ABSTRACT
BACKGROUND AND PURPOSE: Ganglionic eminence abnormalities on fetal MR imaging are associated with cerebral malformations. Their presumed genetic basis and associated postnatal outcomes remain largely unknown. We aimed to elucidate these through a multicenter study. MATERIALS AND METHODS: Between January 2010 and June 2020, seven hospitals in 2 countries performing fetal MR imaging examinations identified fetal MR imaging studies demonstrating ganglionic eminence enlargement, cavitation, or both. Cases with no genetic diagnosis, no whole exome sequencing, or no outcome of a liveborn child were excluded. Head size was classified as large (fronto-occipital diameter > 95th centile), small (fronto-occipital diameter <5th centile), or normal. RESULTS: Twenty-two fetuses with ganglionic eminence abnormalities were identified. Of 8 with large heads, 2 were diagnosed with MTOR mutations; 1 with PIK3CA mutation-producing megalencephaly, polymicrogyria, polydactyly, hydrocephalus (MPPH) syndrome; 3 with TSC mutations; 1 with megalencephaly capillary malformation syndrome; and 1 with hemimegalencephaly. Cardiac rhabdomyoma was present prenatally in all cases of TSC; mutation postaxial polydactyly accompanied megalencephaly capillary malformation and MPPH. Of 12 fetuses with small heads, 7 had TUBA1A mutations, 1 had a TUBB3 mutation, 2 had cobblestone lissencephaly postnatally with no genetic diagnosis, 1 had a PDHA1 mutation, and 1 had a fetal akinesia dyskinesia sequence with no pathogenic mutation on trio whole exome sequencing. One of the fetuses with a normal head size had an OPHN1 mutation with postnatal febrile seizures, and the other had peri-Sylvian polymicrogyria, seizures, and severe developmental delay but no explanatory mutation on whole exome sequencing. CONCLUSIONS: Fetal head size and extracranial prenatal sonographic findings can refine the phenotype and facilitate genetic diagnosis when ganglionic eminence abnormality is diagnosed with MR imaging.
Subject(s)
Hydrocephalus , Megalencephaly , Polydactyly , Polymicrogyria , Female , Fetus , Humans , Polydactyly/diagnostic imaging , Polydactyly/genetics , PregnancyABSTRACT
BACKGROUND AND PURPOSE: The ganglionic eminences are transient fetal brain structures that produce a range of neuron types. Ganglionic eminence anomalies have been recognized on fetal MR imaging and anecdotally found in association with a number of neurodevelopmental anomalies. The aim of this exploratory study was to describe and analyze the associations between ganglionic eminence anomalies and coexisting neurodevelopmental anomalies. MATERIALS AND METHODS: This retrospective study includes cases of ganglionic eminence anomalies diagnosed on fetal MR imaging during a 20-year period from 7 centers in Italy and England. Inclusion criteria were cavitation or increased volume of ganglionic eminences on fetal MR imaging. The studies were analyzed for associated cerebral developmental anomalies: abnormal head size and ventriculomegaly, reduced opercularization or gyration, and abnormal transient layering of the developing brain mantle. The results were analyzed using χ2 and Fisher exact tests. RESULTS: Sixty fetuses met the inclusion criteria (21 females, 24 males, 15 sex unknown). Thirty-four had ganglionic eminence cavitations (29 bilateral and 5 unilateral), and 26 had increased volume of the ganglionic eminences (19 bilateral, 7 unilateral). Bilateral ganglionic eminence cavitations were associated with microcephaly (P = .01), reduced opercularization, (P < .001), reduced gyration (P < .001), and cerebellar anomalies (P = .01). Unilateral ganglionic eminence cavitations were not significantly associated with any particular feature. Bilateral increased volume of the ganglionic eminences showed an association with macrocephaly (P = .03). Unilateral increased volume was associated with macrocephaly (P = .002), abnormal transient layering (P = .001), unilateral polymicrogyria (P = .001), and hemimegalencephaly (P < .001). CONCLUSIONS: Ganglionic eminence anomalies are associated with specific neurodevelopmental anomalies with ganglionic eminence cavitations and increased ganglionic eminence volume apparently having different associated abnormalities.
