Biomedical subjects
Publications and source records attributed to S Blaser.
P250R mutation in the FGFR3 gene also known as Muenke syndrome is associated with coronal craniosynostosis, sensorineural deafness, craniofacial, and digital abnormalities. We report a family with this mutation associated with sudden death in an affected newborn, most probably due to upper airway obstruction.
We report a fetus with exencephaly diagnosed by fetal magnetic resonance imaging (MRI) at 17 weeks of gestation. Fetal ultrasound performed at 13 and 17 weeks of gestation suggested occipital encephalocele. However, the fetal MRI done at 17 weeks of gestation showed exencephaly and suggested amniotic bands as the cause. By providing early and precise information regarding the abnormality and the possible etiology, the fetal MRI enabled us to provide the couple and their families with accurate information regarding the low recurrence risk of this condition.
INTRODUCTION: We report three cases of brain malformation presenting with a midline mass of dysplastic cortex that we have termed "brain in brain" malformation. RESULTS: The three cases have holoprosencephalic features, including bilateral hemispheric continuity across the midline, single ventricle, midline facial defect and missing olfactory bulbs. All three cases have a midline conglomerate mass of deeply infolded, cortex-lined fissures with major arterial branches, heterotopia and large amount of white matter. The dysplastic mass of cortex and white matter extended into the third ventricle. The cortex and white matter of the dysplastic lesion was continuous with the cortex and white matter, respectively, of the cerebral hemispheres. CONCLUSION: The midline "brain in brain" malformations have some similarities to subcortical heterotopia and extracerebral glioneuronal heterotopia. However, the continuity with the cerebral hemispheres and extension into the ventricle were not reported in subcortical or glioneuronal heterotopia. The common involvement of the midline cortex and extension into the third ventricle implied an anterior segmental prosencephalic abnormality (prosomeres 5/6). However, its pathogenesis remains to be explained.
BACKGROUND: Alexander disease is most commonly associated with macrocephaly and, on MRI, a leukoencephalopathy with frontal preponderance. The disease is caused by mutation of the GFAP gene. Clinical and MRI phenotypic variation have been increasingly recognized. METHODS: The authors studied seven patients with Alexander disease, diagnosed based on mutations in the GFAP gene, who presented unusual MRI findings. The authors reviewed clinical history, MRI abnormalities, and GFAP mutations. RESULTS: All patients had juvenile disease onset with signs of brainstem or spinal cord dysfunction. None of the patients had a macrocephaly. The MRI abnormalities were dominated by medulla and spinal cord abnormalities, either signal abnormalities or atrophy. One patient had only minor cerebral white matter abnormalities. A peculiar finding was the presence of a kind of garland along the ventricular wall in four patients. Three patients had an unusual GFAP mutation, one of which was a duplication mutation of two amino acids, and one an insertion deletion. CONCLUSION: Signal abnormalities or atrophy of the medulla or spinal cord on MRI are sufficient to warrant DNA analysis for Alexander disease. Ventricular garlands constitute a new sign of the disease. Unusual phenotypes of Alexander disease are found among patients with late onset and protracted disease course.
Maple syrup urine disease (MSUD) is a metabolic disorder due to a block in the decarboxylation step in the catabolic pathways of the branched-chain amino acids (BCAAs). We describe an atypical presentation in an infant male. The patient presented with psychomotor retardation, profound hypotonia and elevated plasma levels of BCAAs, but no elevation of alloisoleucine. Cranial magnetic resonance imaging showed prominent diffuse CSF spaces, delayed myelin maturation and symmetrical signal abnormality within the globi pallidi, midbrain, dorsal pons and medulla. The cerebellar white matter was specifically spared. A mitochondrial disorder was suggested. After correction of feeding problems with G-tube feeds, his high BCAAs persisted and, on fourth analysis, alloisoleucine was seen. Subsequent fibroblast enzyme and mutation analysis confirmed MSUD due to E(1)-alpha subunit deficiency. After starting dietary treatment, there was no significant improvement in his hypotonia or his psychomotor development. However, the high signal within the globi pallidi had resolved. MSUD may have diverse clinical presentations, and should be considered in children who present with chronic psychomotor delay but no acute encephalopathic episodes. BCAA levels may not be very high, alloisoleucine may not always be detected in MSUD even with severe enzyme deficiency, and imaging may be misleading if seen in the chronic phase only.
