FLAIR Hyperintense Cortical Lesions in a 4-Year-Old Child with Myelin Oligodendrocyte Glycoprotein (MOG)-Associated Encephalitis and Seizures: A Case Report.

Myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD) is a relatively uncommon autoantibody demyelinating disorder of the central nervous system (CNS) with heterogeneous clinical manifestations and magnetic resonance imaging (MRI) findings. In recent years, a rare MOGAD subtype characterized by distinct clinical and MRI findings has been described. Seizures and cortical hyperintensities best seen on MRI T2-weighted fluid-attenuated inversion recovery (FLAIR) sequences, associated with headache and cerebral spine fluid (CSF) pleocytosis, are the most important characteristics of this MOGAD entity that is named FLAMES (FLAIR hyperintense cortical lesions in MOG-associated encephalitis with seizures). Because of its rarity and the peculiarities of the brain damage and clinical manifestations, it can be under-recognized and confused with focal viral encephalitis, meningitis, subarachnoid hemorrhage, CNS vasculitis, or mitochondrial cytopathy. We described the case of a 4-year-old previously healthy girl who was admitted for focal-onset, tonic-clonic seizures, fever, and headache, combined with optic neuritis. MRI was characterized by FLAIR imaging showing hyperintense cortical lesions, and a mild leukocytosis in the CSF was detected. Efficacy and rapid response to steroid therapy was observed, and no recurrences of neurological problems or further seizures were reported in the following 12 months. This case report can help in understanding FLAMES characteristics in pediatrics in order to favor early diagnosis and prompt therapy.

The "cortical invagination sign": a midtrimester sonographic marker of unilateral cortical focal dysgyria in fetuses with complete agenesis of the corpus callosum.

BACKGROUND: Agenesis of the corpus callosum is associated with several malformations of cortical development. Recently, features of focal cortical dysgyria have been described in fetuses with agenesis of the corpus callosum. OBJECTIVE: This study aimed to describe the "cortical invagination sign," a specific sonographic feature of focal cortical dysgyria, which is consistently seen at midtrimester axial brain ultrasound in fetuses with complete agenesis of the corpus callosum. STUDY DESIGN: This was a retrospective analysis of prospectively collected data from 2018 to 2021, including patients referred to 5 fetal medicine centers in the second trimester of pregnancy (19 0/7 to 22 0/7 weeks of gestation) with suspected complete agenesis of the corpus callosum. All cases with the diagnosis of complete agenesis of the corpus callosum were submitted to an axial sonographic assessment of the fetal brain on the transventricular plane. In this scanning section, the mesial profile of both cerebral hemispheres at the level of the frontal-parietal cortex was investigated. In this area, the operator looked for an abnormal invagination of the cortical surface along the widened interhemispheric fissure, which was referred to as the "cortical invagination sign." All fetuses were submitted to dedicated antenatal magnetic resonance imaging to reassess the ultrasound findings. Cases with additional brain anomalies, which did not involve the cortex, were excluded. The final diagnosis was confirmed at postnatal brain magnetic resonance imaging or postmortem examination, for cases undergoing termination of pregnancy. The primary outcome of this study was to evaluate the presence and laterality of the "cortical invagination sign" in fetuses with complete agenesis of the corpus callosum at antenatal ultrasound and magnetic resonance imaging. RESULTS: During the study period, 64 cases of complete agenesis of the corpus callosum were included; of those cases, 50 (78.1%) resulted in termination of pregnancy, and 14 (21.9%) resulted in a live birth. The "cortical invagination sign" was detected at ultrasound in 13 of 64 cases (20.3%) and at targeted brain magnetic resonance imaging in 2 additional cases (23.4%), all of which were electively terminated. Moreover, the "cortical invagination sign" was found to be exclusively unilateral and on the left cerebral hemisphere in all the cases. There was a predominant number, although nonsignificant, of male fetuses (80.0% of cases; P=.06) in the group of complete agenesis of the corpus callosum with the "cortical invagination sign." CONCLUSION: The "cortical invagination sign" is a specific marker of focal cortical dysgyria, which seems to characterize at midtrimester of pregnancy in a large group of fetuses with complete agenesis of the corpus callosum. The etiology, pathophysiology, and prognostic significance of this finding remain to be elucidated.

Case Report: short stature, kidney anomalies, and cerebral aneurysms in a novel homozygous mutation in the PCNT gene associated with microcephalic osteodysplastic primordial dwarfism type II.