Subject(s)
Magnetic Resonance Imaging , Brain , Female , Fetus/diagnostic imaging , Humans , Male , Pregnancy , Prenatal Diagnosis , Retrospective StudiesABSTRACT
INTRODUCTION: Cri-du-Chat Syndrome (CdCS) is a genetic condition due to deletions showing different breakpoints encompassing a critical region on the short arm of chromosome 5, located between p15.2 and p15.3, first defined by Niebuhr in 1978. The classic phenotype includes a characteristic cry, peculiar facies, microcephaly, growth retardation, hypotonia, speech and psychomotor delay and intellectual disability. A wide spectrum of clinical manifestations can be attributed to differences in size and localization of the 5p deletion. Several critical regions related to some of the main features (such as cry, peculiar facies, developmental delay) have been identified. The aim of this study is to further define the genotype-phenotype correlations in CdCS with particular regards to the specific neuroradiological findings. PATIENTS AND METHODS: Fourteen patients with 5p deletions have been included in the present study. Neuroimaging studies were conducted using brain Magnetic Resonance Imaging (MRI). Genetic testing was performed by means of comparative genomic hybridization (CGH) array at 130 kb resolution. RESULTS: MRI analyses showed that isolated pontine hypoplasia is the most common finding, followed by vermian hypoplasia, ventricular anomalies, abnormal basal angle, widening of cavum sellae, increased signal of white matter, corpus callosum anomalies, and anomalies of cortical development. Chromosomal microarray analysis identified deletions ranging in size from 11,6 to 33,8 Mb on the short arm of chromosome 5. Then, we took into consideration the overlapping and non-overlapping deleted regions. The goal was to establish a correlation between the deleted segments and the neuroradiological features of our patients. CONCLUSIONS: Performing MRI on all the patients in our cohort, allowed us to expand the neuroradiological phenotype in CdCS. Moreover, possible critical regions associated to characteristic MRI findings have been identified.
Subject(s)
Brain/diagnostic imaging , Brain/pathology , Cri-du-Chat Syndrome/diagnostic imaging , Cri-du-Chat Syndrome/pathology , Adolescent , Adult , Child , Child, Preschool , Cri-du-Chat Syndrome/genetics , Female , Genetic Association Studies , Humans , Infant , Infant, Newborn , Magnetic Resonance Imaging/methods , Male , Young AdultABSTRACT
BACKGROUND AND PURPOSE: Evaluation of biometry is a fundamental step in prenatal brain MR imaging. While different studies have reported reference centiles for MR imaging biometric data of fetuses in the late second and third trimesters of gestation, no one has reported them in fetuses in the early second trimester. We report centiles of normal MR imaging linear biometric data of a large cohort of fetal brains within 24 weeks of gestation. MATERIALS AND METHODS: From the data bases of 2 referral centers of fetal medicine, accounting for 3850 examinations, we retrospectively collected 169 prenatal brain MR imaging examinations of singleton pregnancies, between 20 and 24 weeks of gestational age, with normal brain anatomy at MR imaging and normal postnatal neurologic development. To trace the reference centiles, we used the CG-LMS method. RESULTS: Reference biometric centiles for the developing structures of the cerebrum, cerebellum, brain stem, and theca were obtained. The overall interassessor agreement was adequate for all measurements. CONCLUSIONS: Reference biometric centiles of the brain structures in fetuses between 20 and 24 weeks of gestational age may be a reliable tool in assessing fetal brain development.
Subject(s)
Brain/embryology , Fetal Development , Pregnancy Trimester, Second , Biometry/methods , Cohort Studies , Female , Humans , Male , Neuroimaging , Pregnancy , Reference Values , Retrospective StudiesABSTRACT
Diencephalic-mesencephalic junction dysplasia is a rare malformation characterized by a poorly defined junction between the diencephalon and the mesencephalon, associated with a characteristic butterfly-like contour of the midbrain (butterfly sign). This condition may be variably associated with other brain malformations, including callosal abnormalities and supratentorial ventricular dilation, and is a potential cause of developmental hydrocephalus. Here, we have reported 13 fetuses with second-trimester obstructive ventriculomegaly and MR features of diencephalic-mesencephalic junction dysplasia, correlating the fetal imaging with available pathology and/or postnatal data. The butterfly sign can be clearly detected on axial images on fetal MR imaging, thus allowing for the prenatal diagnosis of diencephalic-mesencephalic junction dysplasia, with possible implications for the surgical management of hydrocephalus and parental counseling.
