Congenital Cytomegalovirus Infection Following Second and Third Trimester Maternal Infection Is Associated With Mild Childhood Adverse Outcome Not Predicted by Prenatal Imaging.

BACKGROUND: While it is clear that first trimester congenital cytomegalovirus (CMV) infection can lead to serious neonatal and childhood adverse outcome, the extent of the effect of second and third trimester congenital CMV infection is still unclear. Our aim was to study the short- and long-term outcomes following second and third trimester infection and to evaluate the contribution of prenatal imaging in a prospective cohort. METHODS: We studied pregnant women with primary CMV infection in the second and third trimesters, as diagnosed by well-dated seroconversion, and proof of vertical CMV transmission. All patients underwent serial prenatal ultrasound (US) and most of them fetal magnetic resonance imaging (MRI). Follow-up information was obtained from hospital charts and by telephone interviews with parents. RESULTS: Primary CMV infection occurred in 135 patients, 107 and 28 with second and third trimester infection, respectively. The incidence proportion of composite outcome (hearing loss or neurodevelopmental impairment) following second trimester infection was 7% (7/100, after excluding cases that were terminated) with a 3% incidence of partial unilateral sensory neural hearing loss and a 5% incidence of minor neurodevelopmental abnormalities, including slight verbal and motor delay. Following third trimester infection, there was one case of a very mild motor delay. The incidence proportion of abnormal prenatal findings on US or MRI was not significantly correlated to hearing loss or neurodevelopmental abnormalities. CONCLUSIONS: Second trimester infection is associated with a slight risk of developing mild childhood sequelae, mostly partial unilateral hearing loss, which may develop late in childhood. Prenatal imaging failed to predict the development of childhood adverse outcome.

What does the normal fetal face look like? MR imaging of the developing mandible and nasal cavity.

PURPOSE: Analyze fetal facial structures using MR imaging scans in an aim to establish normal biometrical measures of fetal nasal and mandibular structures for multiple gestational weeks, comprise nomograms and compare female and male fetuses. METHODS: A Historic cohort study of 255 fetal facial MR imaging scans was performed at a tertiary medical center during a 4-year period. Clinical data was collected from electronic medical charts. Length of septal height (SH), septal length (SL), Interocular Distance(IOD), maximal nasal length(MNL), mandibular vertebral length(MVL), antero-posterior diameter(APD), inferior facial angle(IFA) and biparietal diameter(BPD) were measured and compared with gender and gestational age (GA). Interrater and intrarater reliability was investigated. RESULTS: Normal measures were established for each gestational age. We found that all parameters but IFA correlated with GA. Males had a longer SL, BPD and MNL while females had a wider IFA. CONCLUSIONS: Novel facial biometric parameters that correlate with GA hold cardinal information for the prenatal evaluation of facial development and thus surface the need for additional research in order to asses these findings as radiologic markers for facial structural pathologies.

Assessment of the Association Between Congenital Heart Defects and Brain Injury in Fetuses through Magnetic Resonance Imaging.

BACKGROUND: Congenital heart defects (CHD) may be associated with neurodevelopmental abnormalities mainly due to brain hypoperfusion. This defect is attributed to the major cardiac operations these children underwent, but also to hemodynamic instability during fetal life. Advances in imaging techniques have identified changes in brain magnetic resonance imaging (MRI)in children with CHD. OBJECTIVES: To examine the correlation between CHD and brain injury using fetal brain MRI. METHODS: We evaluated 46 fetuses diagnosed with CHD who underwent brain MRI. CHD was classified according to in situs anomalies, 4 chamber view (4CV), outflow tracts, arches, and veins as well as cyanotic or complex CHD. We compared MRI results of different classes of CHD and CHD fetuses to a control group of 113 healthy brain MRI examinations. RESULTS: No significant differences were found in brain pathologies among different classifications of CHD. The anteroposterior percentile of the vermis was significantly smaller in fetuses with abnormal 4CV. A significantly higher biparietal diameter was found in fetuses with abnormal arches. A significantly smaller transcerebellar diameter was found in fetuses with abnormal veins. Compared to the control group, significant differences were found in overall brain pathology in cortex abnormalities and in extra axial findings in the study group. Significantly higher rates of overall brain pathologies, ventricle pathologies, cortex pathologies, and biometrical parameters were found in the cyanotic group compared to the complex group and to the control group. CONCLUSIONS: Fetuses with CHD demonstrate findings in brain MRI that suggest an in utero pathogenesis of the neurological and cognitive anomalies found during child development.