We report the case of a boy (aged 3 years and 7 months) with severe growth failure (length: -9.53 SDS; weight: -9.36 SDS), microcephaly, intellectual disability, distinctive craniofacial features, multiple skeletal anomalies, micropenis, cryptorchidism, generalized hypotonia, and tendon retraction. Abdominal US showed bilateral increased echogenicity of the kidneys, with poor corticomedullary differentiation, and a slightly enlarged liver with diffuse irregular echotexture. Initial MRI of the brain, performed at presentation, showed areas of gliosis with encephalomalacia and diffused hypo/delayed myelination, and a thinned appearance of the middle and anterior cerebral arteries. Genetic analysis evidenced a novel homozygous pathogenic variant of the pericentrin (PCNT) gene. PCNT is a structural protein expressed in the centrosome that plays a role in anchoring of protein complexes, regulation of the mitotic cycle, and cell proliferation. Loss-of-function variants of this gene are responsible for microcephalic osteodysplastic primordial dwarfism type II (MOPDII), a rare inherited autosomal recessive disorder. The boy died at 8 years of age as a result of an intracranial hemorrhage due to a cerebral aneurism associated with the Moyamoya malformation. In confirmation of previously published results, intracranial anomalies and kidney findings were evidenced very early in life. For this reason, we suggest including MRI of the brain with angiography as soon as possible after diagnosis in follow-up of MODPII, in order to identify and prevent complications related to vascular anomalies and multiorgan failure.

A patient with mosaic USP9X gene variant.

The finding of USP9X variants in females has been associated with female-restricted X-linked mental retardation (MRXS99F), a rare syndrome featured by developmental delay and distinct congenital anomalies. Here, we report a female fetus with MRXS99F due to a novel frameshift variant, c.6679_6685delAAATTATinsTCCTG (p.Lys2227SerfsTer2) in USP9X, which was present in a mosaic state in the amniocytes and in the peripheral blood after birth (14% and 30%, respectively). The X methylation status analysis displayed a partially skewed X-inactivation with 80% of inactive paternal X. The first signs of the MRXS99F were prenatally detected at 20 weeks, with an enlarged posterior cranial fossa, an upward rotation of the cerebellar vermis and partial corpus callosum agenesis, together with a cardiac septal defect and a single umbilical artery. After birth and during postnatal follow-up the anal anteriorization and the presence of a bilateral membranous choanal atresia were noted, whereas the MRI revealed the hypo/aplasia of the olfactory bulbs, a widening of the subarachnoid spaces and a delay in the myelinisation. During the 18-months follow-up a severe growth and global developmental delay, together with a bilateral moderate deafness with a threshold at 40 dB, dental enamel erosions and an initial scoliosis were observed. We report the prenatal and postnatal features of a classical MRXS99F phenotype and a mosaic USP9X frameshift variant with a partially skewed X inactivation and discuss genotype/phenotype correlations in view of the published studies so far.

Role of prenatal magnetic resonance imaging in fetuses with isolated severe ventriculomegaly at neurosonography: A multicenter study.

OBJECTIVE: The aim of this study was to report the rate of additional anomalies detected exclusively at prenatal magnetic resonance imaging (MRI) in fetuses with isolated severe ventriculomegaly undergoing neurosonography. METHOD: Multicenter, retrospective, cohort study involving 20 referral fetal medicine centers in Italy, United Kingdom, Spain and Denmark. Inclusion criteria were fetuses affected by isolated severe ventriculomegaly (≥15 mm), defined as ventriculomegaly with normal karyotype and no other additional central nervous system (CNS) and extra-CNS anomalies on ultrasound. In all cases, a multiplanar assessment of fetal brain as suggested by ISUOG guidelines on fetal neurosonography had been performed. The primary outcome was the rate of additional CNS anomalies detected exclusively at fetal MRI within two weeks from neurosonography. Subgroup analyses according to gestational age at MRI (

Duplication of the Pituitary Gland (DPG)-Plus Syndrome Associated With Midline Anomalies and Precocious Puberty: A Case Report and Review of the Literature.