Subject(s)
Diencephalon/abnormalities , Diencephalon/diagnostic imaging , Mesencephalon/abnormalities , Mesencephalon/diagnostic imaging , Nervous System Malformations/diagnostic imaging , Adult , Female , Fetus , Gestational Age , Humans , Hydrocephalus/congenital , Hydrocephalus/diagnostic imaging , Magnetic Resonance Imaging , Pregnancy , Pregnancy Trimester, Second , Prenatal DiagnosisABSTRACT
OBJECTIVES: To describe changes in umbilical artery (UA) Doppler flow in monochorionic diamniotic (MCDA) twins affected by selective intrauterine growth restriction (sIUGR), to correlate Doppler findings with pregnancy course and perinatal outcome, and to report postnatal follow-up. METHODS: This was a retrospective study of 140 MCDA twins with sIUGR. UA end-diastolic flow, defined as Doppler waveform pattern Type I (persistently positive), Type II (persistently absent or persistently reversed) or Type III (intermittently absent or intermittently reversed), was recorded at first examination and monitored weekly until double or single intrauterine fetal death (IUFD), bipolar cord coagulation or delivery. All neonates had an early neonatal brain scan, magnetic resonance imaging, when indicated, and neurological assessment during infancy. Rates (per 100 person-weeks) and hazard ratios (HR) of IUFD in the IUGR twin in each pregnancy were calculated considering UA Doppler pattern as a time-dependent variable. RESULTS: At first examination, there were 65 cases with UA Doppler waveform pattern Type I, 62 with Type II and 13 with Type III. Of the 65 Type-I cases, 48 (74%) remained stable, while 17 (26%) changed to either Type II absent (14%), Type II reversed (9%) or Type III (3%). Of 62 Type-II cases (47 with absent and 15 with reversed flow), 33 (53%) remained stable (18 with absent and all 15 with reversed flow). The 29 Type-II absent cases which changed became Type II reversed (24/47, 51%) or Type III (5/47, 11%). All 13 Type-III cases remained stable. Compared with Type I, the risk of IUFD (adjusted for estimated fetal weight discordance and amniotic fluid deepest vertical pocket) was highest when the pregnancy was or became Type II reversed (HR, 9.5; 95% CI, 2.7-32.7) or Type II absent (HR, 4.3; 95% CI, 1.3-14.3). Mild neurological impairment was more prevalent in the IUGR twin than in the large cotwin (7% vs 1%, P = 0.02). CONCLUSIONS: Risk stratification based on UA Doppler is useful for planning ultrasound surveillance. However, patterns can change over time, with important consequences for management and outcome. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Subject(s)
Diseases in Twins/diagnostic imaging , Fetal Growth Retardation/diagnostic imaging , Ultrasonography, Doppler/methods , Ultrasonography, Prenatal/methods , Umbilical Arteries/diagnostic imaging , Adult , Female , Humans , Maternal Age , Predictive Value of Tests , Pregnancy , Pregnancy Outcome , Retrospective Studies , Twins, Monozygotic , Young AdultABSTRACT
BACKGROUND AND PURPOSE: In several countries, laws and regulations allow abortion for medical reasons within 24-25 weeks of gestational age. We investigated the diagnostic value of prenatal MR imaging for brain malformations within 25 weeks of gestational age. MATERIALS AND METHODS: We retrospectively included fetuses within 25 weeks of gestational age who had undergone both prenatal and postnatal MR imaging of the brain between 2002 and 2014. Two senior pediatric neuroradiologists evaluated prenatal MR imaging examinations blinded to postnatal MR imaging findings. With postnatal MR imaging used as the reference standard, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the prenatal MR imaging in detecting brain malformations. RESULTS: One-hundred nine fetuses (median gestational age at prenatal MR imaging: 22 weeks; range, 21-25 weeks) were included in this study. According to the reference standard, 111 malformations were detected. Prenatal MR imaging failed to detect correctly 11 of the 111 malformations: 3 midline malformations, 5 disorders of cortical development, 2 posterior fossa anomalies, and 1 vascular malformation. Prenatal MR imaging misdiagnosed 3 findings as pathologic in the posterior fossa. CONCLUSIONS: The diagnostic value of prenatal MR imaging between 21 and 25 weeks' gestational age is very high, with limitations of sensitivity regarding the detection of disorders of cortical development.
