Early Diagnosis of Tuberous Sclerosis Complex: Prenatal Diagnosis.

BACKGROUND AND PURPOSE: Strong emphasis has been placed recently on early (4 postnatal months) detection of tuberous sclerosis complex and the introduction of antiepileptic treatment before seizure onset. This objective can be achieved prenatally: Cardiac rhabdomyomas and the major diagnostic tuberous sclerosis complex sign are detected during fetal ultrasound, and prenatal MR imaging allows detection of cerebral major manifestations: cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas. MATERIALS AND METHODS: We retrospectively reviewed 50 fetuses with ultrasound-detected cardiac tumors at 19-36 gestational weeks (median, 31 weeks). MR imaging with the use of 1.5T scanners was performed at 24-37 gestational weeks (median, 34 weeks). RESULTS: In 11 fetuses (22%), cardiac tumors remained the only criterion. In remaining 39 fetuses (78%), MR imaging revealed a prenatal diagnosis of tuberous sclerosis complex, having shown an additional 1-3 major criteria: subependymal nodules in all cases (39/39 = 100.0%), subependymal giant cell astrocytomas in 6 (6/39 = 15.4%), and cortical tubers in 24 (24/39 = 61.5%). Radial migration lines and cerebellar tuber, not published so far, were shown in 1 case each. CONCLUSIONS: A schedule of proper care of children with tuberous sclerosis complex can be established during the perinatal period due to education of women to report for mandatory ultrasound examinations during pregnancy, the good quality of ultrasound, and referral to MR imaging if a cardiac tumor is depicted on ultrasound. Gynecologists and pediatric cardiologists performing fetal ultrasound and radiologists performing prenatal MR imaging are a key to early diagnosis of tuberous sclerosis complex in many cases.

Thermal Index for early non-invasive assessment of brain injury in newborns treated with therapeutic hypothermia: preliminary report.

Perinatal asphyxia (PA) is the 3rd most common cause of neonatal death and one of the most common causes of severe neurological impairments in children. Current tools and measurements mainly based on the analysis of clinical evaluation and laboratory and electrophysiological tests do not give consistent data allowing to predict the severity of hypoxic-ischemic encephalopathy (HIE) until a magnetic resonance imaging (MRI) score is performed. The aim of this work is to evaluate the usefulness of the new index, called Thermal Index (TI) in the assessment of the degree of brain damage in newborns in the course of therapeutic hypothermia (TH) due to PA. This was a prospective, observational, pilot study which did not require any changes in the applicable procedures. Analysis has been applied to six newborn babies treated with TH in Neonatal/Paediatric ICU in University Hospital in Opole in 2018 due to PA. They all met criteria for TH according to the current recommendations. Brain MRI was performed after the end of TH when the children were brought back to normal temperature, with the use of a 1.5 T scanner, using T1-, T2-weighted images, fluid-attenuated inversion recovery (FLAIR), inversion recovery (IR), susceptibility-weighted imaging (SWI), and diffusion-weighted imaging (DWI). The images were assessed using MRI score according to the scoring system proposed by Weeke et al. The Thermal Index assessing endogenous heat production was calculated according to the formula proposed in this paper. A high, statistically significant positive correlation was found between MRI scores and TI values (0.98; p = 0.0003) in the 1st hour of therapy. High correlation with MRI assessment, the non-invasiveness of measurements and the availability of results within the first few hours of treatment, allow authors to propose the Thermal Index as a tool for early evaluating of the brain injury in newborns treated with TH. Further research is required to confirm the usefulness of the proposed method.

Hypomyelinating leukodystrophies - a molecular insight into the white matter pathology.