Neurodevelopmental outcome following prenatal diagnosis of a short corpus callosum.

OBJECTIVE: Data regarding the neurodevelopmental outcome of fetal short corpus callosum (CC) diagnosed according to standard reference charts is scarce. The purpose of this study was to assess whether the finding is related to neurodevelopmental delay, and to examine reclassification to normal fetal CC length using CC length/EFW ratio. METHOD: Historical prospective cohort study including pregnant women who were referred for fetal neurosonogram due to abnormal CC. Short CC was defined below the 5th percentile according to reference charts. Twenty cases were included in the study group and compared with a control group of 59 normal cases. The patients in the study group were divided into two groups according to CC length/EFW ratio. Children's neurodevelopment was assessed using the Vineland Adaptive Behavior Scale (VABS). RESULTS: VABS scores were within normal range in 90% of the cases. There was no significant statistical difference between the study group and the control group. In addition, there was no statistically significant difference between fetuses reclassified as normal callosal length according to CC length/EFW ratio in comparison to the control group. CONCLUSION: The neurodevelopmental outcome of fetuses with diagnosed short CC did not differ from the neurodevelopment of normal fetuses in the control group.

Prenatal diagnosis of arachnoid cysts: MRI features and neurodevelopmental outcome.

OBJECTIVE: Arachnoid cysts (AC) are congenital lesions comprising 1% of all intracranial mass lesions. The aim of this study was to characterize arachnoid cysts and their neurodevelopmental outcome and to compare it with the outcome of children without AC. METHODS: This is a retrospective cohort study of arachnoid cysts detected prenatally by fetal MRI in 29 fetuses compared to a control group of 59 fetuses without arachnoid cyst who were examined by MRI. The cohort was investigated from two different angles: anatomical and developmental. Anatomical analyzation, the cohort was divided into 2 groups by the arachnoid cyst anatomical location: group A (n = 9), which included cases with supratentorial cyst, and group B (n = 20), which included cases with infratentorial cyst. Developmental analyzation, the cohort was divided into 2 groups by the neurodevelopmental outcome: group γ (n = 5) which included cases that were affected by arachnoid cyst presence, and group δ (n = 17) which included cases that had neurodevelopmental outcome within the normal range. Data collected included prenatal history, MRI features, sonographic follow up, and neurodevelopmental outcome. RESULTS: In 22/29 cases we achieved a long-term follow up, by evaluation of children development in a range of ages from 6 months to 6 years. In group A (n = 9), 4 infants had normal outcome, 2 had abnormal outcome, 1 pregnancy was terminated, and 2 cases were not cooperative with the study. In group B (n = 20), 13 infants had normal outcome, 3 had abnormal outcome, and 4 cases were not cooperative with the study. CONCLUSIONS: From all cases with AC detected by fetal MRI, 77.3% had normal neurodevelopmental outcome and 22.7% had abnormal neurodevelopment.

Cervical MRI Rating Scale: Innovative Approach to Differentiate between Demyelinating and Disc Lesions.

PURPOSE: The difficult differentiation between multiple sclerosis (MS) lesions and cervical spondylotic myelopathy (CSM) in the cervical spine is well known. The magnetic resonance imaging (MRI) appearance of both lesions is similar, and clinical parameters are usually used for diagnosis. The objective was to establish a reliable radiologic paradigm for diagnosis of demyelinating lesions in the cervical spine. METHODS: The MRI studies of 33 patients with MS (42 lesions) and 55 patients with CSM (60 lesions) were obtained. Lesions were evaluated for vertebral level, lesion location and size in the sagittal and axial planes, cord thickness, well-defined or ill-defined borders, presence of edema and enhancement with gadolinium. Significant differences were used to create a paradigm, which was used for the evaluation of a different group of 32 MRIs with 42 concomitant MS and CSM lesions. RESULTS: Significant differences were seen in the level, location within the cord in both planes, lesion size, cord thickness and lesion border. The MS lesions were well-defined lesions found in C1-3, posterior in the sagittal plane, central in the axial plane, with a normal or increased cord thickness. Good agreement was seen in the validation stage. CONCLUSION: The new CSM-MS lesion score allows accurate diagnosis of demyelinating lesions in the cervical spine vs. CSM lesions.

