Evaluation of image-enhanced paediatric computed tomography brain examinations.

The aim of this study was to evaluate the possibility of reducing the radiation dose to paediatric patients undergoing computed tomography (CT) brain examination by using image-enhancing software. Artificial noise was added to the raw data collected from 20 patients aged between 1 and 10 y to simulate tube current reductions of 20, 40 and 60 mA. All images were created in duplicate; one set of images remained unprocessed whereas the other was processed with image-enhancing software. Three paediatric radiologists assessed the image quality based on their ability to visualise the high- and low-contrast structures and their overall impression of the diagnostic value of the image. For patients aged 6-10 y, it was found that dose reductions from 27 mGy (CTDI(vol)) to 23 mGy (15 %) in the upper brain and from 32 to 28 mGy (13 %) in the lower brain were possible for standard diagnostic CT examinations when using the image-enhancing filter. For patients 1-5 y, the results for standard diagnostics in the upper brain were inconclusive, for the lower brain no dose reductions were found possible.

A method to analyse observer disagreement in visual grading studies: example of assessed image quality in paediatric cerebral multidetector CT images.

The purpose was to demonstrate a non-parametric statistical method that can identify and explain the components of observer disagreement in terms of systematic disagreement as well as additional individual variability, in visual grading studies. As an example, the method was applied to a study where the effect of reduced tube current on diagnostic image quality in paediatric cerebral multidetector CT (MDCT) images was investigated. Quantum noise, representing dose reductions equivalent to steps of 20 mA, was artificially added to the raw data of 25 retrospectively selected paediatric cerebral MDCT examinations. Three radiologists, blindly and randomly, assessed the resulting images from two different levels of the brain with regard to the reproduction of high- and low-contrast structures and overall image quality. Images from three patients were assessed twice for the analysis of intra-observer disagreement. The intra-observer disagreement in test-retest assessments could mainly be explained by a systematic change towards lower image quality the second time the image was reviewed. The inter-observer comparisons showed that the paediatric radiologist was more critical of the overall image quality, while the neuroradiologists were more critical of the reproduction of the basal ganglia. Differences between the radiologists regarding the extent to which they used the whole classification scale were also found. The statistical method used was able to identify and separately measure a presence of bias apart from additional individual variability within and between the radiologists which is, at the time of writing, not attainable by any other statistical approach suitable for paired, ordinal data.

Effect of tube current on diagnostic image quality in paediatric cerebral multidetector CT images.

The aim of this study was to investigate the effect of tube current on diagnostic image quality in paediatric cerebral multidetector CT (MDCT) images in order to identify the minimum radiation dose required to reproduce acceptable levels of different diagnostic image qualities. Original digital scanning data (raw data) were selected retrospectively from routine MDCT brain examinations of 25 paediatric patients. All examinations had been performed using axial scanning on an eight-slice MDCT (LightSpeed Ultra, GE Healthcare). Their ages ranged from newborn to 15 years. Quantum noise was added artificially to the raw data representing dose reductions equivalent to steps of 20 mA. Patient identification information was removed. Three experienced radiologists blindly and randomly assessed the resulting images from two different levels of the brain with regard to reproduction of structures and overall image quality. Final data were evaluated using the non-parametric statistical approach of inter-scale concordance. The minimum value of tube current-time product (mAs) required to reproduce an image of sufficient diagnostic quality was established in relation to the age of the patient. The corresponding CT dose index values by volume (CTDI(vol) (mGy)) were also established. In conclusion, acceptable reproduction of low-contrast structures was possible at CTDI(vol) values down to 20 mGy (patients 1-5 years old). For acceptable reproduction of high-contrast structures, CTDI(vol) values down to 10 mGy were considered possible (patients 1-5 years old). The original image quality for patients under 6 months of age (15 mGy) was found to be inadequate for acceptable reproduction of low-contrast structures.

Progressive encephalopathy and complex I deficiency associated with mutations in MTND1.