BACKGROUND AND PURPOSE: The dural venous sinuses in neonates differ from those in adults or older children in that the caliber of venous sinuses is smaller and there is skull molding. The aim of this retrospective study is to evaluate the presence of flow gaps in venous sinuses in neonates on 2D time-of-flight (TOF) MR venography (MRV). METHODS: Fifty-one neonates underwent coronal 2D TOF MRV. Nine also had CT venography (CTV) for comparison. In 1 neonate, a further 2D TOF MRV was performed in the sagittal plane; in another neonate, images were captured in the axial plane; and in another, a further coronal TOF MRV with shorter echo time was performed. RESULTS: Flow gap was seen in the posterior aspect of the superior sagittal sinus in 35 of 51 (69%). Focal narrowing of the superior sagittal sinus, in the region of convergence of lambdoid sutures, was detected in 7 of 51 (14%). The right and left transverse sinuses demonstrated flow gap in 13 of 51 (25%) and 32 of 51 (63%) respectively. There was normal filling of contrast on CTV in the superior sagittal sinus, transverse sinus and sigmoid sinus in those cases with flow gap detected on coronal 2D TOF MRV. Right, left, and codominance of the transverse sinuses are as follows: 32 of 51 (63%), 5 of 51 (10%), and 14 of 51 (27%), respectively. The right and left sigmoid sinuses demonstrated flow gap in 7 of 51 (14%) and 8 of 51 (16%), respectively, and the left sigmoid sinus was absent in 1 of 51 (2%). CONCLUSION: The high proportion of flow gap in the venous sinuses of neonates, particularly of the superior sagittal sinus, could be attributed to the smaller caliber venous sinuses, slower venous flow, and skull molding.
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OBJECTIVE: To report on the prenatal ultrasound findings in fetuses with lissencephaly associated with Miller-Dieker syndrome (MDS) and to compare these findings with those of magnetic resonance imaging (MRI). METHODS: Cases of MDS confirmed by postnatal chromosome microdeletion analysis were identified through review of patient records. Prenatal ultrasound scans were reviewed retrospectively by two radiologists. For cerebral cortical development, the Sylvian, parieto-occipital and calcarine fissures, and the cingulate sulcus and sulci over the cerebral convexity were evaluated. If one or more of these fissures or sulci were not visualized at the expected gestational age or their appearance was abnormal for gestational age, cortical development was considered delayed. Prenatal and postnatal MRI examinations were reviewed by a pediatric neuroradiologist. RESULTS: There were seven cases of MDS. In three cases, the prenatal diagnosis of agyria/lissencephaly was prospectively suspected by ultrasound at 23, 26 and 30 weeks, and subsequently confirmed by prenatal MRI. When we retrospectively reviewed the prenatal ultrasound scans of all fetuses, all had delayed cortical development identified on ultrasound performed after 23 weeks' gestation. In all cases the Sylvian fissure was abnormal on both ultrasound and MRI. In one fetus, a normal cortical appearance for gestational age was seen at the initial 20-week ultrasound examination, but delayed cortical development was identified at a 24-week scan. Mild ventriculomegaly was seen in six fetuses and dysgenesis of the corpus callosum in one. Extracranial abnormalities were detected in five fetuses. Delayed cortical development was seen in two fetuses with mild ventriculomegaly, but no other fetal anomalies. CONCLUSIONS: In fetuses with MDS, delayed cortical development can be suspected on ultrasound as early as 23 weeks' gestation. This finding warrants further investigations including MRI and FISH analysis for chromosome 17p13.3 deletion.
INTRODUCTION: The past decade has been witness to significant diminution in incision size and placement for pediatric cochlear implantation at our institution. Furthermore, the orientation of the long axis of the implant relative to the skull base plane has generally evolved from a retro-verted to ante-verted direction to accommodate the ear level receiver stimulator and the new minimal access technique. OBJECTIVE: To characterize the cosmetic, functional and clinical implications of this evolution in cochlear implant positioning by means of a patient satisfaction survey. METHODS: A survey of patient satisfaction was administered to 100 cochlear implant recipients or their parents. The survey elicits the patient's level of satisfaction with respect to implant position and functional limitations. In addition, the angle formed by the long axis of the implant and the skull base plane (implant angle) was determined from lateral skull radiographs to detect the temporal evolution in implant positioning. RESULTS: Analysis of the radiographs revealed an implant angle of 65.4-125 degrees in patients implanted prior to 1997, an implant angle of 56.3-87.5 degrees in patients implanted from 1997 to 2001, and an implant angle of 35.1-78.1 degrees after 2002. In spite of this evolution in positioning, the patient satisfaction survey did not reveal any change in incidence of cosmetic, functional or clinical problems. DISCUSSION: The significant changes in incision and implant positioning represent a technical evolution in pediatric cochlear implant surgery. The fact that patients have been consistently satisfied over time suggests that the cosmetic, functional and clinical implications are minimal.
