Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study.

OBJECTIVE: To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. DESIGN: Retrospective study with a case series. SETTING: Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. PARTICIPANTS: 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. MAIN OUTCOME MEASURES: Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. RESULTS: Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. CONCLUSION: Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem.

Neural correlates of progressive reduction of bradykinesia in de novo Parkinson's disease.

BACKGROUND: A progressive reduction in the speed and amplitude of repetitive action is an essential component of bradykinesia, which is called sequence effect (SE). Because SE is specific to Parkinson's disease (PD) and is suggested to be associated with motor arrest, its features are of great interest. The aim of this study was, for the first time, to find the neural correlates of SE and to demonstrate whether dopaminergic deficit is correlated with SE. METHODS: We enrolled 12 patients with de novo PD at a tertiary referral hospital. Correlations between SE severity and alterations in gray and white matter were studied. The association between severity of the SE and striatal dopaminergic deficits was also analyzed. RESULTS: There was a significant negative correlation between the volumetric changes in the anterior cingulate cortex (ACC) and the inferior semilunar lobule of the cerebellum and the degree of SE. There was a significant correlation between the long association fibers (the superior longitudinal fasciculus, the uncinate fasciculus, and the inferior fronto-occipital fasciculus) connecting the frontal lobes to the temporal, parietal, and occipital lobes and SE. There was a significant negative correlation between SE in the more affected hand and the caudate dopamine transporter binding in the more affected hemisphere. CONCLUSIONS: Our results suggest that the ACC and the cerebellum (inferior semilunar lobule) are associated with the severity of SE. Taken together with DTI findings, the present study proposes that ACC may have an important role. Our data show that the caudate dopaminergic activity may be related to SE.

Gestational iron deficiency differentially alters the structure and function of white and gray matter brain regions of developing rats.

Gestational iron deficiency (ID) has been associated with a wide variety of central nervous system (CNS) impairments in developing offspring. However, a focus on singular regions has impeded an understanding of the CNS-wide effects of this micronutrient deficiency. Because the developing brain requires iron during specific phases of growth in a region-specific manner, we hypothesized that maternal iron deprivation would lead to region-specific impairments in the CNS of offspring. Female rats were fed an iron control (Fe+) or iron-deficient (Fe-) diet containing 240 or 6 µg/g iron during gestation and lactation. The corpus callosum (CC), hippocampus, and cortex of the offspring were analyzed at postnatal day 21 (P21) and/or P40 using structural and functional measures. In the CC at P40, ID was associated with reduced peak amplitudes of compound action potentials specific to myelinated axons, in which diameters were reduced by ∼20% compared with Fe+ controls. In the hippocampus, ID was associated with a 25% reduction in basal dendritic length of pyramidal neurons at P21, whereas branching complexity was unaffected. We also identified a shift toward increased proximal branching of apical dendrites in ID without an effect on overall length compared with Fe+ controls. ID also affected cortical neurons, but unlike the hippocampus, both apical and basal dendrites displayed a uniform decrease in branching complexity, with no significant effect on overall length. These deficits culminated in significantly poorer performance of P40 Fe- offspring in the novel object recognition task. Collectively, these results demonstrate that non-anemic gestational ID has a significant and region-specific impact on neuronal development and may provide a framework for understanding and recognizing the presentation of clinical symptoms of ID.

Osmotic demyelination syndrome: central pontine myelinolysis and extrapontine myelinolysis.

Osmotic demyelination syndrome (ODS) refers to central pontine myelinolysis and extrapontine myelinolysis. These disorders are characterized by insults to regions of the brain with anatomical features predisposing white matter tracts to myelin injury in the setting of osmotic disturbances and their attempted correction. Occurring independently or in combination, central pontine myelinolysis and extrapontine myelinolysis share a characteristic timing of onset, but distinct clinical features. Imaging features demonstrate characteristic findings that suggest ODS, but must be correlated with clinical features. Once thought to be universally devastating, ODS currently can have a variable clinical outcome.

Multi-delay arterial spin labeling perfusion MRI in moyamoya disease--comparison with CT perfusion imaging.