Subject(s)
Brain/abnormalities , Brain/diagnostic imaging , Fetus/abnormalities , Fetus/diagnostic imaging , Prenatal Diagnosis/methods , Female , Gestational Age , Humans , Magnetic Resonance Imaging/methods , Pregnancy , Retrospective Studies , Sensitivity and SpecificityABSTRACT
BACKGROUND AND PURPOSE: Agenesis of the corpus callosum, even when isolated, may be characterized by anatomic variability. The aim of this study was to describe the types of other forebrain commissures in a large cohort of randomly enrolled fetuses with apparently isolated agenesis of the corpus callosum at prenatal MR imaging. MATERIALS AND METHODS: All fetuses with apparent isolated agenesis of the corpus callosum undergoing prenatal MR imaging from 2004 to 2014, were evaluated for the presence of the anterior or a vestigial hippocampal commissure assessed in consensus by 2 pediatric neuroradiologists. RESULTS: Overall, 62 cases of agenesis of the corpus callosum were retrieved from our data base. In 3/62 fetuses (4.8%), no forebrain commissure was visible at prenatal MR imaging, 23/62 fetuses (37.1%) presented with only the anterior commissure, and 20/62 fetuses (32.3%) showed both the anterior commissure and a residual vestigial hippocampal commissure, whereas in the remaining 16/62 fetuses (25.8%), a hybrid structure merging a residual vestigial hippocampal commissure and a rudiment of the corpus callosum body was detectable. Postnatal MR imaging, when available, confirmed prenatal forebrain commissure findings. CONCLUSIONS: Most fetuses with apparent isolated agenesis of the corpus callosum showed at least 1 forebrain commissure at prenatal MR imaging, and approximately half of fetuses also had a second commissure: a vestigial hippocampal commissure or a hybrid made of a hippocampal commissure and a rudimentary corpus callosum body. Whether such variability is the result of different genotypes and whether it may have any impact on the long-term neurodevelopmental outcome remains to be assessed.
Subject(s)
Agenesis of Corpus Callosum/pathology , Fornix, Brain/abnormalities , Diagnostic Imaging , Fetus , HumansABSTRACT
OBJECTIVE: The aim of this research was to determine the prevalence and sonographic appearance of the hippocampal commissure in fetuses with isolated complete agenesis of the corpus callosum by three-dimensional neurosonography in the multiplanar mode. METHODS: This was a multicenter observational study. Stored volume datasets of fetuses with isolated complete agenesis of the corpus were retrospectively retrieved for analysis in three tertiary centers. The presence or absence of the hippocampal commissure was independently evaluated in the coronal and midsagittal planes by two operators. Postnatal follow-up was obtained in all cases. RESULTS: From November 2007 to February 2013, 41 cases between 19 and 30 weeks of gestation were retrieved for analysis. The hippocampal commissure was visible in the coronal and sagittal planes in 27/41 (65.8%), absent or not clearly recognizable in the remaining 14 cases. The qualitative analysis of the two operators was concordant in 100% of cases. CONCLUSIONS: In more than half of fetuses with complete callosal agenesis, the hippocampal commissure may be visualized at prenatal ultrasound. This is a residual interhemispheric connection, which in normal cases is hidden by the corpus callosum itself. Further research is needed to establish if this has an impact on postnatal outcome.
Subject(s)
Agenesis of Corpus Callosum/diagnostic imaging , Fornix, Brain/diagnostic imaging , Ultrasonography, Prenatal , Adult , Agenesis of Corpus Callosum/embryology , Female , Follow-Up Studies , Fornix, Brain/abnormalities , Fornix, Brain/embryology , Humans , Imaging, Three-Dimensional , Pregnancy , Retrospective Studies , Ultrasonography, Prenatal/methodsABSTRACT
SUMMARY: Ganglionic eminence is the main transitory proliferative structure of the ventral telencephalon in human fetal brain and it contributes for at least 35% to the population of cortical interneurons; however data on the human GE anomalies are scarce. We report 5 fetal MR imaging observations with bilateral symmetric cavitations in their GE regions resembling an inverted open C shape and separating the GE itself form the deeper parenchyma. Imaging, neuropathology, and follow-up features suggested a malformative origin. All cases had in common characteristics of lissencephaly with agenesis or severe hypoplasia of corpus callosum of probable different genetic basis. From our preliminary observation, it seems that GE cavitations are part of conditions which are also accompanied by severe cerebral structure derangement.