Complex I of the oxidative phosphorylation system is composed of at least 45 subunits, seven of which are encoded by mitochondrial DNA (mtDNA). In this study we have investigated two children with complex I deficiency in muscle mitochondria. Patient 1 had cerebellar ataxia from early infancy and an abnormal MRI of the brain compatible with Leigh syndrome (LS). The course was rapidly progressive with frequent exacerbations and death at 2 years and 10 months of age. Patient 2 had a lactic acidosis in the newborn period and had a severe psychomotor developmental retardation. In her teens she developed hypertrophic cardiomyopathy and died at 26 years of age because of cardiac insufficiency. Sequencing analysis of mitochondrial encoded ND genes (MTND) showed two DE NOVO mutations in MTND1 in both patients. Patient 1 had a novel heteroplasmic G3890A mutation, R195Q. Patient 2 had a heteroplasmic G3481A mutation, E59K. The G3890A mutation in patient 1 is the first identified mutation in MTND1 in association with LS and complex I deficiency. The findings in this patient as well as in patient 2 demonstrate new clinical expressions of mutations in MTND1. The findings in patient 2 also illustrates that MTND mutations may be pathogenic even at a low percentage.

Dyskinetic cerebral palsy: a population-based study of children born between 1991 and 1998.

The aim of this study was to describe the epidemiology, aetiology, and clinical findings in dyskinetic cerebral palsy (CP)in a population-based follow-up study of children born between 1991 and 1998. Age range at ascertainment was 4 to 8 years and prevalence was 0.27 per 1000 live-births. Forty-eight children were examined (27 males, 21 females; mean age 9y, range 5-13y). Thirty-nine had dystonic CP and nine a choreo-athetotic subtype. Primitive reflexes were present in 43 children and spasticity in 33. Gross Motor Function Classification System levels were: Level IV, n= 10 and Level V, n= 28. The rate of learning disability (n= 35) and epilepsy (n= 30) increased with the severity of the motor disability. Thirty-eight children had anarthria. Peri- or neonatal adverse events had been present in 34 of 42 children born at >or=34 weeks' gestation. Motor impairment was most severe in this group. Placental abruption or uterine rupture had occurred in 8 participants and 19 of the 42 near-term/term children required assisted ventilation, compared with 1% and 12% respectively in other CP types. Neuroimaging in 39 children born at >or=34 weeks revealed isolated, late third trimester lesions in 24 and a combination of early and late third trimester lesions in seven. Dyskinetic CP is the dominant type of CP found in term-born, appropriate-for-gestational-age children with severe impairments who have frequently experienced adverse perinatal events.

Increased levels of GFAP in the cerebrospinal fluid in three subtypes of genetically confirmed Alexander disease.

GFAP levels in the CSF were highly elevated in three genetically confirmed cases of Alexander disease clinically conforming with infantile, early and late juvenile forms. No other CSF abnormalities were detected. Assay of CSF-GFAP may prove to be a rapid and cost-effective screening test in clinical variants of Alexander disease and an indicator of GFAP gene mutations.

A method of predicting the image noise in paediatric multi-slice computed tomography images.

The purpose of this study was to develop an equation with which to determine the tube current to be used in order to obtain a certain image noise level for differently sized children undergoing multi-slice computed tomography examination. The relationship between image noise and detector dose for different examination protocols was established for a LightSpeed Ultra, an eight slice CT from GEMS, using homogeneous water phantoms of different sizes. Three different anatomical areas (head, thorax and abdomen) were studied in 111 patients between 0 and 17 y of age. The mean ratio between the calculated and the measured noise in patient images was established for the different areas. Head examinations showed the best correlation (measured-to-calculated noise ratio = 1.01). In the thorax, the calculated noise was generally higher than the measured noise (ratio = 0.74), and in the abdomen, the opposite result was found (ratio = 1.20).

Leigh syndrome with cytochrome-c oxidase deficiency and a single T insertion nt 5537 in the mitochondrial tRNATrp gene.

We report a nine-year-old boy with the features of Leigh syndrome (LS) and a severe cytochrome-c oxidase (COX) deficiency with a single thymidine insertion at nucleotide position 5537 (T 5537i) in the tRNA Trp gene of mitochondrial DNA. During infancy the boy was irritable and hypotonus was noticed. Early motor development was delayed, although mental development seemed normal until eight months of age. Early neurological signs were nystagmus, hypertonus and optic atrophy. Severe seizures and mental retardation developed subsequently. Major findings on neuroradiological investigation were from the brainstem, thalami and white matter compatible with LS. Spectrophotometric analysis of skeletal muscle mitochondria showed a profound COX deficiency and a marked complex I deficiency. Enzyme-histochemical analysis showed reduced COX activity in the majority of the muscle fibres. There were no ragged red fibres. The T 5537i mutation was found in a high proportion (> 95 %) in blood, liver and muscle tissue of the patient and in blood of the patient's mother (81 %). This mutation has previously been described in one family in which one child had a very high proportion of the T 5537i mutation and clinical features of LS. We conclude that, although mtDNA mutations are considered to be rare in LS with COX deficiency, the T 5537i mutation should be screened for in cases of LS with COX deficiency when SURF1 gene mutations have been excluded, especially when complex I activity is also decreased.