Hypomyelinating leukodystrophies (HLDs) are a group of neurodevelopmental disorders that affect proper formation of the myelin sheath in the central nervous system. They are characterized by developmental delay, hypotonia, spasticity, and variable intellectual disability. In the past various classification systems for HLDs have been used, based on imaging findings, clinical manifestation, and organelle-specific disorders. Here we present a molecular insight into HLDs based on a defect in specific gene engaged in myelination. We discuss recent findings on pathogenesis, clinical presentation, and imaging related to these disorders. We focus on HLDs that are in use in differential diagnostics of Pelizaeus-Merzbacher disease (PMD), with a special emphasis on Allan-Herndon-Dudley syndrome (AHDS), an X-linked condition with delayed myelination due to thyroid transport disturbances. On the background of previously published patients we describe a proband initially considered as presenting with a severe PMD, whose diagnosis of AHDS due to a novel nonsense SLC16A2 mutation unraveled two previously undiagnosed generations of affected males who died in infancy from unexplained reasons. Since AHDS is found to be a relatively frequent cause of X-linked intellectual disability, we emphasize the need for determining the whole thyroid profile especially in hypotonic males with a delay of psychomotor development.

Diffusion-Weighted Imaging of the Early Phase of Wallerian Degeneration. A Report of two Pediatric Cases and Literature Review.

Wallerian degeneration (WD) affects axons and their myelin sheaths distally from the site of injury of the axon and/or body of the neuron. There is limited knowledge about brain injuries in newborns, mostly because non-invasive imaging sensitive enough to detect subtle changes was not available. Diffusion-weighted magnetic resonance (MR) imaging (DWI) is sensitive in the detection of early injury to the corticospinal tracts (CST) before the occurrence of WD in distal segments. We describe the cases of 14- and seven-day-old newborns in whom MR imaging revealed vascular injury in the territory supplied by the middle cerebral artery, and early development of WD. We performed DWI and faced an unexpected finding because DWI hyperintensities were at the same time hyperintense on T2-weighted images. Hyperintense structures on DWI are supposed to reflect pre-Wallerian injured tissue, which should not be visible on standard MR sequences, while their T2- signal indicated the third, late subacute phase of WD. It seems that time-related stages of WD observed in adults do not necessarily apply to the immature brain of newborns/infants as reflected by differences in signal intensity in various MR sequences. DWI hyperintensity in CST below infarct should not be mistaken for new ischemic foci.

Proton MR Spectroscopy in Patients with Leigh Syndrome.

The aim of the present study was to evaluate MRS findings in patients with Leigh syndrome. We report our results of HMR spectroscopic studies performed in six patients (aged four months to ten years) with clinically proved Leigh syndrome. All examinations were done with 1.5 T scanner using an eight-channel phased array head coil. HMRS data were obtained using 2D-chemical shift imaging (CSI) and SVS sequences with short (30 ms) and long (135 ms) echo time. The MR spectra were acquired in multiple voxel localized in deep gray matter and periventricular white matter. The results were compared to the control group data. In most of our patients we found bilateral lesions in the basal ganglia and brain stem. HMRS data revealed elevated lactate in the affected areas, significantly diminished NAA/Cr ratio. The relatively high Cho/Cr ratio in the gray and white matter was also noted. HMRS is an important tool for non-invasive brain tissue analysis in Leigh syndrome.

Congenital CNS tumors diagnosed on prenatal MRI.

Congenital tumors form a unique group among pediatric neoplasms. They are different from other tumor groups in this population not only due to the onset time but also to their histopathology, anatomic location, biologic behavior and prognosis. The development of fetal MRI allowed early diagnosis of these tumors. Three fetuses with congenital central nervous system (CNS) tumors were diagnosed prenatally and confirmed with histopathology. Prenatal ultrasonography (US) and magnetic resonance imaging (MRI) were performed. After birth MRI or computed tomography (CT) were carried out. In one case a large intra-axial brain tumor was diagnosed with solid, cystic and hemorrhagic elements. After surgery the tumor turned out to be choroid plexus carcinoma. In the second case craniopharyngioma arising from the suprasellar region was diagnosed on the basis of prenatal MRI and confirmed. In the third case extra-axial meningioma-like tumor was visualized on fetal MRI. After surgery it turned out to be desmoplastic infantile astrocytoma. Intracranial teratoma, the most typical CNS congenital tumor, was not diagnosed in our material. Our cases were rarely encountered neoplasms: choroid plexus carcinoma, craniopharyngioma and desmoplastic infantile astrocytoma. The examinations were repeated after birth and did not add significant information. In utero diagnostics is easier and safer than postnatal imaging of the sick baby that may require life-support equipment, and provides information of equal value.