Subject(s)
Agenesis of Corpus Callosum/embryology , Agenesis of Corpus Callosum/pathology , Magnetic Resonance Imaging/methods , Prenatal Diagnosis/methods , Telencephalon/abnormalities , Telencephalon/pathology , Female , Humans , Male , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
BACKGROUND: The observation of gait abnormalities, parkinsonism and vascular lesions in elderly patients is often reported as vascular parkinsonism (VP). However the status of striatal dopamine transporter (DAT) and the effects of brain vascular lesions on motor features and levodopa responsiveness are poorly defined. METHODS: We recorded clinical features, chronic response to levodopa and vascular risk factors in a cross-sectional cohort of consecutive elderly patients with possible Parkinson's disease (PD) or VP recruited in 20 centers in Italy. RESULTS: We included a total of 158 patients. Onset of motor symptoms was asymmetric in 93 (59%) and symmetric in 65 patients (41%). Symmetric motor onset was associated with greater disease severity. Chronic levodopa response was positive in 75 (47.8%) and negative in 82 patients (52.2%). A negative response to levodopa was associated with greater frequency of symmetric onset of motor symptoms, worst disease severity, absence of dyskinesia and greater number of vascular risk factors. Frontal lobe showed largest vascular load. Striatal DAT was normal in 48 (30.4%) and abnormal in 110 (69.6%) patients. Patients with normal DAT binding showed higher vascular load at MRI. Significant predictive factors of worst disease severity and negative response to levodopa were hypertension, vascular lesions in basal ganglia/periventricular regions, and normal DAT uptake. CONCLUSIONS: Multiple cerebral vascular lesions modify clinical presentation and severity in patients with parkinsonism and this is underlined by specific risk factors primarily hypertension. Striatal DAT assessment is helpful in identifying patients where therapy benefit is less likely.
Subject(s)
Antiparkinson Agents/therapeutic use , Cerebrovascular Disorders , Corpus Striatum/metabolism , Dopamine Plasma Membrane Transport Proteins/metabolism , Levodopa/therapeutic use , Parkinson Disease , Parkinsonian Disorders , Aged , Aged, 80 and over , Cerebrovascular Disorders/complications , Cerebrovascular Disorders/drug therapy , Cerebrovascular Disorders/physiopathology , Cohort Studies , Cross-Sectional Studies , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Parkinson Disease/drug therapy , Parkinson Disease/physiopathology , Parkinsonian Disorders/complications , Parkinsonian Disorders/drug therapy , Parkinsonian Disorders/physiopathology , Severity of Illness Index , Tomography, Emission-Computed, Single-PhotonABSTRACT
OBJECTIVE: To review the experience of performing selective feticide with bipolar cord coagulation (BCC) in complicated monochorionic (MC) twin pregnancies at a single center. METHODS: This was a retrospective analysis of BCC performed using 3-mm bipolar forceps under ultrasound control in cases complicated by twin-to-twin transfusion syndrome, selective growth restriction, discordant anomaly or twin reversed arterial perfusion sequence. RESULTS: The series comprised 118 cases with a median gestational age at the time of the procedure of 22 (range, 16-30) weeks. There were 14 (12%) intrauterine deaths of the cotwin, eight (7%) miscarriages and one (1%) termination of pregnancy. When BCC was performed before 19 weeks of gestation, the rate of miscarriage was 45%, whereas it was 3% (P < 0.001) when BCC was performed after 19 weeks. Preterm prelabor rupture of membranes (PPROM) occurred in 45 (38%) cases. The median interval between BCC and PPROM was 4 (interquartile range, 2-9) weeks. In 15 (13%) cases, PPROM occurred within 2 weeks after the procedure. Median gestational age at delivery was 34 (range, 24-41) weeks. The median birth weight was 2103 (range, 480-3875) g. Neonatal death occurred in 11 (9%) cases, and two (2%) children had severe neurologic morbidity. The overall survival rate was 71% (84/118). CONCLUSION: BCC is an effective procedure in complicated MC twin pregnancies for selective feticide or when one fetus is severely jeopardized and delivery is not yet an option. Better outcomes can be achieved when this procedure is performed after 19 weeks.