Duplication of the pituitary gland (DPG)-plus syndrome is a very rare developmental disorder with few cases described in the literature and characterized by multiple midline and central nervous system malformations. The hypothalamus and hypophysis involvement may be clinically associated with endocrine abnormalities. A 5.9-year-old female child was admitted to our Clinic for premature thelarche and acceleration of growth. DPG-plus syndrome with paired infundibula and pituitary glands was diagnosed after birth, when she appeared small for gestational age and she presented with lingual hypoplasia, cleft palate, right choanal stenosis, nasopharyngeal teratoma, and facial dysmorphisms. Neuroimaging revealed a duplication of the infundibula, the pituitary gland, and the dens of the epistropheus despite surgical removal of a rhino-pharyngeal mass performed at the age of two months. An array-CGH revealed a 2p12 deletion. At our evaluation, bone age assessment resulted advanced and initial pubertal activation was confirmed by Gonadotropin-Releasing Hormone stimulation test. Hormonal suppression treatment was started with satisfactory results. This case shows that DPG-plus syndrome must be considered in presence of midline and craniofacial malformations and endocrinological evaluations should be performed for the prompt and appropriate management of pubertal anomalies.

Multiple Acute Ischemic Strokes in a COVID-19 Patient: a Case Report.

We describe a case of a 47-year-old Italian, immunocompromised, and obese woman infected by COVID-19 presenting with fever (39.6 °C) and respiratory symptoms. Neurological examination was normal. Chest CT findings consist of bilateral interstitial pneumonia (visual score extension: 30%). The patient was treated with antiviral drugs and anti-inflammatory drugs with supportive care. Seven days after admission to Covid-19 Unit, the patient rapidly developed worsening respiratory failure and acute respiratory distress syndrome (ARDS). She suddenly developed partial left hemispheric syndrome. A new HRCT scan of her thorax revealed diffuse ground-glass opacities in both lungs (visual score extension: 90%). Brain CT performed 2 h after sudden-onset left-sided weakness showed subtle low attenuation within the right insular ribbon and frontal lobe (ASPECT Score 8). Multiphasic CT angiography (MCTA) demonstrated occlusion of both the dominant inferior division of the right middle cerebral artery and the A2 segment of the right anterior cerebral artery. After 24 h, her pupils became dilated and unreactive, and brain CT demonstrated large bilateral infarctions of both the cerebellar and cerebral hemispheres. She had a rapid progression of interstitial pneumonia from COVID-19, developed multiple strokes, and died 1 day later. SARS-CoV-2 infection seems to predispose pluripathological subjects to cerebrovascular complications.

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.

Transient posterior cerebral arteriopathy: An unusual case enterovirus-related.

Transient Cerebral Arteriopathy (TCA) is one of the main causes of childhood stroke. Here we present an unusual case of Arterial Ischemic Stroke (AIS) caused by a TCA of posterior flow and originally located in the right thalamus. The detection of enterovirus in the cerebrospinal fluid allowed us to suppose a probable post infectious etiology. The course of symptoms was self-limited and the child had a complete clinical recovery after five days. A new ischemic lesion on the antero-inferior paravermian region of the left cerebellum was revealed by a following brain Magnetic Resonance Imaging (MRI) three months later and these findings were reported by further brain MRI control performed after 15 months. Comparing follow up Magnetic Resonance Angiography (MRA) with previous High Resolution Vessel Wall Magnetic Resonance Imaging (HRMI), we found a vessel narrowing at the level of the Posterior Inferior Cerebellar Artery that might explain the arteriopathy process. In conclusion, clinical and radiological course allow us to speculate that this multifocal cerebral arteriopathy might be a transient lesion due to enterovirus infection. To our knowledge, there are only three articles describing TCA enterovirus-related, and brain MRA was performed in only one case; in addition, no one with the involvement of the posterior circulation.

A novel temporal pattern of childhood cerebral X-linked adrenoleukodystrophy.

We report a 9-year-old boy, with childhood cerebral X-linked adrenoleukodystrophy (CCALD), presenting with an episode of loss of consciousness, fixed gaze, hypotonia and vomit with spontaneous resolution and post-ictal sleep. Behavioural impairment has been observed since the previous five months. Magnetic Resonance Images (MRI) revealed isolated bilateral, symmetric, confluent temporal white matter lesions involving also corticospinal tracts, with sparing of the parieto-occipital and frontal white matter. This report outlines an atypical neuroradiological localization of X-linked adrenoleukodystrophy and neuropsychological findings not specifically related to the brain involvement seen at the MRI.

A painful stiff neck following an ear, nose, and throat surgical procedure: case report.