Brain Metastases from Ewing's Sarcoma. A Report of Two Cases and Review of the Literature.

Ewing's sarcoma accounts for approximately 30% of primary malignant bone tumors, mainly in children and young adults. At the time of diagnosis many patients already have metastatic spread of the disease, most often to the lungs and skeletal system. Intracerebral metastases are rare - the reported incidence is up to 4.3%. We describe two cases of metastatic deposits within the brain tissue. Signal intensity of the lesions was similar to that of meningioma on all sequences. Strong homogenous enhancement after gadolinium administration was also similar to meningioma.

Brain MRI in fetuses with cardiac tumours.

Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder which affects the skin, brain, heart and other organs. It is caused by mutations of two genes: TSC1 (on chromosome 9q34) or TSC2 (on 16p13.3). 70% of cases are sporadic with new mutations. This study aimed to highlight the utility of prenatal MRI as an adjunct imaging modality in the diagnosis and prognosis of tuberous sclerosis complex. Prenatal ultrasound and magnetic resonance imaging were performed in seven fetuses at a gestational age of 30, 32, 34 and 35 weeks using a 1.5 T MRI scanner. SSFSE,T2- and FGRE/T1-weighted images were obtained in axial, coronal and sagittal planes. Postnatal MRI was performed in two cases. Intracardiac tumors (rhabdomyomas) were revealed on ultrasound in all fetuses. On sonographic examination the brain tissue appeared normal in all cases. Brain MRI revealed focal low-signal-intensity lesions, localized along the walls of the lateral ventricles of five fetuses. Another hypointense lesion was seen at the grey/white matter junction in one case. Brain MRI of two fetuses was normal. The diagnosis of TSC was established in five cases. Postnatal MRI in two cases confirmed prenatal findings. MRI allows more complete evaluation of the fetus and helps to determine the diagnosis and prognosis in cases of TSC. The use of prenatal MR imaging in addition to prenatal sonography has the potential to improve genetic counseling and prenatal diagnosis of patients with tuberous sclerosis.

Apparent diffusion coefficient is increased in children with tuberous sclerosis complex personal experience and review of the literature.

Diffusion-weighted imaging (DWI) provides information on tissue integrity and shows increased sensivity in detecting brain white matter disease compared to traditional T2-weighted MRI. We compared apparent diffusion coefficient (ADC) values in brain lesions and normal appearing white matter (NAWM) in patients with tuberous sclerosis complex (TSC) to normal brain tissue in the control group. MRI and DWI were performed in 14 patients with TSC (age range 7-16 years) and in 18 age-matched normal control subjects. ADC values measured from 44 supratentorial cortical tubers, 37 white matter lesions, 80 NAWM were compared to those in control subjects. Statistical analysis was performed using Kruskal-Wallis and Mann-Whitney U tests. The highest ADCs were measured in cortical tubers (mean ADC, 1.24×10-3 mm(2)/s), followed in descending order by WM lesions (mean ADC, 1.07×10-3 mm(2)/s), NAWM (mean ADC, 0.83×10-3 mm(2)/s). We found a significant difference in ADC values of gray, WM lesions and NAWM in TSC patients compared to the control group (p<0,0001). Elevated ADC values in NAWM in TSC patients may be caused by subtle depletion of myelin sheaths and looseness of structures within the brain parenchyma due to underlying migration disorders.

Letter to the editor. A case of inborn choroid plexus carcinoma.

This is a short comment on the article by Balaji et al. "CT and MR Imaging in Choroid Plexus Carcinoma. Report of Two Cases" (The Neuroradiology Journal 2006, 19: 330-333).

Cerebellar lesions in children with tuberous sclerosis complex.