Neonatal Cervical Osteomyelitis With Bilateral Upper Limb Paresis.

Neonatal cervical osteomyelitis is extremely rare, with only a few cases having been reported. We report a neonate with cervical osteomyelitis and extensive inflammation of the surrounded tissues that caused nerve root compression and upper limb paresis.

Nocardiosis: a 15-year experience in a tertiary medical center in Israel.

OBJECTIVES: The objective of this study is to characterize the common risk factors, clinical presentation, imaging findings, treatment and outcome of nocardial infection. DESIGN AND SETTINGS: A retrospective cohort study. We reviewed the charts of all patients with nocardiosis in the Chaim Sheba Medical Center, a tertiary medical center in Israel, between the years 1996 and 2011. RESULTS: A total of 39 patients who had positive culture of Nocardia were analyzed. The majority of our patients were immunocompromised (74.5%), mostly due to corticosteroid therapy. None had HIV/AIDS. The clinical presentation was either acute or a chronic smoldering illness. The three major clinical syndromes were pleuropulmonary, neurological and skin/soft tissue infection about 20.5% each. Pathology in the lungs was seen in most of the patients by CT scan; discrete nodules and wedge shaped pleural based consolidations were the most frequent findings. Brain lesions consistent with abscesses were detected in 10 patients by brain imaging. Some cases had relapsing disease in spite of antimicrobial treatment. 25% of examined isolates were resistant to trimethoprim/sulfamethoxazole. The duration of intravenous antimicrobial treatment ranged from one month to over a year in the severe cases. One year mortality rate was 32%. CONCLUSION: Nocardiosis requires a high clinical index of suspicion in order to diagnose and treat promptly. Disease extent and bacterial susceptibility have important implications for prognosis and treatment.

The EEG in E200K familial CJD: relation to MRI patterns.

The aim of the study was to examine the relationship between EEG abnormalities and the pattern of MRI changes in familial Creutzfeldt-Jakob Disease (fCJD) patients with E200K mutation. As part of a controlled, prospective study, 13 E200K fCJD patients underwent comprehensive evaluations, with EEG and an extensive MRI protocol that included one of the most prion-disease sensitive sequences, diffusion-weighted imaging (DWI). The relationship between EEG abnormalities and the pattern of DWI hyperintensities was examined. EEG demonstrated the classical CJD finding of PSWC (periodic sharp wave complexes) in five patients (38%) while in eight patients (62%) the EEG showed only slow activity. Six patients showed the typical cortical changes on MRI, and in five of them (83%) concordance between the MRI and the EEG was found. Five patients had isolated basal ganglia involvement per MRI, and in two of them (40%) concordance between the MRI and the EEG laterality was found. In the remaining two patients MRI did not show any changes suggesting CJD and EEG showed focal slow activity. The EEG of our E200K fCJD patients appears similar to that of the largest prion disease patient group, sporadic CJD (sCJD). EEG abnormalities in E200K fCJD appear to correlate mainly with cortical pathology, as revealed by DWI, rather than basal ganglia pathology. The observation that PSWC abnormalities reflect cortical rather than basal ganglia pathology is significant with respect to theories of the origins of EEG abnormalities in prion disease.

Pruritus in familial Creutzfeldt-Jakob disease: a common symptom associated with central nervous system pathology.

Pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with Creutzfeldt-Jakob disease (CJD), and its anatomical background is not well defined. The present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in CJD patients and investigate its anatomical substrate by MRI. The study group included consecutive familial and sporadic CJD patients carrying the E200K PRNP mutation followed up in a longitudinal prospective study between the years 2005 and 2008. Pruritus was prospectively screened for and diffusion-weighted imaging (DWI) was used to correlate brain diffusion abnormalities with pruritus in CJD patients. Pruritus was present in 6/31 (19.35%) patients with familial disease (fCJD) and in none of the patients with sporadic disease (sCJD). Pruritus was a presenting symptom in one patient and evolved during the course of the disease in the other five patients. The pruritus was generalized in three patients, regional in two and localized in one patient. It was transient in one patient and continued throughout the disease in five patients. DWI showed that pruritus was significantly associated with reduced diffusion in the several areas known to be affected by CJD, but most significantly in the midbrain periaqueductal grey matter. Pruritus is relatively common in patients with familial CJD carrying the E200K mutation. Our findings point to a central origin that involves damage to the inhibitory gating mechanism for itch in the periaqueductal grey matter.

Computed tomographic analysis of calvarial hyperostosis in captive lions.

Osseous malformations in the skull and cervical vertebrae of lions in captivity are believed to be caused by hypovitaminosis A. These often lead to severe neurologic abnormalities and may result in death. We describe the characterization of these abnormalities based on computed tomography (CT). CT images of two affected and three healthy lions were compared with define the normal anatomy of the skull and cervical vertebrae and provide information regarding the aforementioned osseous malformations. Because bone structure is influenced by various factors other than the aforementioned disease, all values were divided by the skull width that was not affected. The calculated ratios were compared and the most pronounced abnormalities in the affected lions were, narrowing of the foramen magnum, thickening of the tentorium osseus cerebelli and thickening of the dorsal arch of the atlas. CT is useful for detection of the calvarial abnormalities in lions and may be useful in further defining this syndrome.

The application of MRI for depiction of subtle blood brain barrier disruption in stroke.

The development of imaging methodologies for detecting blood-brain-barrier (BBB) disruption may help predict stroke patient's propensity to develop hemorrhagic complications following reperfusion. We have developed a delayed contrast extravasation MRI-based methodology enabling real-time depiction of subtle BBB abnormalities in humans with high sensitivity to BBB disruption and high spatial resolution. The increased sensitivity to subtle BBB disruption is obtained by acquiring T1-weighted MRI at relatively long delays (~15 minutes) after contrast injection and subtracting from them images acquired immediately after contrast administration. In addition, the relatively long delays allow for acquisition of high resolution images resulting in high resolution BBB disruption maps. The sensitivity is further increased by image preprocessing with corrections for intensity variations and with whole body (rigid+elastic) registration. Since only two separate time points are required, the time between the two acquisitions can be used for acquiring routine clinical data, keeping the total imaging time to a minimum. A proof of concept study was performed in 34 patients with ischemic stroke and 2 patients with brain metastases undergoing high resolution T1-weighted MRI acquired at 3 time points after contrast injection. The MR images were pre-processed and subtracted to produce BBB disruption maps. BBB maps of patients with brain metastases and ischemic stroke presented different patterns of BBB opening. The significant advantage of the long extravasation time was demonstrated by a dynamic-contrast-enhancement study performed continuously for 18 min. The high sensitivity of our methodology enabled depiction of clear BBB disruption in 27% of the stroke patients who did not have abnormalities on conventional contrast-enhanced MRI. In 36% of the patients, who had abnormalities detectable by conventional MRI, the BBB disruption volumes were significantly larger in the maps than in conventional MRI. These results demonstrate the advantages of delayed contrast extravasation in increasing the sensitivity to subtle BBB disruption in ischemic stroke patients. The calculated disruption maps provide clear depiction of significant volumes of BBB disruption unattainable by conventional contrast-enhanced MRI.

Parry-Romberg syndrome presenting as status migrainosus.