Dysarthria, progressive parkinsonian features and symmetric necrosis of putamen in a family with painful lipomas (Dercum disease variant).

We describe painful subcutaneous lipomatosis in four members of a two-generation family. Lipomas appeared in adulthood, were circumscribed, painful on touch and mainly localized to the trunk and proximal parts of the extremities. The disorder was associated with dysarthria, visual pursuit defect and progressive dystonia. MRI showed bilateral increasing cystic lesions in the basal parts of the putamen. No other abnormalities were detected. The lesions corresponded well with the clinical presentation in the patients. Investigation for mitochondrial disease with muscle biopsy and mitochondrial DNA gave normal results. No consistent biochemical changes were found. The disorder in this family was considered to differ from MERRF with lipomatous lesions and multiple symmetric lipomatosis but compatible with a Dercum disease variant.

Clinical characteristics of children with cerebral white matter abnormalities.

The rapidly expanding use of magnetic resonance imaging (MRI) in children with neurological impairments of unknown aetiology has revealed a large number of children with abnormalities of the cerebral white matter, some with leukodystrophy-like white matter abnormalities on MRI, but non-progressive in clinical presentation and course. The aim of this study was to investigate the clinical and neuroradiological characteristics of 26 children with white matter abnormalities of unknown origin and to find diagnostic clues or indicators of progressive versus nonprogressive disease. The typical child with white matter abnormalities was characterized by onset of symptoms within the first year of life, most often presenting as general developmental delay and hypotonia. Later-appearing signs were spasticity and ataxia and as a rule severe learning and motor disabilities. Serious ophthalmological signs were frequently seen. Perinatal adverse events were rare, infectious aetiologies not indicated but prenatal stigmata relatively common. The clinical course was progressive in 11 children and non-progressive in 15. Late onset presentation was associated with a progressive course whereas prenatal stigmata and asymmetrical white matter lesions only were found in children with a non-progressive disorder. The MRI showed three main patterns: a) a generalized increase of the T2 signal of the white matter in 12 children, b) a bilateral, symmetric but not generalized abnormality in nine and c) asymmetric, focal or multifocal pathology in five. Useful information as to clinical entities and course was obtained from the combined clinical and radiological assessment. A precise nosological diagnosis could be made in six cases. The study showed that white matter abnormalities in children constitute a heterogeneous group of rare and 'anonymous' conditions, motivating collaborative studies for further clarification of background and management.

The clinical and morphologic spectrum of optic nerve hypoplasia.

PURPOSE: The purpose of this study was to characterize the clinical and morphologic spectrum of all children referred for optic nerve hypoplasia to a tertiary referral hospital in Sweden during a 9-year period. SUBJECTS AND METHODS: A retrospective review was undertaken of the charts of 117 children (age range, 0.25-16 years), treated at the Children's Hospital, Göteberg between 1988 and 1996, after the diagnosis of optic nerve hypoplasia. Ocular fundus morphologic condition was evaluated by digital image analysis of fundus photographs in 50 children, and neuroimaging was performed in 57 children. RESULTS: Of the 117 children with optic nerve hypoplasia, 66 (56%) were boys and 51 (44%) were girls. Preterm birth occurred in 24 (20%), and 14 (12%) were born small for gestational age. Additional diagnoses, such as fetal alcohol syndrome, septo-optic dysplasia, perinatal adverse events, and neuropsychiatric disorders, were made in 88%; 7% had unilateral optic nerve hypoplasia. Most of the children had small optic disc, cup, and neuroretinal rim areas, as well as retinal vascular abnormalities; 75% were visually impaired, and a high incidence of nystagmus and strabismus was found among these children. CONCLUSION: This study indicates that optic nerve hypoplasia has a wide clinical and morphologic spectrum and is associated with a broad range of disorders of the central nervous system. It is suggested that differences in the etiology and timing of the lesion as well as associated lesions may explain this spectrum of optic nerve hypoplasia in children.