Cerebellar lesions in tuberous sclerosis complex are less frequent than cerebral findings. We present the magnetic resonance (MR) features of uncommon cerebellar changes found in a large series of children with tuberous sclerosis complex (TSC). MR examinations of 73 children (38 males and 35 females) with TSC were reviewed. Twelve patients with cerebellar lesions were selected. Patients' ages ranged from 2.5 years to 21.25 (median: 10.6). The number, anatomic location, signal intensity and contrast enhancement of these lesions were evaluated. MR studies were performed with a 1.5 T scanner obtaining T1, T2-weighted images and FLAIR sequences. Gadolinium was administrated in all cases. Cerebellar tubers were found in 12 patients (16.4%). The total number of cerebellar tubers was 21. Most cerebellar tubers were hyperintense on T2-weighted and FLAIR images and slightly hypointense on T1-weighted images. Eleven of these lesions (52.38%) revealed contrast enhancement. None of cortical cerebral tubers showed contrast enhancement. Atrophy of seven cerebellar tubers was noticed. The mutation in TSC2 gene was confirmed in eight patients. Cerebellar tubers are uncommon. They were not found in the absence of cerebral tubers and may associated with parenchymal volume loss.

MRI of the hypophysis in a patient with the 18q- syndrome.

We present a 3.5-year-old girl with proven 18q- syndrome. MRI revealed hypoplasia of the anterior pituitary, marked thinning of the corpus callosum and enlargement of the ventricles.

MR imaging of seven presumed cases of central pontine and extrapontine myelinolysis.

MRI was performed in seven patients with presumed central pontine and extrapontine myelinolysis. The underlying diseases were diabetes, lung cancer, Wilson disease, trauma, alcoholism, renal insufficiency and hemodialysis. CPM was found in four cases (in two of them extrapontine lesions were considered as resulting from Wilson disease), CPM and EPM in three patients. The localization of extrapontine changes included cerebellum, cerebral peduncles, caudate and lentiform nuclei, internal capsules, white matter and cortex of the cerebrum.

Menkes' disease with a Dandy-Walker variant: case report.

We report a boy with Menkes' disease in whom MRI revealed delayed myelination of the white matter, brain atrophy and tortuosity of the intracranial vessels. The characteristic MRI features of Menkes' disease were accompanied by a Dandy-Walker variant.

MRI findings in an asymptomatic boy with X-linked adrenoleukodystrophy and his symptomatic mother.

We report an asymptomatic 15-year-old boy with X-linked adrenoleukodystrophy and his symptomatic 38-year-old mother. MRI revealed similar, subtle high-signal lesions in the periventricular white matter of the parieto-occipital regions, without involvement of the corpus callosum, more pronounced in the mother.

[MRI in the diagnosis of congenital white matter diseases and other neurodegenerative diseases]. / Wartosc rezonansu magnetycznego w diagnostyce wrodzonych chorób istoty bialej i innych zwyrodnieniowych chorób osrodkowego ukladu nerwowego.

The results of cranial magnetic resonance imaging in 76 children (aged 3 weeks--17 years) with neurometabolic or other neurodegenerative diseases are presented. The number of diagnosed diseases was 22. MR symptomatology of 11 of them is presented. The list of characteristic images includes metachromatic leukodystrophy, mucopolysaccharidoses, X-linked adrenoleukodystrophy, Leigh, Menkes and Pelizaeus-Merzbacher diseases, glutaric aciduria type I, Canavan disease, neuronal ceroid lipofuscinosis, Hallervorden-Spatz and Huntington diseases. The diagnosis of neurometabolic/neurodegenerative diseases cannot be based on MRI alone but in some of them (metachromatic leukodystrophy, adrenoleukodystrophy, Leigh and Menkes diseases, glutaric aciduria type I, Canavan and Hallervorden-Spatz diseases) MRI can strongly suggest the diagnosis.

[Corpus callosum pathological lesions in computed tomography and magnetic resonance imaging]. / Patologia ciala modzelowatego w obrazach tomografii komputerowej i rezonansu magnetycznego.

The spectrum of congenital anomalies and other pathologic changes of the corpus callosum is presented. Callosal agenesis and hypoplasia, lesions in cases of congenital neurometabolic disorders, traumatic, vascular, inflammatory and neoplastic conditions as well as callosal atrophy are discussed. CT and MR images from the authors' own experience illustrate the material.