Grisel syndrome is a rare, nontraumatic atlantoaxial subluxation, typical of developmental ages and characterized by head flexion/rotation and painful fixation. Neurological symptoms may occur. It is secondary to head/neck infections and ear, nose, and throat surgery (adenoidectomy, tonsillectomy, and mastoidectomy). Here, we report the case of a child who presented a painful stiff neck following an adenotonsillectomy, with imaging evidencing an atlantoaxial subluxation. The child showed improvement in his condition following a conservative treatment with antibiotics, anti-inflammatory, and analgesic therapy and cervical collar. We believe it is of great significance for clinicians taking into account this peculiar condition in the differential diagnosis of a stiff neck in pediatric patients, thus avoiding misdiagnosis and delays. Indeed, its diagnosis is mainly based on a focused anamnesis associated with the detection of the typical neuroradiological findings.

Partitioned versus duplicated internal auditory canal: when appropriate terminology matters.

OBJECTIVE: A double internal auditory canal (IAC) is an uncommon malformation among temporal bone anomalies related to sensorineural hearing loss. This anomaly has been described as an isolated finding in otherwise normal patients, as well as a frequent feature in pontine tegmental cap dysplasia (PTCD). In both circumstances, the term duplication is currently used to describe this malformation. We conducted a retrospective study on 3 cases of IAC duplication (2 isolated and 1 PTCD-associated form) and reviewed the literature to evaluate both imaging features and differences between the 2 forms. INTERVENTION(S): All 3 patients underwent high-resolution computed tomography and magnetic resonance imaging. RESULTS: Neuroimaging documented different radiologic features between isolated and PTCD-associated IAC duplication. In the isolated form, the IAC seemed to have normal position and size, but it was partitioned in 2 portions by a complete or incomplete bony septum. Conversely, in the PTCD-associated form, neuroimaging revealed the presence of 2 separated and anomalously coursing canals for the facial and vestibulocochlear nerve. CONCLUSION: The aforementioned different radiologic findings probably reflect a more complex spectrum of etiopathogenetic mechanisms affecting the facioacoustic primordium and leading to overlapping anomalies of the IAC. We speculate on the appropriate terminology in describing this entity and propose that "partition" should be used to describe a double IAC otherwise normal in size and location; conversely, "duplication" should be reserved for IAC anomalies encountered in patients with PTCD or other hindbrain malformations.

Goldenhar syndrome associated with contralateral agenesis of the internal carotid artery.

Congenital absence of the internal carotid artery (ICA) is an extremely rare vascular anomaly. Aplasia and displacement of the horizontal portion of the petrous carotid artery have been described in a patient with mandibulofacial dysostosis. To the best of our knowledge, the association between Goldenhar syndrome and ipsilateral ICA agenesis has emerged only in one case documented in the medical literature to date. We describe here a case that illustrates the association of Goldenhar syndrome with contralateral agenesis of the ICA incidentally detected on brain magnetic resonance imaging and subsequently confirmed on magnetic resonance angiography and high resolution computed tomography.

Cochlear implantation in children with cochlear nerve deficiency.

OBJECTIVE: The aim of this study was to report on auditory performance after cochlear implantation in children with cochlear nerve deficiency. METHODS: A retrospective case review was performed. Five patients with pre-lingual profound sensorineural hearing loss implanted in an ear with cochlear nerve deficiency participated in the study. Postoperative auditory and speech performance was assessed using warble tone average threshold with cochlear implant, speech perception categories, and speech intelligibility ratings. All patients underwent high resolution computed tomography and magnetic resonance imaging. RESULTS: According to Govaerts classification, three children had a type IIb and two a type IIa cochlear nerve deficiency. Preoperatively, four patients were placed into speech perception category 1 and one into category 2. All patients had an improvement in hearing threshold with the cochlear implant. Despite this, at the last follow-up (range 18-81 months, average 45 months), only one girl benefited from cochlear implantation; she moved from speech perception category 2 to 6 and developed spoken language. Another child developed closed set speech perception and had connected speech that was unintelligible. The other 3 children showed little benefit from the cochlear implant and obtained only an improved access to environmental sounds and improved lipreading skills. None of these 4 children developed a spoken language, but they were all full-time users of their implants. CONCLUSIONS: The outcomes of cochlear implantation in these five children with cochlear nerve deficiency are extremely variable, ranging from sporadic cases in which open set speech perception and acquisition of a spoken language are achieved, to most cases in which only an improved access to environmental sound develops. Regardless of these limited outcomes, all patients in our series use their device on a daily basis and derive benefits in everyday life. In our opinion, cochlear implantation can be a viable option in children with cochlear nerve deficiency, but careful counseling to the family on possible restricted benefit is needed.