OBJECTIVES: To present a multi-delay pseudo-continuous ASL (pCASL) protocol that offers simultaneous measurements of cerebral blood flow (CBF) and arterial transit time (ATT), and to study correlations between multi-delay pCASL and CT perfusion in moyamoya disease. METHODS: A 4 post-labeling delay (PLD) pCASL protocol was applied on 17 patients with moyamoya disease who also underwent CT perfusion imaging. ATT was estimated using the multi-delay protocol and included in the calculation of CBF. ASL and CT perfusion images were rated for lesion severity/conspicuity. Pearson correlation coefficients were calculated across voxels between the two modalities in grey and white matter of each subject respectively and between normalized mean values of ASL and CT perfusion measures in major vascular territories. RESULTS: Significant associations between ASL and CT perfusion were detected using subjective ratings, voxel-wise analysis in grey and white matter and region of interest (ROI)-based analysis of normalized mean perfusion. The correlation between ASL CBF and CT perfusion was improved using the multi-delay pCASL protocol compared to CBF acquired at a single PLD of 2 s (P < 0.05). CONCLUSIONS: There is a correlation between perfusion data from ASL and CT perfusion imaging in patients with moyamoya disease. Multi-delay ASL can improve CBF quantification, which could be a prognostic imaging biomarker in patients with moyamoya disease. KEY POINTS: • Simultaneous measurements of CBF and ATT can be achieved using multi-delay pCASL. • Multi-delay ASL was compared with CT perfusion in patients with moyamoya disease. • Statistical analyses showed significant associations between multi-delay ASL and CT perfusion. • Multi-delay ASL can improve CBF quantification in moyamoya disease.

Neuroimaging of white matter injury, intraventricular and cerebellar hemorrhage.

White matter injury and hemorrhage are common findings in extremely preterm infants. Large hemorrhages and extensive cystic lesions are identified with cranial ultrasound. MRI, which is more sensitive, is especially useful in the identification of small intraventricular hemorrhage; cerebellar hemorrhage; punctate lesion in the white matter and cerebellum; and diffuse, noncystic white matter injury. Imaging sequences such as diffusion-weighted, diffusion tensor, and susceptibility weighted imaging may improve recognition and prediction of outcome. These techniques improve understanding of the underlying pathophysiology of white matter injury and its effects on brain development and neurodevelopmental outcome.

The role of neuroimaging in predicting neurodevelopmental outcomes of preterm neonates.

Magnetic resonance imaging (MRI) is a safe and high-resolution neuroimaging modality that is increasingly used in the neonatal population to assess brain injury and its consequences on brain development. It is superior to cranial ultrasound for the definition of patterns of both white and gray matter maturation and injury and therefore has the potential to provide prognostic information on the neurodevelopmental outcomes of the preterm population. Furthermore, the development of sophisticated MRI strategies, including diffusion tensor imaging, resting state functional connectivity, and magnetic resonance spectroscopy, may increase the prognostic value, helping to guide parental counseling and allocate early intervention services.

Different locations but common associations in subcortical hypodensities of presumed vascular origin: cross-sectional study on clinical and neurosonologic correlates.

BACKGROUND: Subcortical hypodensities of presumed vascular etiology (SHPVO) are a clinical, radiological and neuropathological syndrome with a still largely unexplained pathophysiology. Parallel to the clinical heterogeneity, there is also recognised cerebral topographical diversity with undetermined etiological implications. Our aim is to assess clinical and neurosonological predictors of SHPVO according to their location. METHODS: Cross sectional analysis of consecutive patients that underwent neurosonologic evaluation and head CT within one month, during a one year period. We excluded patients with absent temporal sonographic window, any pathology with a possible confounding effect on cerebral arterial pulsatility, atrial fibrillation and other etiologies of white matter diseases. The mean pulsatility index (PI) of both middle cerebral arteries was measured in the middle third of the M1 segment; intima media thickness was evaluated in the far wall of both common carotid arteries. SHPVO were rated by analysis of head CT in deep white matter (DWMH), periventricular white matter (PVWMH) and basal ganglia (BGH). We conducted a multivariate ordinal logistic regression model including all clinical, demographic and ultrasonographic characteristics to determine independent associations with SHPVO. RESULTS: We included 439 patients, mean age 63.47 (SD: 14.94) years, 294 (67.0%) male. The independent predictors of SHPVO were age (OR = 1.067, 95% CI: 1.047-1.088, p < 0.001 for DWMH; OR = 1.068, 95% CI: 1.049-1.088, p < 0.001 for PVWMH; OR = 1.05, 95% CI: 1.03-1.071, p < 0.001 for BGH), hypertension (OR = 1.909, 95% CI: 1.222-2.981, p = 0.004 for DWMH; OR = 1.907, 95% CI: 1.238-2.938, p = 0.003 for PVWMH; OR = 1.775, 95% CI: 1.109-2.843, p = 0.017 for BGH) and PI (OR = 17.994, 95% CI: 6.875-47.1, p < 0.001 for DWMH; OR = 5.739, 95%CI: 2.288-14.397, p < 0.001 for PVWMH; OR = 11.844, 95% CI: 4.486-31.268, p < 0.001 for BGH) for all locations of SHPVO. CONCLUSIONS: Age, hypertension and intracranial pulsatility are the main independent predictors of SHPVO across different topographic involvement and irrespective of extracranial atherosclerotic involvement.