Horizontal gaze palsy associated with progressive scoliosis (HGPS) is a rare autosomal recessive condition that has been recently mapped to a 30-cM region on chromosome 11q23-25. In this report, we describe a consanguineous family in which three of five sibs are affected with HGPS. In two of the affected sibs, there was significant cognitive delay in addition to congenital horizontal gaze palsy and childhood onset scoliosis. In all three affected sibs, magnetic resonance imaging (MRI) scans revealed brainstem hypoplasia, a finding that has recently been associated with HGPS. Clinical examination of the family showed no significant dysmorphic features, while karyotyping, EMG, nerve conduction, and muscle biopsies were unrevealing. Homozygosity mapping was performed to narrow the disease locus on 11q23-25. A recombination event was observed in one affected sib between markers D11S1345 and D11S4464, which further refined the region to a 9-cM interval. Since the MRI results provide support for the theory that maldevelopment of neurons in the abducens nuclei and caudal longitudinal fascicle is the cause for HGPS, we speculate on the existence of a gene in this 9-cM interval on chromosome 11q23, which is critical for brainstem development.
Agenesis of the parotid gland is extremely rare with only few cases reported in the medical literature. This entity can be important to diagnose as occasionally the normal parotid gland can be mistaken for a tumor due to the facial asymmetry. In this article, we present the case of an isolated unilateral parotid gland agenesis in a young child. The entity is discussed along with important associated conditions that should be ruled out. These include amongst others first and second branchial arch anomalies, as well as the Levy-Hollister or lacrimo-auriculo-dentodigital syndrome.
BACKGROUND AND PURPOSE: To date, the demonstration of Rosenthal fibers on brain biopsy or autopsy specimens is considered a prerequisite for a definitive diagnosis of Alexander disease. We initiated a multiinstitutional survey of MR abnormalities in both presumed and confirmed cases of Alexander disease to assess the possibility of an MR-based diagnosis. METHODS: MR imaging studies in three patients with an autopsy-based diagnosis of Alexander disease were analyzed to define MR criteria for the diagnosis. These criteria were then applied to 217 children with leukoencephalopathy of unknown origin. RESULTS: Five MR imaging criteria were defined: extensive cerebral white matter changes with frontal predominance, a periventricular rim with high signal on T1-weighted images and low signal on T2-weighted images, abnormalities of basal ganglia and thalami, brain stem abnormalities, and contrast enhancement of particular gray and white matter structures. Four of the five criteria had to be met for an MR imaging-based diagnosis. In a retrospective analysis of the MR studies of the 217 patients, 19 were found who fulfilled these criteria. No other essentially new MR abnormalities were found in these patients. In four of the 19 patients, subsequent histologic confirmation was obtained. The clinical symptomatology was the same in the patients with and without histologic confirmation and correlated well with the MR abnormalities. MR abnormalities were in close agreement with the known histopathologic findings of Alexander disease. CONCLUSION: The defined criteria are sufficient for an in vivo MR imaging diagnosis of Alexander disease; only in atypical cases is a brain biopsy still necessary for a definitive diagnosis.
The presence and role of septin proteins in yeast is well documented, but there is a growing appreciation for this family of proteins beyond yeast and extending to human cells. In this report we present the characterization and comparison of two highly similar human septin genes, PNUTL1 and PNUTL2. We compare the exon/intron structure of both genes, the steady-state mRNA levels in tumor cell lines and adult organs, the conceptual translation products from alternatively processed mRNAs and the development of specific immunologic reagents distinguishing either PNUTL1 or PNUTL2. The results illustrate a remarkable similarity between the two genes and their protein products while identifying specific differences in mRNA expression patterns. A summary of the described functional roles for mammalian septins is discussed along with an attempt to assimilate the alternative nomenclature existing for the same human septins, such as references to PNUTL1 and PNUTL2 as hCDCrel-1 and hCDCrel-2, respectively. The characterization of PNUTL1 and PNUTL2 represents a fundamental step in completing the characterization of the entire family of human septin genes.