Unilateral ectopic parotid gland in CHARGE syndrome.

Unilateral absence of a parotid gland at the expected location is an extremely rare condition with only a few cases reported in the medical literature and, to our knowledge, never previously described in association with CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia of the choanae, Retardation of growth and/or development, Genital and/or urinary abnormalities, and Ear abnormalities and deafness). Although this entity is usually associated with a complex constellation of anomalies, additional findings have been described, including cranial nerve dysfunction (VII, VIII, IX and X). We present a case that illustrates the association of CHARGE syndrome with absence of parotid gland at normal location with ectopic parotid tissue lateral to masseter muscle, incidentally detected on brain MRI and subsequently confirmed on neck MRI.

Bilateral cerebellopontine angle lipomas.

Cerebellopontine angle (CPA) lipomas are extremely rare lesions and usually unilateral. We describe a case of a 36-year-old man with bilateral aural fullness that was discovered to have bilateral CPA lipomas associated with an abnormal hindbrain segmentation appearance. The patient was evaluated with 3.0T magnetic resonance imaging (MRI) system. MRI demonstrated the presence of bilateral CPA masses partially extending into the internal auditory canals. These lesions were hyperintense on both T1- and T2 weighted images. Facial and vestibulo-cochlear nerves together with tortuous vascular structures and fibro-connective septa were identified on T2-weighted 3D Fast Imaging Employing Steady-state Acquisition (FIESTA) sequences as areas of lower intensity coursing through the masses. Gadolinium administration yielded no enhancement. Conservative management was adopted.

Pontine Tegmental Cap Dysplasia: developmental and cognitive outcome in three adolescent patients.

Pontine Tegmental Cap Dysplasia (PTCD) is a recently described, rare disorder characterized by a peculiar cerebellar and brainstem malformation. Nineteen patients have been reported to date, of which only one in the adolescent age, and data on the clinical, cognitive and behavioural outcome of this syndrome are scarce. Here we describe three adolescent patients with PTCD. All presented bilateral deafness and multiple cranial neuropathies, variably associated with skeletal, cardiac and gastro-intestinal malformations. Feeding and swallowing difficulties, that are often causative of recurrent aspiration pneumonias and death in the first years of life, completely resolved with age in all three patients. Neuropsychological assessment showed borderline to moderate cognitive impairment, with delay in adaptive functioning, visual-spatial and language deficits. Two of three patients also showed mild behavioural problems, although their overall socialization abilities were well preserved. Cochlear implantation in two patients significantly improved their relational and learning abilities. Fibre tractography confirmed the abnormal bundle of transversely oriented fibres forming the typical pontine "tegmental cap" and absence of decussation of the superior cerebellar peduncles, supporting the hypothesis that PTCD results from abnormal axonal guidance and/or migration.These data indicate that PTCD may have a favourable long-term outcome, with borderline cognitive deficit or even normal cognition and partially preserved speech.

Cochlear implantation in pontine tegmental cap dysplasia.

Pontine tegmental cap dysplasia (PTCD) is an exceptionally rare brain stem and cerebellar malformation characterized by ventral pontine hypoplasia, vaulted pontine tegmentum, hypoplasia of the vermis, subtotal absence of middle cerebellar peduncles, lateralized course of the superior cerebellar peduncles, and absence or alteration of the inferior olivary nucleus. The main clinical features are multiple cranial neurophaties and ataxia. Sensorineural hearing loss of varying severity is almost always present. To date, 14 cases of PTCD have been reported in the literature. We present a child with PTCD and profound bilateral sensorineural hearing loss who underwent cochlear implantation. To the best of our knowledge, cochlear implantation in PTCD has not been previously reported. Functional outcome was assessed using the Speech Perception Categories and the Speech Intelligibility Rating scale. At 22 months' postoperative evaluation, the patient who was placed into speech perception category 0 (no detection of speech) preoperatively progressed to category 3 (beginning word identification). Before implantation, the child had connected speech unintelligible. At the last follow-up, she had connected speech intelligible to a listener who has little experience of a deaf person's speech. Cochlear implantation allowed this child to improve her quality of life, increasing her self-confidence, independence, and social integration.