Evaluation of cerebrovascular reserve using xenon-enhanced CT scanning in patients with symptomatic middle cerebral artery stenosis.

Cerebrovascular reserve (CVR) is an important prognostic factor in patients with major cerebral arterial steno-occlusive disease. However, few studies have examined CVR in symptomatic intracranial stenosis without ipsilateral extracranial internal carotid artery stenosis. This study sought to evaluate CVR in patients with symptomatic middle cerebral artery (MCA) stenosis using xenon-enhanced computed tomography (Xe/CT) with acetazolamide (ACZ) challenge. Twelve patients with symptomatic MCA stenosis were recruited. All patients were examined by Xe/CT to quantitatively measure resting cerebral blood flow (CBF) and received ACZ challenge to evaluate CVR. For resting CBF, no significant differences were found between the sides in four regions of interest. After the ACZ challenge test, the CVR was significantly different between hemispheres (ipsilateral versus contralateral CVR: 12.9 ± 24.3% versus 28.0 ± 16.8%, respectively; p=0.005) and in the MCA territory (ipsilateral versus contralateral CVR: 8.7 ± 24.7% versus 29.3 ± 24%, respectively; p=0.003). However, no significant differences in CVR were detected between cortical comparisons and white matter comparisons from the two sides. Thus, ACZ-challenge Xe/CT is useful for the measurement of CBF and CVR in these patients. Impaired CVR is an important characteristic of patients with symptomatic MCA stenosis.

Clinical use of (11)C-methionine and (18)F-FDG-PET for germinoma in central nervous system.

OBJECTIVE: The purpose of this study was to examine the (11)C-methionine (MET) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) findings of central nervous system (CNS) germinoma and the diagnostic utility of these findings. METHODS: We retrospectively evaluated the cases of 10 patients who were diagnosed with CNS germinoma according to their histopathological or clinical findings. All the patients underwent pretreatment MET and/or FDG-PET scans, and the resultant images were assessed qualitatively and quantitatively. In the qualitative assessments, we used 3- and 5-grade visual scoring systems for the MET- and FDG-PET images, respectively. In the quantitative assessments, the maximal standardized uptake value (SUVmax) and the ratio of the SUVmax of the tumor (T) divided by the mean SUV for the normal white or gray matter [T/N (WM), T/N (GM)], was calculated. RESULTS: The mean and SD values of SUVmax, T/N (WM), and T/N (GM) were 1.9 ± 1.4, 2.5 ± 1.3, and 1.7 ± 0.9 on MET-PET and 5.8 ± 2.2, 1.6 ± 0.5, and 0.8 ± 0.2 on FDG-PET, respectively. On MET-PET, only one lesion was not detected. On the other hand, on FDG-PET all of the lesions exhibited uptake values that were intermediate between those of the normal white matter and gray matter. CONCLUSION: In terms of its tumor-contouring ability, MET is a good tracer for diagnosing CNS germinomas; therefore, MET-PET is considered to be useful for planning biopsies or surgery. Although FDG-PET is capable of detecting CNS germinomas, it produced insufficient image contrast in the present study. Further studies are needed before FDG-PET can be used in clinical examinations of CNS germinoma.

Bootstrap methods for estimating PET image noise: experimental validation and an application to evaluation of image reconstruction algorithms.