Subject(s)
Fetofetal Transfusion/surgery , Pregnancy Reduction, Multifetal/methods , Umbilical Cord/surgery , Amnion/surgery , Chorion/surgery , Diseases in Twins/mortality , Female , Fetal Death , Fetofetal Transfusion/complications , Fetofetal Transfusion/mortality , Humans , Infant, Newborn , Infant, Premature , Pregnancy , Pregnancy Reduction, Multifetal/psychology , Pregnancy, Twin , Retrospective Studies , Risk Factors , Twins, MonozygoticABSTRACT
BACKGROUND AND PURPOSE: Different and specific MR imaging patterns of lesions involving WM are widely defined in neonatal encephalopathy. The aim of this study was to describe a novel MR imaging pattern of damage characterized by the abnormal prominence of DMVs in premature and full-term neonates. MATERIALS AND METHODS: Twenty-one (11 premature and 10 full-term) neonates with MR imaging evidence of linear radially oriented fan-shaped lesions in the periventricular WM and without dural venous thrombosis were enrolled in this retrospective study. A total of 37 MR imaging examinations were performed at ages ranging from day 0 to 24 months. RESULTS: According to the appearance of linear anomalies on T2-weighted images, we identified 2 main patterns: T2 hypointense lesions without WM cavitations and T2 hypointense lesions associated with linear cysts. The first pattern was found in 17 examinations performed between 0 and 44 days of life; the second pattern was found in another 14 examinations performed between 6 days and 4 months of life. Five examinations performed between 9 and 24 months of life showed a reduction in volume and hyperintense signal intensity of the periventricular WM on T2-weighted and FLAIR images. CONCLUSIONS: Subtle linear WM lesions with the same anatomic distribution of DMVs may be evident in premature and full-term neonates without signs of major venous thrombosis, both in the acute and subacute phases. Their appearance and evolution suggest that transient DMV engorgement/thrombosis may be responsible for WM damage that can lead to a PVL-like pattern.
Subject(s)
Brain Injuries/pathology , Brain Injuries/physiopathology , Cerebral Veins/pathology , Cerebral Veins/physiopathology , Magnetic Resonance Angiography/methods , Medulla Oblongata/blood supply , Medulla Oblongata/pathology , Aging, Premature , Female , Humans , Infant, Newborn , Male , Nerve Fibers, Myelinated/pathology , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
Looking for anomalies distributed in DMV territory, we reviewed 78 fetal MR imaging examinations performed at our institution reporting unequivocal cerebral clastic lesions. We selected 3 cases, all of which had severe cardiocirculatory failure and parenchymal frontoparietal WM hemorrhagic lesions with characteristic fan-shaped distribution. Brain edema and other signs of venous hypertension were also evident. Our data suggest that in utero transient venous hypertension may be responsible for the onset of atypical frontal-located PVL.
Subject(s)
Brain Diseases/diagnosis , Cerebral Veins/abnormalities , Fetal Diseases/diagnosis , Magnetic Resonance Imaging , Prenatal Diagnosis , Adult , Female , Humans , PregnancyABSTRACT
Infantile neuroaxonal dystrophy, INAD, is a severe progressive psychomotor disorder with infantile onset and characterized by the presence of axonal spheroids throughout the central and peripheral nervous systems. A subset of INAD patients shows also brain iron accumulation which represents instead the distinctive feature of the idiopathic neurodegeneration with brain iron accumulation, NBIA. These diseases share the same causative gene, PLA2G6, encoding iPLA2-VIA, a calcium-independent phospholipase. Mutations that lead to a complete absence of protein are associated with a severe INAD profile, while compound heterozygous mutations with possibly a residual protein activity are instead associated with the less severe NBIA phenotype. Here we describe two INAD patients both with an unusually rapid disease progression and a peculiar neuroradiological presentation in one of them. Compound heterozygosity for a large intragenic deletion and a nonsense mutation was found in one of them while the other is carrying two novel splice-site mutations. Breakpoint-sequence analysis suggests a non-allelic-homologous-recombination (NAHR) event, probably underlying the rearrangement. These findings, while supporting the genotype-phenotype correlation already observed in INAD patients, provide the first sequence characterization of a genomic rearrangement in PLA2G6 gene, thus orienting the search for missing mutant alleles in PLA2G6 related diseases.