Parry-Romberg is a rare syndrome of unknown origin, characterized by hemiatrophy of the face including subcutaneous tissue, skeletal muscle, and bones, along with various ocular and central nervous system abnormalities. Some investigators consider that injury to the sympathetic fibers of the trigeminal nerve is a cause for evolution of this syndrome. Various central nervous system symptoms have been reported in correlation with the syndrome, including epilepsy and hemiparesis. These symptoms were related to ipsilateral (or, less frequently, contralateral) facial lesions, and in a few case reports were consistent with Rasmussen's encephalitis-like lesions. Many clinical features overlap between facial linear scleroderma and en coup de sabre syndrome, which is characterized by localized inflammation leading to atrophy of the skin and subcutaneous tissues mainly on one side of the face; such overlap can lead to confusion in diagnosis. Furthermore, central nervous system involvement has been reported in en coup de sabre syndrome, leading to further misdiagnosis. The distinction between these two disorders is much disputed. Detailed here is the case of a child who had been diagnosed with en coup de sabre syndrome presenting with severe status migrainosus. Subsequent pathologic clinical, and neuroimaging findings led to a diagnosis of Parry-Romberg syndrome. This diagnosis is set in the context of the similarities, contradictions, and growing confusion between the two syndromes.

Multiple congenital skull fractures as a presentation of Ehlers-Danlos syndrome type VIIC.

We describe a newborn infant with multiple congenital skull fractures and intracranial hemorrhage. He also had multiple skin folds suggesting a connective tissue abnormality. Electron microscopy of the skin biopsy showed collagen abnormalities with a "hieroglyphic appearance." The analysis of the synthesis of collagen in the cultured dermal fibroblasts demonstrated an accumulation of procollagen I. Molecular analysis found a nonsense mutation Q225X in ADAMTS2 gene, which encodes procollagen I N-terminal proteinase. All these findings confirmed the diagnosis of Ehlers-Danlos syndrome type VIIC (MIM 225410). Family studies suggested a founder effect in Ashkenazi Jews originating from Belarus. Prenatal diagnosis in the subsequent pregnancy reassured the parents that the fetus was an unaffected carrier.

Quantitative MRI measurements of human fetal brain development in utero.

Magnetic resonance imaging (MRI) allows for high resolution imaging of the central nervous system. We have tested the feasibility of using MRI in conjunction with quantitative image analysis to perform volumetric measurements of the brain in the developing human fetus in utero. The database comprises MR images of a total of 56 fetuses (gestational age 25-41 weeks) referred because of suspected abnormalities due to ultrasound findings, family history or maternal illness and scanned on a 1.5 T MR system using a single-shot fast spin echo (SSFSE) T2 sequence, slice thickness 3 mm, no gap. Four out of the 56 scans could not be used in the analysis due to poor image quality. Automatic segmentation (using NIH Image routines) was found to be unreliable in these fetal brains, so cerebral, cerebellar and ventricular regions were traced manually. Ventricular volumes did not vary with gestational age in normal fetuses (N=27, R=0.05, p=0.8) while cerebral parenchyma and cerebellum volumes increased significantly during the same period (R=0.67, p=0.0002 and R=0.51, p=0.0066 respectively). Two calculated parameters: percent ventricular asymmetry and volume ratio of ventricles to hemispheric parenchyma were found to be very sensitive to ventricular pathology; such that the mean value of the latter in normal fetuses was 4.4%+/-0.56 (mean+/-SEM, N=27) compared to 34.3%+/-17.6 (N=6, p<0.0001) in fetuses with ventriculomegaly. These results support the use of image analysis and MRI to produce normal growth curves as well as quantitative severity assessments of brain pathologies in the developing human fetus.

Low-dose recombinant human thyrotropin-aided radioiodine treatment of large, multinodular goiters in elderly patients.