OBJECTIVE: Accurate and validated methods for estimating regional PET image noise are helpful for optimizing image processing. The bootstrap is a data-based simulation method for statistical inference, which can be used to estimate the PET image noise without repeated measurements. The aim of this study was to experimentally validate bootstrap-based methods as a tool for estimating PET image noise and demonstrate its usefulness for evaluating image reconstruction algorithms. METHODS: Two bootstrap-based method, the list-mode data bootstrap (LMBS) and the sinogram bootstrap (SNBS), were implemented on a clinical PET scanner. A uniform cylindrical phantom filled with (18)F solution was scanned using list-mode acquisition. A reference standard deviation (SD) map was calculated from 60 statistically independent measured list-mode data. Using one of the 60 list-mode data, 60 bootstrap replicates were generated and used to calculate bootstrap SD maps. Brain (18)F-FDG data from a healthy volunteer were also processed as an example of the bootstrap application. Three reconstruction algorithms, FBP 2D and both 2D and 3D versions of dynamic row-action maximum likelihood algorithm (DRAMA), were assessed. RESULTS: For all the reconstruction algorithms used, the bootstrap SD maps agreed well with the reference SD map, confirming the validity of the bootstrap methods for assessing image noise. The two bootstrap methods were equivalent with respect to the performance of image noise estimation. The bootstrap analysis of the FDG data showed the better contrast-noise relation curve for DRAMA 3D compared to DRAMA 2D and FBP 2D. CONCLUSIONS: The bootstrap methods provide the estimates of image noise for various reconstruction algorithms with reasonable accuracy, require only a single measurement, not repeated measures, and are, therefore, applicable for a human PET study.

Effects of local corticosteroid injection on electrical properties of aß-fibers in carpal tunnel syndrome.

Very few data are available on the structural and functional effects of corticosteroids on peripheral nerve fibers. This paper is addressed to verify possible changes in the functional properties of myelinated Aß fibers of the median nerve in carpal tunnel syndrome (CTS) after a local injection of triamcinolone acetate. Thirteen subjects affected by mild CTS and 13 controls were selected. Clinical, electrophysiological, and ultrasonographic (cross sectional area: CSA) data of the median nerve were quantified at 0 (pre-injection), and 1 month after triamcinolone injection at wrist. We analyzed the input-output curves constructed by plotting the response amplitude as a function of stimulus intensity. After corticosteroid injection, all patients experienced symptom relief, the median nerve CSA decreased, and the plateau value of the input-output curve was significant higher than before the treatment. Pre injection, we observed a significant inverse correlation between median nerve CSA and plateau value of the input-output curve, which remained significant even after the corticosteroid injection. The Aß fibers with higher electrical threshold undergo conduction recovery after local corticosteroid injection. In CTS, combined mechanisms might contribute to resolution of symptoms: anti-edema/anti-inflammatory action and direct effect on the electrical properties of the nerve fibers.

Semi-automated 3D segmentation of major tracts in the rat brain: comparing DTI with standard histological methods.

Researchers working with rodent models of neurological disease often require an accurate map of the anatomical organization of the white matter of the rodent brain. With the increasing popularity of small animal MRI techniques, including diffusion tensor imaging (DTI), there is considerable interest in rapid segmentation methods of neurological structures for quantitative comparisons. DTI-derived tractography allows simple and rapid segmentation of major white matter tracts, but the anatomic accuracy of these computer-generated fibers is open to question and has not been rigorously evaluated in the rat brain. In this study, we examine the anatomic accuracy of tractography-based segmentation in the adult rat brain. We analysed 12 major white matter pathways using semi-automated tractography-based segmentation alongside manual segmentation of Gallyas silver-stained histology sections. We applied four fiber-tracking algorithms to the DTI data-two integration methods and two deflection methods. In many cases, tractography-based segmentation closely matched histology-based segmentation; however different tractography algorithms produced dramatically different results. Results suggest that certain white matter pathways are more amenable to tractography-based segmentation than others. We believe that these data will help researchers decide whether it is appropriate to use tractography-based segmentation of white matter structures for quantitative DTI-based analysis of neurologic disease models.

Association of extensive myelinated nerve fibers and high degree myopia: case report.