Subject(s)
Group VI Phospholipases A2/genetics , Neuroaxonal Dystrophies/genetics , Base Sequence , Child, Preschool , Group VI Phospholipases A2/physiology , Humans , Infant , Iron/metabolism , RNA Splicing , Sequence DeletionABSTRACT
BACKGROUND AND PURPOSE: Prenatal imaging data of the normal pituitary gland and in vivo information on the development of the pituitary region are lacking; however, we noticed that the pituitary stalk (PS) is visible occasionally in utero on MR images. Our main purpose was to establish the detection rate of the PS in healthy fetuses at various gestational ages (GAs) by using single-shot fast spin-echo T2-weighted images. MATERIALS AND METHODS: We selected 73 fetal cases with normal findings on prenatal MR imaging and clinical postnatal follow-up. The GA ranged between 19 and 37 weeks. The 3 planes of MR imaging sections were 4 mm thick with 1.25 x 1.25 mm in-plane resolution. Two pediatric neuroradiologists evaluated in consensus whether the PS was present as a linear isointense structure connecting the hypothalamic region with the floor of sella turcica. In those cases in which the PS was visible on the sagittal section, the angle formed by the intersection of the PS and the sellar plane (SP) was measured (PS-SP angle). RESULTS: The PS was detectable on at least 1 coronal or sagittal section from 19 to 25 weeks' GA in 30/42 fetuses (71.4% sensitivity); from 26 to 37 weeks' GA, the PS was detected in all 31 fetuses (100% sensitivity). The PS-SP angle decreased significantly with GA, being <90 degrees in all fetuses after gestational week 25. CONCLUSIONS: At the current spatial resolution of clinical prenatal MR imaging, PS can be reliably detected after 25 weeks' GA, so in case of a missing visualization, a strong suspicion of pituitary region anomaly could be raised.
Subject(s)
Fetus/anatomy & histology , Pituitary Gland/anatomy & histology , Prenatal Diagnosis/methods , Female , Humans , Male , Reference ValuesABSTRACT
INTRODUCTION: Prenatal magnetic resonance (MR) imaging is currently used to measure quantitative data concerning brain structural development. At present, morphometric MR imaging studies have been focused mostly on the third trimester of gestational age. However, in many countries, because of legal restriction on abortion timing, the majority of MR imaging fetal examination has to be carried out during the last part of the second trimester of pregnancy (i.e., before the 24th week of gestation). Accurate and reliable normative data of the brain between 20 and 24 weeks of gestation is not available. This report provides easy and practical parametric support to assess those normative data. MATERIALS AND METHODS: From a database of 1,200 fetal MR imaging studies, we retrospectively selected 84 studies of the brain of fetuses aged 20-24 weeks of gestation that resulted normal on clinical and radiological follow-up. Fetuses with proved or suspected infections, twin pregnancy, and fetuses of mothers affected by pathology that might have influenced fetal growth were excluded. Linear biometrical measurements of the main cerebral structures were obtained by three experienced pediatric neuroradiologists. RESULTS: A substantial interobserver agreement for each measurements was reached, and normative data with median, maximum, and minimum value were obtained for brain structures. CONCLUSION: The knowledge of a range of normality and interindividual variability of linear biometrical values for the developing brain between 20th and 24th weeks of gestation may be valuable in assessing normal brain development in clinical settings.
