRI in detecting fetal brain abnormalities at early GA. Nevertheless, for the correct interpretation of pmMRI, the revision of fetal examination seems to be crucial, in particular when time elapsed from expulsion is longer than 24 h. KEY POINTS: • IuMRI and pmMRI showed overall high concordance in detecting fetal brain abnormalities at early GA. • PmMRI corroborated the antemortem diagnosis and it could be a valid alternative to conventional brain autopsy, only when the latter cannot be performed. • Some caution should be taken in interpreting pmMR images when performed after 24 h from fetal death.

Hypothalamic malformations in patients with X-linked deafness and incomplete partition type 3.

Patients with X-linked deafness carry mutations in the POU3F4 gene and have pathognomonic inner ear malformations characterised by symmetrical incomplete partition type 3 (absent modiolus and lamina spiralis but preserved interscalar septum in a normal-sized cochlea) and large internal auditory meatus (IAM) with an increased risk of gusher during stapes surgery. We describe a range of fairly characteristic malformations in the hypothalamus of some patients with this rare condition, ranging from subtle asymmetric appearance and thickening of the tuber cinereum to more marked hypothalamic enlargement. We discuss the role of POU3F4 in the normal development of both the inner ear and hypothalamus and the proposed pathophysiology of incomplete partition type 3.

Imaging of temporal bone inflammations in children: a pictorial review.

PURPOSE: Understanding the underlying pathophysiology and the patterns of disease spread is crucial in accurate image interpretation. In this pictorial review, the common and important inflammatory processes of the temporal bone in children will be discussed, and key computed tomography (CT) and magnetic resonance imaging (MRI) features described. METHODS: Inflammatory processes are categorized by anatomical location: the petrous apex and the inner, middle and outer ear. A complete review of the literature is provided. RESULTS: Cholesteatoma, cholesterol granuloma and mucoceles are inflammatory processes that occur across the anatomical subsites of the temporal bone, whilst site-specific inflammatory processes include labyrinthitis ossificans in the inner ear and keratosis obturans in the external ear. Infection is a key cause of inflammation in the temporal bone, and specific infections include petrous apicitis, otitis media and necrotizing otitis externa. Finally, important mimics and do-not-touch lesions are considered. CT and MRI are complementary in assessing these disorders, as two of the most important diagnostic clues are the presence of bone erosion, best appreciated on CT, and true diffusion restriction as seen on MRI. Flow charts to assist in the diagnosis of paediatric temporal bone inflammatory disease are also provided. CONCLUSION: Paediatric temporal bone inflammatory processes are common and can have severe clinical sequelae. Timely intervention, facilitated by correct radiological diagnosis, can often prevent progression of disease, loss of hearing and systemic illness.

Volumetric assessment of tumor size changes in pediatric low-grade gliomas: feasibility and comparison with linear measurements.

PURPOSE: We report a retrospective comparison between bi-dimensional RANO criteria and manual volumetric segmentation (MVS) in pediatric low-grade gliomas. METHODS: MRI FLAIR or T1 post contrast images were used for assessment of tumor response. Seventy patients were included in this single center study, for each patient two scans were assessed ("time 0" and "end of therapy") and response to therapy was evaluated for both methods. Inter-reader variability and average time for volumetric assessment were also calculated. RESULTS: Fourteen (20%) of the 70 patients had discordant results in terms of response assessment between the bi-dimensional measurements and MVS. All volumetric response assessments were in keeping with the subjective analysis of tumor (radiology report). Of the 14 patients, 6 had stable disease (SD) on MVS and progressive disease (PD) on 2D assessment, 5 patients had SD on MVS and partial response (PR) on 2D assessment, 2 patients had PD on MVS and SD on 2D assessment, and 1 patient had PR on MVS and SD on 2D analysis. The number of discordant results rises to 21(30%) if minor response is integrated in the response assessment. MVS was relatively fast and showed high inter-reader concordance. CONCLUSION: Our analysis shows that therapeutic response classification may change in a significant number of children by performing a volumetric tumor assessment. Furthermore, MVS is not particularly time consuming and has very good inter-reader concordance.

Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.

A homoallelic missense founder mutation of the iron-sulfur cluster assembly 2 (ISCA2) gene has been recently reported in six cases affected by an autosomal recessive infantile neurodegenerative mitochondrial disorder. We documented a case of a 2-month-old girl presenting with severe hypotonia and nystagmus, who rapidly deteriorated and died at the age of three months. Increased cerebral spinal fluid level of lactate, documented also at the brain spectroscopy, involvement of the cortex, restricted diffusion of white and gray matter abnormalities, sparing of the corpus callosum and extensive involvement of the spinal cord were observed. Her clinical presenting features and course as well as some neuroradiological findings mimicked those of early-onset leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate (LBSL). The analysis of the mitochondrial respiratory chain function showed a reduced activity of complexes II and IV. The girl harboured two heterozygous mutations in the ISCA2 gene. A comprehensive review of the literature and a comparison with the cases of early onset LBSL enabled us to highlight significant differences in the clinical, biochemical and neuroradiological phenotype between the two conditions, which also emerged from the comparison with the other 6 reported cases of ISCA2 gene mutation previously reported. In summary, this represents the second report ever published associating ISCA2 gene mutation with a mitochondrial leukoencephalopathy, with a different genetic mechanism to the previous cases. Molecular analysis of ISCA2 should be included in the genetic panel for the diagnosis of early onset mitochondrial leukoencephalopathies.

Early Prenatal MRI of Cervical "Abortive" Myelocystocele: Case Report and Review of the Literature.

Cervical abortive myelocistocele is a very rare congenital malformation. In this case report, we describe the prenatal magnetic resonance imaging (MRI) of such entity in a 20-week gestational age fetus, whose imaging features showed to be different from the only other previous prenatal report. We underscored the value of fetal MR for counseling and prognosis, especially when assessing the integrity of the spinal cord.

Acute isolated vertigo with vertical up-beating nystagmus: A rare case of nucleus intercalatus of Staderini ischemia.

The role of intercalatus nucleus of Staderini (INS), the most caudal of the perihypoglossal nuclei, is much debated. Last research seems to suggest that this nucleus plays a role as a vertical eyes movements integrator. The few clinical reports present in the literature that describe isolated lesions of the INS have described patients presenting in acute with up-beating vertical spontaneous nystagmus. Isolated acute lesion of INS is, in fact, much rare, and, without other neurological signs, is exceptional. We present a case of acute isolated vertigo with no other neurological signs or symptoms, due to INS ischemia provoked by vertebral artery stenosis. The patient presented with spontaneous vertical up-beating nystagmus that showed at videonystagmographic recording, a clear exponential decay of angular slow-phase velocity, that is considered a typical sign of neural integrator impairment. This case seems to represent a further confirm that INS is part, as a vertical-to-position neural integrator, of the neural circuit controlling the vertical eyes movements.

Neonatal Arterial Ischemic Stroke Secondary to Carotid Artery Dissection: A Case Report and Systematic Literature Review.

BACKGROUND: Carotid artery (CA) dissection is a rare etiology of neonatal arterial ischemic stroke (NAIS). METHODS: We describe one novel case and conduct a systematic literature review on NAIS attributed to CA dissection, to collect data on its clinical-radiological presentation, treatment, and outcome. RESULTS: Eight published cases of NAIS attributed to CA dissection were identified and analyzed with our case. All patients (nine of nine) were born at term, and eight of nine experienced instrumental/traumatic delivery or urgent Caesarean section. None had fetal problems during pregnancy or thrombophilia. Signs and symptoms at presentation (between days of life 0 and 6) included seizures (eight of nine), respiratory distress or irregular breathing (five of nine), hyporeactivity, decreased consciousness or irritability (four of nine), and focal neurological signs (two of nine). At magnetic resonance imaging (MRI), stroke was unilateral in seven of nine and extensive in five of nine. CA dissection was documented by neuroimaging or at postmortem studies (seven of nine), and hypothesized by the treating physicians based on delivery and neuroradiology characteristics (in the remaining two of nine). Antithrombotic treatment was used in two of nine. According to available follow-up, one of eight died at age seven days, seven of eight had neurological/epileptic sequelae, and CA recanalization occurred in three of four. CONCLUSIONS: NAIS attributed to CA dissection is rarely identified in the literature, often preceded by traumatic/instrumental delivery, presenting with seizures and systemic signs/symptoms, and often characterized by extensive MRI lesions and neurological sequelae. Definite evidence and recommendations on antithrombotic treatment are lacking.