Unilateral extensive myelination of the peripapillary nerve fibers may be associated with anisometropic myopia, strabismus, and reduced vision. Myelination of optic nerve fibers terminate at lamina cribrosa. Yet in some patients, myelination progresses into the peripapillary retinal nerve fibers and may affect the visual acuity. In this report, we described 4 patients. All patients presented extensive peripapillary myelinated nerve fibers associated with myopic anisometropia. After routine ophthalmic and orthoptic examinations, all patients underwent treatment for amblyopia through correction with spectacles, contact lenses, and the occlusion of the good eye. Corrected visual acuity improved in 1 patient, but 3 patients had no increase in visual acuity despite treatment with full cycloplegic refraction and appropriate patching. Probably because of structural abnormalies of the macula, visual results are often disappointing with appropriate correction of the refractive error and occlusion.

Cognitive aging in persons with minimal amyloid-ß and white matter hyperintensities.

Substantial individual differences exist in the magnitude of the cognitive decline associated with normal aging. Potential contributors to this intersubject variability include white matter hyperintensities (WMH) and preclinical Alzheimer's disease, evident as increased brain amyloid. This study examined whether older individuals with minimal evidence of WMH and/or brain amyloid-beta (seen on positron emission tomography with the Pittsburgh compound B radiotracer-PiB) still showed significant cognitive decrements compared to the young. Older individuals, conservatively screened for normal range performance on an extensive neuropsychological battery, underwent structural magnetic resonance imaging (MRI) and PiB scans and performed tests of information processing speed, working memory and inhibitory function. The elderly were divided into PiB(+) and PiB(-) groups based on radiotracer retention. There were no significant differences in cognitive performance between PiB(+) and PiB(-) elderly. However, both PiB groups performed significantly worse than did the young on cognitive testing. WMH burden in the same individuals was quantified by consensus ratings using a 10 point scale with a median split defining two groups, WMH(+) and WMH(-). There were no differences in cognitive performance between WMH(+) and WMH(-) individuals, but both WMH groups performed significantly worse than did the young. Older participants who were both PiB(-) and WMH(-) also performed significantly worse than did the young in all three cognitive domains. The present results suggest that normal-elderly individuals whose brain scans show minimal evidence of amyloid deposition or WMH, still demonstrate a major decrement in comparison to younger persons on measures of processing resources and inhibitory efficiency.

Accuracy of transcranial ultrasound in the detection of mild white matter lesions in newborns.

Cranial Ultrasound (cUS) may not be sensitive enough to detect subtle white matter (WM) injuries. Our study compared serial cUS with MRI at term equivalent age (TEA) to determine if it is possible to identify an ultrasound representation of subtle diffuse WM injuries such as punctate lesions (PWMLs) and diffuse excessive high signal intensity (DEHSI). Fifty-six very preterm infants were scanned sequentially from birth to TEA, an MRI was performed at TEA. Each echodensity found on cUS was classified as absent, transient (≤7 days), or prolonged (>7 days). A transient periventricular echodensity was detected in seven infants (12.5%), and a prolonged echodensity in 15 (26.8%). MRI examinations were performed in all 56 infants. No altered signal intensity was found in 18 infants (32.1%). DEHSI was detected in 14 infants (25%), and PWMLs were detected in eight babies (14.3%). Both abnormalities were found in 16 infants (28.6%). The positive predictive values of the prolonged echodensity for DEHSI and PWMLs were 86.7% and 46.7% respectively. However, a significant statistical correspondence (p=0.002, Odds Ratio 11.9) was found comparing DEHSI with cUS abnormal echodensities. Serial cUS during the neonatal period in preterm infants is essential and cannot be replaced with MRI at TEA. MRI seems to be more reliable in detecting mild or moderate WM abnormalities. However, serial cUS performed by an experienced neonatologist can provide valuable information on early WM changes such as prolonged echodensities that could potentially lead to a diffuse injury.

Alterations in white matter microstructure in women recovered from anorexia nervosa.