Subject(s)
Brain/embryology , Fetal Organ Maturity/physiology , Magnetic Resonance Imaging/methods , Biometry , Female , Gestational Age , Humans , Pregnancy , Prenatal Diagnosis , Reference Values , Retrospective StudiesABSTRACT
We discuss the use of magnetic resonance imaging (MRI) to reveal early fetal neurological involvement of cytomegalovirus (CMV) infection. A woman presented at 21 weeks of pregnancy with active CMV infection. Cerebral ultrasound examination had been normal. An MRI scan revealed a thickened germinal matrix, which was histologically confirmed, associated with underdevelopment of the gyri. Brain MRI proved particularly useful in identifying the findings not disclosed by routine ultrasound during pregnancy and subsequently confirmed at histology.
Subject(s)
Brain/pathology , Cytomegalovirus Infections/complications , Magnetic Resonance Imaging , Abortion, Induced , Adult , Amniotic Fluid/virology , Brain/embryology , Brain/microbiology , DNA, Viral/isolation & purification , Female , Humans , Hydrops Fetalis/microbiology , Hydrops Fetalis/pathology , Pregnancy , Pregnancy Complications, Infectious/microbiology , Pregnancy Complications, Infectious/pathology , Ultrasonography, PrenatalABSTRACT
We describe clinical and imaging features of a patient with sporadic progressive ataxia and palatal tremor (PAPT) of unknown etiology. There was hypertrophy of bilateral inferior olivary nuclei with hyperintense T2-weighted signal and mild cerebellar atrophy at brain magnetic resonance imaging. 18F-fluoro-2-desoxy-d-glucose positron emission tomography scanning (FDG-PET) showed hypometabolism in the red nucleus, external globus pallidus and precuneus while FP-CIT-SPECT imaging revealed mild and progressive loss of striatal dopaminergic terminals. Our findings suggest that in idiopathic PAPT involvement of the dentato-rubro-olivary pathway occurs along with some dopaminergic dysfunction.
Subject(s)
Basal Ganglia Diseases/physiopathology , Cerebellar Ataxia/physiopathology , Dopamine/deficiency , Myoclonic Cerebellar Dyssynergia/physiopathology , Myoclonus/physiopathology , Basal Ganglia/metabolism , Basal Ganglia/pathology , Basal Ganglia/physiopathology , Basal Ganglia Diseases/diagnostic imaging , Basal Ganglia Diseases/pathology , Cerebellar Ataxia/diagnostic imaging , Cerebellar Ataxia/pathology , Cerebellar Diseases/diagnostic imaging , Cerebellar Diseases/pathology , Cerebellar Diseases/physiopathology , Cerebellar Nuclei/metabolism , Cerebellar Nuclei/pathology , Cerebellar Nuclei/physiopathology , Diagnosis, Differential , Dopamine Plasma Membrane Transport Proteins/metabolism , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myoclonic Cerebellar Dyssynergia/diagnostic imaging , Myoclonic Cerebellar Dyssynergia/pathology , Myoclonus/diagnostic imaging , Myoclonus/pathology , Neural Pathways/metabolism , Neural Pathways/pathology , Neural Pathways/physiopathology , Olivary Nucleus/metabolism , Olivary Nucleus/pathology , Olivary Nucleus/physiopathology , Parkinson Disease/metabolism , Parkinson Disease/pathology , Positron-Emission Tomography , Red Nucleus/metabolism , Red Nucleus/pathology , Red Nucleus/physiopathology , Tomography, Emission-Computed, Single-PhotonABSTRACT
Wolf-Hirschhorn syndrome (WHS) is a rare genetic disorder, which is caused by partial deletion of the short arm of one chromosome 4. Brain magnetic resonance (MR) imaging findings are lacking. We report on brain findings in 10 children with WHS. We evaluated the MR imaging films of 10 subjects affected by WHS, which had been confirmed by genetic study. The age range at MR imaging was between 1 month and 9 years. In 9/10 cases enlargement of the third lateral ventricles was present. In 9/10 cases a global reduction of cerebral hemispheres white matter was present. In 10/10 cases diffuse thinning of the corpus callosum was visible; it was severe in 7/10 cases. In 5/10 cases small foci of T (2) hyper intense signal were visible within the subcortical white matter. In three of the six cases studied within the first year of life frontal periventricular cysts were present. In three of the four cases studied after the first year of life a squared shape of the frontal horns of the lateral ventricles was visible. The MR imaging findings reported in WHS cannot be considered pathognomonic of the syndrome, however, they may suggest WHS.