Brain fetal neuroradiology: a beginner's guide.

The importance of fetal magnetic resonance imaging (MRI) in the prenatal diagnosis of central nervous system (CNS) anomalies is rapidly increasing. Fetal MRI represents a third level examination usually performed, as early as 18-20 weeks of gestational age, when a second level (expert) neuro-ultrasonography (US) evaluation raises the suspicion of a CNS anomaly or when a genetic disorder is known. Compared to the US, MRI has the advantage to allow a better visualization and characterization of brain structures so to detect anomalies not visible in the US, thus resulting in relevant implications for parent counselling and pregnancy management. Moreover, the improvement of MRI technologies permits to obtain ultrafast sequences, which minimize the drawback of movement artifacts, and to perform advanced studies. This review aims at providing a practical guide for trainees and fellows who are approaching fetal MRI. In the first part, we provide information about indications, safety and protocols based on the state-of-the-art sequences, with a mention on the innovations related to the use of a 3T scanner. The second part is focused on the normal development of the human fetal brain related to its MR appearance, whose knowledge is essential to detect possible abnormalities. The last section briefly describes the most frequent abnormalities in the fetal brain and spine as depicted by MRI.

Exploratory Investigation of Brain MRI Lesions According to Whole Sample and Visual Function Subtyping in Children With Cerebral Visual Impairment.

Background: There is limited research on brain lesions in children with cerebral visual impairment (CVI) of heterogeneous etiologies and according to associated subtyping and vision dysfunctions. This study was part of a larger project establishing data-driven subtypes of childhood CVI according to visual dysfunctions. Currently there is no consensus in relation to assessment, diagnosis and classification of CVI and more information about brain lesions may be of potential diagnostic value. Aim: This study aimed to investigate overall patterns of brain lesions and associations with level of visual dysfunction and to compare the patterns between the classification subgroups in children with CVI. Methods: School-aged children with CVI received ophthalmological and neuro-psychological/developmental assessments to establish CVI-related subtyping. Other pediatric information was collected from medical records. MRI scans were coded according to a semi-quantitative template including brain regions (right hemisphere, left hemisphere, visual pathways) and summed for total scores. Non-parametric analyses were conducted. Results: 28 children had clinical brain MRI scans available [44% of total sample, Group A (lower severity of visual dysfunctions) n = 16, Group B (higher severity) n = 12]. Total brain scores ranged between 0 and 18 (Group A mdn = 7, IQR = 0.8-10.0, Group B mdn = 10, IQR = 6.5-11.8) and were widespread across regions. 71 per cent had post-geniculate visual pathway damage. The median total brain and hemisphere scores of Group B were higher than subgroup A but differences did not reach statistical significance. No statistically significant associations were found between brain scores and vision variables (acuity, contrast sensitivity). Conclusion: This study found a spread of lesions across all regions on the brain scans in children with congenital CVI. The majority had damage in the postgeniculate visual pathways and visual cortex region suggesting this is an area of interest and potentially informative for diagnosis. However the subtyping classification did not show differences in number or region of lesions though the trend was higher toward Group B. This study confirms the complex diffuse and variable nature of brain lesions in children with congenital CVI, many of whom have other neurological impairments.