OBJECTIVE: A recent study of ill individuals with anorexia nervosa (AN) reported microstructural alterations in white matter integrity including lower fractional anisotropy and higher mean diffusivity. This study was designed to determine whether such alterations exist in long-term recovered AN individuals and to examine potential associations with underlying AN traits. METHOD: Twelve adult women recovered from restricting-type AN and 10 control women were studied using diffusion tensor imaging. RESULTS: Overall, there was no significant fractional anisotropy alteration in recovered AN, in contrast to a prior study reporting lower fractional anisotropy in ill AN. Further, recovered AN showed lower mean diffusivity in frontal, parietal and cingulum white matter relative to control women, contrary to elevated mean diffusivity previously reported in ill AN. Lower longitudinal diffusivity in recovered AN was associated with higher harm avoidance. However, more severe illness history was associated with worse white matter integrity after recovery in the same direction as reported in prior work. DISCUSSION: Our findings suggest that fractional anisotropy in recovered AN is not different from controls, however, a novel pattern of lower mean diffusivity was evidenced in recovered AN, and this alteration was associated with harm avoidance. Notably, severity of illness history may have long-term consequences, emphasizing the importance of aggressive treatment.

Early CT signs of hypoxia in patients with subarachnoid hemorrhage presenting with cardiac arrest: early CT signs in SAH patients presenting with CA.

BACKGROUND: For cardiac arrest (CA) victims, brain computed tomography (CT) may serve as a prognosticator. Loss of gray-white matter discrimination (GWMD) and sulcal edema/effacement are reliable CT signs of hypoxia, and a time window may exist for development of these signs. Most data are derived from CA victims of cardiac etiology, however, and CT signs have rarely been evaluated in victims of CA secondary to subarachnoid hemorrhage (SAH). METHODS: A retrospective study was conducted to clarify the incidence, temporal profile, and prognostic significance of early CT signs in resuscitated SAH-CA patients. RESULTS: During a 6-year period, 35 SAH-CA patients were identified. CT signs were observed in 94 %: loss of GWMD was observed in 94 %, whereas sulcal edema/effacement was observed in 77 %. In 29 patients, the interval between CA and the return of spontaneous circulation (ROSC) was estimated. CT signs developed almost invariably when the CA-ROSC interval exceeded 10 min. Loss of GWMD always preceded sulcal edema/effacement. None of the 35 patients achieved long-term survival, regardless of the presence of the CT signs. CONCLUSION: CT signs may develop earlier in patients with SAH-CA than CA of cardiac origin. Because of a poor prognosis, early CT signs are not useful prognosticators in that population.

Genetically proven cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in a 3-year-old.

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) has always been considered to be a middle-age-onset disease. Diagnosis is confirmed by genetic testing and the finding of the Notch3 mutation or by skin biopsy. Imaging plays a pivotal and crucial role in confirming this diagnosis by identifying white matter changes early in the disease. This can be useful in screening symptomatic patients with a family history of the disease. CADASIL cases have been reported recently in children. We report our experience with CADASIL in a 3-year-old boy.

Assessing prenatal white matter connectivity in commissural agenesis.

Complete or partial agenesis of the corpus callosum are rather common developmental abnormalities, resulting in a wide spectrum of clinical neurodevelopmental deficits. Currently, a significant number of these cases are detected by prenatal sonography during second trimester screening examinations. However, major uncertainties about a detailed morphological diagnosis and the clinical significance do not allow accurate prenatal counselling. Here, we were able to demonstrate the 3D connectivity of aberrant commissural tracts in 16 cases with complete and four cases with partial callosal agenesis using the foetal magnetic resonance imaging techniques of diffusion tensor imaging and tractography in utero and in vivo between gestational weeks 20 and 37. The 'misguided' pre-myelinated callosal axons that represent the bundle of Probst were non-invasively visualized, and they showed a degree of structural integrity similar to that of the callosal pathways of age-matched foetuses without cerebral pathologies. In two foetuses, we were able to prove, by post-mortem histology, that diffusion tensor imaging allows the depiction of the bundle of Probst, even during early stages of pre-myelination at 20 and 22 gestational weeks. In cases with partial callosal agenesis, an aberrant sigmoid-shaped bundle was prenatally depicted, confirming the findings of heterotopic interhemispheric connectivity in adults with partial callosal agenesis. In addition to the corpus callosum, other white matter pathways were also involved, including somatosensory and motor pathways that showed significantly higher fractional anisotropy values in cases with callosal agenesis compared with control subjects. A detailed prenatal assessment of abnormal white matter connectivity in cases of midline anomalies will help to explain and understand the clinical heterogeneity in these cases, taking future foetal neurological counselling strategies to a new level.