Preoperative radiologic studies to detect root avulsions of the brachial plexus caused by birth trauma are considered useful in assisting with surgical planning for reconstruction. In this study, the predictive value of computed tomographic (CT) myelography in detecting nerve root avulsions at our institution was determined. Sixty-three consecutive patients with an obstetrical brachial plexus palsy who had had both preoperative CT myelography and reconstructive surgery were selected. All CT myelograms were analyzed post hoc by a single neuroradiologist in a manner blind to the surgical findings. At each root level of the brachial plexus, the presence of a pseudomeningocele was noted along with the presence or absence of rootlets within each identified pseudomeningocele. Extraforaminal root avulsions later determined at surgery were reviewed by a single surgeon in a manner blind to the radiographic results. Surgical and radiographic findings were then compared at each corresponding root level. A total of 281 roots were examined. The sensitivity, specificity, positive predictive value, and likelihood ratio for root avulsions with pseudomeningoceles were 0.63, 0.85, 0.40, and 4.2, respectively. For pseudomeningoceles for which rootlets traversing the sac could not be identified, these values were 0.37, 0.98, 0.74, and 18.5, respectively. The presence of pseudomeningoceles with or without rootlets was not a sensitive indicator of root avulsions. Root avulsions were better predicted by identifying the absence of rootlets in a pseudomeningocele. This absence on CT myelography may be used to suggest an extraforaminal root avulsion due to its high specificity and high likelihood ratio.
We report a female patient with congenital toxoplasmosis who presented with hydrops fetalis and cerebral abnormalities, detected on fetal ultrasound. Following prenatal treatment, the hydrops fetalis resolved and at four months of age she has normal growth and development. This case emphasizes the potential good prognosis in cases with congenital toxoplasmosis detected and treated prenatally.
Neurofibromatosis type 1 is the commonest of the phakomatoses with a prevalence of 1 in 3-4000. In common with most of the other phakomatoses it is a genetic disorder with typical dermatological manifestations. Many organ systems can be affected but brain, spine, cranial nerve and peripheral nerve involvement is frequent. In this review we will describe the central nervous system manifestations of neurofibromatosis type 1 and discuss some of the controversies raised by investigating children with this disorder.
OBJECTIVES: The purpose of this study was to investigate the natural history of the high signal intensities shown on long TR sequences-neurofibromatosis type 1 bright objects (NBO)-in children with neurofibromatosis type 1 (NF1). We have paid particular attention to the development of tumors in these areas of abnormality. METHODS: During a 12-month period in 1992 to 1993, 46 children with clinically proven NF1 had a magnetic resonance (MR) examination at our institution. These were reviewed along with any previous or subsequent MR examinations that had been performed. We recorded the number, volume, and distribution of the abnormal high signal intensities and their change with time when serial examinations were performed. RESULTS: NBO were found in 93% of 46 children with NF1 on the original cross-sectional study. The most common anatomic sites were the globus pallidus (30.4%), cerebellum (23.5%), and midbrain (16.2%). The number and volume of NBO varied significantly with age. NBO were uncommon in children younger than 4 years but were very common and extensive between 4 to 10 years. A significant reduction in the number and volume of NBO was demonstrated in children older than 10 years as shown on both the cross-sectional and longitudinal portions of the study. Eight brain tumors (nonoptic pathway) were demonstrated in the 46 children (17%) with 1 child having two tumors. Only 1 child had symptoms referable to the tumor at the time of diagnosis. Five tumors developed in NBO that were documented on serial MR examinations. All those cases developed in children aged 7 to 12 years, and all these children had higher than average numbers and volumes of NBO. CONCLUSIONS: NBO occur commonly in children with NF1 and are most prevalent between the ages of 4 and 10. We have shown a high frequency of brain tumors in our children with NF1, but the majority of these were asymptomatic. We have demonstrated proliferative change NBO in 11% of 46 children. Most NBO regress with age and seem to be benign, however, young children with a large number and volume of NBO should be followed closely with regular MR examinations because of an increased risk of proliferative change. neurofibromatosis type 1, magnetic resonance, tumor, astrocytoma, childhood.
The case of a neonate with a large vertex cephalocele is presented. The anatomical features of this anomaly were evaluated by means of magnetic resonance imaging and magnetic resonance angiography. Fusion of the thalami, dysgenesis of the corpus callosum, and failure of adequate formation of the interhemispheric fissure were characteristics of the major cerebral anomalies associated with the cephalocele. The absence of a falx in the midline, a split configuration of the superior sagittal sinus, and a dysgenetic tentorium with a concomitant abnormal venous drainage pattern were found in association with a large dorsal cyst. Repair of the anomaly was undertaken on the 3rd postnatal day. A cerebrospinal fluid shunt was required to treat hydrocephalus on Day 30. The child is well at age 3 years, but with significant developmental delay. The pathogenesis of this vertex cephalocele relates to semilobar holoprosencephaly and dorsal cyst formation. In addition, a disturbance in the separation of the diencephalic portion of the neural tube from the surface ectoderm or skin during the final phases of neurulation had occurred to help create the large cephalocele. Detailed preoperative imaging studies and awareness of the embryology and anatomy of this lesion facilitated the repair of the cephalocele. The prognosis of the child is determined not only by the presence of hydrocephalus, but also by the number of associated major cerebral anomalies. Options for treatment are discussed.