OBJECTIVE: We aimed to assess low-dose recombinant human thyroid-stimulating hormone (rhTSH)-aided, fixed-activity radioiodine therapy of large, multinodular goiters (MNGs) in elderly patients with comorbidities. DESIGN: This was a short-term, observational study. METHODS: We measured 24-h thyroid radioiodine uptake (RAIU) of 2 microCi 131-iodine at baseline and 24 h after intramuscular injection of 0.03 mg rhTSH in 17 patients (aged 60-86 years, 12 women), who subsequently received 30 mCi 131-iodine 24 h after an identical rhTSH injection. TSH and free thyroxine (FT4) were measured at baseline and days 10, 30 and 90 after therapy. Thyroid volume was assessed by computed tomography at baseline and day 180. RESULTS: rhTSH, 0.03 mg, significantly increased mean 24-h thyroid RAIU from 25.8% +/- 10.3% to 43.3% +/- 8.4% (68% relative increase; t(16) = -8.43, P < 0.001). The proportion of patients overtly or subclinically hyperthyroid (TSH < 0.5 mU/l) decreased from 71% (12/17) at baseline to 19% (3/16) at 3 months. Mean serum FT4 peaked at slightly above normal range, 25.9 +/- 7.7 pmol/l (46% over baseline) and was 21% under baseline levels at 3 months. Mean estimated thyroid volume fell 34% from baseline to 6 months (170.0 +/- 112.8 to 113.1 +/- 97.5 ml; P < 0.01). Symptomatic relief, improved well-being, and/or reduction or elimination of antihyperthyroid medication were seen in 76% of patients. Three (18%) patients had transient neck pain or tenderness, or palpitations; one had transient asymptomatic thyroid enlargement; and three (18%) became hypothyroid by 3 months. CONCLUSIONS: Intramuscular rhTSH, 0.03 mg, followed 24 h later by 30 mCi 131-iodine, is a safe, effective and convenient treatment for MNG in elderly patients with comorbidities.

Intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke: initial Israeli experience.

BACKGROUND: Intravenous recombinant tissue plasminogen activator therapy within 3 hours of stroke onset is a proven effective treatment for acute ischemic stroke. OBJECTIVE: To assess the feasibility and safety of rt-PA therapy for reperfusion in routine clinical practice in Israel, in the setting of a dedicated stroke unit. METHODS: Consecutive patients presenting within less than 3 hours of stroke onset were evaluated by an emergency physician and the neurology stroke team. After brain computerized tomography, eligible patients were treated with intravenous rt-PA (0.9 mg/kg, maximum dose 90 mg) according to an in-hospital protocol corresponding to recommended criteria. Patients were admitted to the acute stroke unit. Safety and clinical outcome were routinely assessed. Recanalization was assessed by serial transcranial Doppler. RESULTS: The study group comprised 16 patients, mean age 61 years (range 47-80 years), male to female ratio 10:6, whose median baseline National Institutes of Health stroke scale was 13 (range 6-24). They were treated within a mean door-to-CT time of 39 minutes (range 17-62 min), door-to-drug time 101 minutes (range 72-150), and stroke onset-to-drug time 151 minutes (range 90-180). There was an early improvement within 24 hours (of > or = 4 points in the NIHSS score) in 7 patients (44%) and no early deteriorations. There were no protocol deviations, no symptomatic intracranial hemorrhages, and no major systemic hemorrhage within 36 hours of rt-PA treatment. Three asymptomatic hemorrhagic transformations of the infarct were noted on routine follow-up brain CT associated with neurologic improvement. Outcome data were comparable to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study. CONCLUSION: Intravenous rt-PA treatment within 3 hours of stroke onset in routine clinical practice in Israel is feasible and appears safe in the setting of a neurology stroke unit and team. Careful implementation of rt-PA therapy for selected patients in Israel is encouraged.

Serial quantitative diffusion tensor MRI of the premature brain: development in newborns with and without injury.

PURPOSE: To determine the change over time of the apparent diffusion coefficient (ADC) and relative anisotropy of cerebral water in a cohort of premature newborns serially studied near birth and again near term. MATERIALS AND METHODS: Newborns were classified as normal (N = 11), minimal white matter injury (N = 7), or moderate white matter injury (N = 5). RESULTS: ADC decreased significantly with age in all brain regions in newborns classified as normal and those with minimal white matter injury. ADC increased with age or failed to decline in widespread areas of white matter in newborns with moderate white matter injury. Anisotropy increased with age in all white matter regions in newborns classified as normal. Anisotropy did not increase in frontal white matter in those with minimal white matter injury, and in widespread white matter areas in those with moderate white matter injury. CONCLUSION: This study demonstrates that serial diffusion tensor magnetic resonance imaging scans of premature newborns can detect differences in white matter maturation in infants with and without white matter injury.