Optic nerve hypoplasia with isolated tortuosity of the retinal veins: a marker of endocrinopathy.

OBJECTIVE: To investigate whether children with optic nerve hypoplasia and pituitary hormone insufficiencies have specific ocular fundus characteristics that may facilitate early diagnosis and treatment. DESIGN: From May 15, 1995, through December 15, 1997, 17 children (8 girls and 9 boys, aged 0.3 to 13 years) with optic nerve hypoplasia were referred to the Department of Pediatric Ophthalmology, Children's Hospital, Göteborg, Sweden, and divided into 2 groups dependent on the presence (n = 8) or absence (n = 9) of pituitary deficiency. Morphological characteristics of the ocular fundus were evaluated by digital image analysis of fundus photographs, and the morphological characteristics of the brain structures were studied by magnetic resonance imaging. RESULTS: An isolated venous tortuosity noted among the children with optic nerve hypoplasia and endocrinopathy was the morphological ocular fundus variable that discriminated between the 2 groups of patients with optic nerve hypoplasia. Both groups of children demonstrated significantly reduced optic disc, cup, and neuroretinal rim area and few vascular branching points. CONCLUSION: Optic nerve hypoplasia with isolated tortuosity of the retinal veins may potentially help the ophthalmologist in identifying children who should undergo a thorough diagnostic workup of endocrine function.

Diagnostic value of magnetic resonance imaging and planimetric measurement of optic disc size in confirming optic nerve hypoplasia.

PURPOSE: This study set out to evaluate magnetic resonance imaging (MRI) and measurement of optic disc size as diagnostic tools for confirming the diagnosis of optic nerve hypoplasia (ONH) in children with impaired growth. METHODS: MRI was performed to study the size of the intracranial visual pathways, and image analysis measurements of fundus photographs were performed to determine the size of the optic disc. Results from these investigations were compared with those using the gold standard for diagnosis of ONH, which was the clinical eye examination (visual function, ophthalmoscopic signs, or both). Forty children (median age, 9 years; range, 3 to 19 years) with impaired growth were included in the study. RESULTS: The prevalence of ONH among the children was 15%. MRI classification of the visual pathways had a higher positive predictive value than image analysis measurement of the optic disc size (1.0 vs 0.6). CONCLUSIONS: MRI is a good tool for confirming the diagnosis of ONH and may thus facilitate early detection. On the other hand, a small optic disc per se is not a definite indicator of ONH but should encourage further investigation with MRI, especially if there is a clinical suspicion of ONH.

Intractable epilepsy in a population-based series of mentally retarded children.

PURPOSE: The characteristics of intractable epilepsy were analyzed in a population-based study of active epilepsy in mentally retarded children aged 6-13 years. METHODS: Diagnostic registers, EEG laboratory registers, and registers for the Education of the Subnormal were searched. Medical files were scrutinized. Clinical examinations and interviews with parents and caregivers or both were performed. EEG recordings, computed tomography (CT) and magnetic resonance imaging (MRI) of the CNS were reevaluated. RESULTS: Forty-five percent (44 of 98) of the children with mental retardation (MR) and active epilepsy had intractable seizures, defined as one or more seizures every day or week. The median age at onset was 0.8 years, as compared with 3.0 years for those with controlled epilepsy. Predictive factors for frequent seizures were the number of seizure types, severe MR, status epilepticus (SE) and tonic seizures. Epileptiform EEG activity was present in 91%, and focal activity in 65%. Brain lesions were detected on CT and MRI in 70%, with generalized lesions in 60%. Concurrent focal epileptiform activity and focal brain lesions on CT/MRI were detected in 26%. The percentages and prevalence rates for infantile spasms (IS) and Lennox-Gastaut syndrome (LGS) were 18% (0.25 in 1,000) and 7% (0.06 in 1,000), respectively. One of 8 children with IS had had previous neonatal seizures, 3 had SE and 1 later developed LGS. CONCLUSIONS: Children with MR and intractable epilepsy have a high frequency of severe MR and additional major neuroimpairments. EEG recordings frequently showed focal changes despite generalized lesions in neuroradiology.

Midline brain lesions in children with hormone insufficiency indicate early prenatal damage.

The relationships between midline brain morphology, anterior visual pathway morphology and hormonal status in children with impaired growth were studied. Intracranial morphology was studied by magnetic resonance imaging in 47 children (14F, 33M), median age 9.7y (range 2.6-18.7y) undergoing growth hormone treatment (GH; 0.1 U/kg/d). They were chosen to represent various birth sizes and a spectrum of hormone insufficiencies. There was a relationship between GH secretion and the morphology of the neurohypophysis, the pituitary stalk and the anterior visual pathways, i.e. the greater the GH insufficiency, the more abnormal were these structures. The children with anterior visual pathway abnormalities had the lowest GH levels and the smallest adenohypophysis. The association between abnormalities of the anterior visual pathways and the hypothalamo-pituitary structures may reflect a common prenatal neural damage in embryologically and anatomically closely related structures.

Computed tomography and single-photon emission computed tomography as diagnostic tools in acquired brain injury among children and adolescents.

Twenty children with acquired brain injuries were investigated with CT and SPECT. The findings were related to the clinical outcome judged at discharge following acute care after the injury and at follow-up 5 years later. The abnormalities that were found were classified for each lobe on a scale ranging from 0 (normal) to 5 (severe abnormality). The patients were divided into two groups showing mild and severe injury. CT and SPECT revealed similar results in the patients with severe injury, but in the group of mildly injured children the number of affected lobes and scores indicated by SPECT were significantly higher than those indicated by CT. SPECT also differentiated more effectively between the two outcome groups. This supports the hypothesis that SPECT could be used as an instrument to objectivise minor sequelae and that SPECT and CT are both useful methods for forecasting outcome.

Disorders of the cerebral white matter in children. The spectrum of lesions.

The use of magnetic resonance imaging (MRI) has resulted in the detection of an increasing number of children with an apparently leukodystrophic white matter. Laboratory tests and the clinical presentation, however, often do not correspond to any known entity and the course is sometimes not progressively deteriorating. Such children with white-matter changes and no known diagnosis were the subject of this Swedish multicentre study, in which MRI findings and clinical data from 100 children considered to have white-matter abnormalities were assessed during the period 1992-1995. At re-evaluation of MR images by an established "white-matter group" of neuroradiologists, paediatric neurologists, neurologists and neurochemists, the MRI signal of the white matter was considered normal in eleven children and eleven had mainly a grey matter affection. Of the remaining 78 children with white matter abnormalities, a diagnosis was found in 32, but in 46 children no diagnosis could be established. A progressive downhill course characterised 17, probably representing hitherto undefined types of leukodystrophies. Five children had a relapsing-remitting course, and in 11 it was difficult to establish whether the course was progressive or stationary. The disease was non-progressive in 13. This group of non-leukodystrophic white-matter changes obviously represents maldevelopments of myelin formation, thus dys- or hypomyelination rather than demyelination.

Verbal and non-verbal function of children with right- versus left-hemiplegic cerebral palsy of pre- and perinatal origin.

Eighteen children with right- and 13 with left-sided congenital hemiplegia were compared with 19 normal age-matched controls for verbal and non-verbal function. CT scans were obtained from 27 of the 31 hemiplegic children. The two hemiplegic groups were impaired in non-verbal function compared with controls. The right-hemiplegic group was more impaired in verbal function than the left-hemiplegic group and controls; however, impairments were restricted to the girls in the right-hemiplegic group. The results are discussed in terms of cerebral plasticity and functional reorganisation of cognitive functions after an early unilateral injury. It is argued that girls with left-hemisphere lesions may be more limited in cerebral plasticity than boys.

Nonionic contrast media in pediatric CT. A comparative study of intravenous use of iopentol and iohexol.

In pediatric radiology there is a great demand for a safe contrast medium. In this pediatric CT trial, the safety, tolerability and efficacy of 2 nonionic contrast media, iopentol (Imagopaque) and iohexol (Omnipaque), were evaluated. The study was performed as a double-blind, randomized, parallel trial, with 55 children receiving iopentol (300 mg I/ml) and 55 receiving iohexol (300 mg I/ml). The dose injected was 2 ml/kg b.w. with an upper limit of 100 ml. Blood pressure and pulse rate were recorded. Adverse events were recorded by observation of the patients up to 24 hours after the examination. No clinically or statistically significant changes occurred. Seven adverse events other than discomfort (2 in the iopentol group and 5 in the iohexol group) were reported. The overall quality of CT enhancement was good or excellent in all cases. The results support the use of iopentol as an alternative to iohexol in pediatric CT examinations.