Background: The purpose of this study is to explore changes in blood-brain barrier (BBB) function and volumetry associated with Parkinson’s disease (PD) levodopa-induced-dyskinesia (LID). Methods: Twenty-six PD patients [matched pairs, 13 with LID (LID+) and 13 without (LID-)], performed high resolution 3D FSPGR MRI, applying a novel methodology developed for calculating delayed- enhancement-subtraction-maps, representing BBB function. Segmentation software calculated volumes of pre-determined brain structures and the mean BBB function was calculated for each structure. Comparisons between the LID+ and LID- paired patients and within patient, between the more and less affected hemisphere (MAH, LAH) and correlation tests with lateralized UPDRS motor scores were performed. Results: There were no significant differences in volumetric or BBB map characteristics between the matched LID+ and LID- patients regarding most brain areas except for the inferior parietal cortex (IPC) of the MAH that displayed a higher BBB disruption in LID+ vs. LID- patients. A positive correlation was found with the motor score of the side contralateral to the MAH(r = 0.58, p<0.038) among the LID+ patients. Conclusions: We demonstrated an association between slight BBB disruption in the IPC and LID in patients with PD using a new MRI methodology. As currently there is no known straightforward biological explanation for this positive finding, it might be genuine and novel, or spurious. Further studies to explore BBB functioning in the various stages of PD and its motor complications are needed, as well as further investigation of the IPC clinical importance and correction for epiphenomenon.

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.

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.

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.

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.

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 gamma (n= 5) which included cases that were affected by arachnoid cyst presence, and group delta (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.

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.

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.

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. (C) 2013 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

Rasmussen encephalitis is an inflammatory process affecting one cerebral hemisphere. The initial scans are normal or may in some cases show mild swelling and T2 hyperintensity of the involved cortical and subcortical areas, commonly in the frontal and temporal lobes. This is followed by progressive deterioration with gradual development of atrophy, predominantly in the affected hemisphere, but can also occur in the contralateral hemisphere. CT usually demonstrates asymmetrical atrophy, with or without brain infarcts. MRI can better demonstrate the atrophy and the abnormal tissue, before the formation of encephalomalacia on CT images. The cortical gray matter and subcortical white matter of the affected hemisphere are of abnormal high T2 signal. The basal ganglia may also be involved with progressive atrophy. There is typically no contrast enhancement and no hemorrhage. Diffusion tensor imaging shows increased ADC values and decreased fractional anisotropy (FA) in the affected hemisphere; there is also decreased perfusion as well as decreased metabolic activity on FDG-PET scans. MR spectroscopy typically shows a low NAA level, whereas elevated choline peak and lactate may also be found. Glutamine and glutamate (Glx peak) are usually increased, likely due to seizures. Atrophy and hypoperfusion of the contralateral cerebellar hemisphere (crossed cerebellar diaschisis) may also be present.

MRI shows a diffuse leukoencephalopathy with swelling of the white matter, involving both the supratentorial and the infratentorial compartments. There is a centripetal pattern of involvement, with relative sparing of the internal capsules and corpus callosum until later stages of the disease. The affected white matter appears T1 hypointense and hyperintense on T2-weighted images, with signal approaching that of the CSF, due to diffuse spongy degeneration. The same regions are bright on DWI and dark on ADC maps, consistent with reduced diffusivity of water, compatible with intramyelinic edema. The gray matter of the thalami and globi pallidi is also involved, whereas the caudate nuclei, putamina, and claustra are spared. There is no pathological enhancement of affected structures following contrast administration. Canavan disease has a pathognomonic appearance on proton MR spectroscopy with a marked increase of the NAA peak, as a result of its accumulation within the brain tissue. Other possible and nonspecific MR spectroscopy findings include decrease of choline and creatine, increased myo-inositol levels, and presence of lactate.

Cases 1 Hepatic Encephalopathy Maria Vittoria Spampinato 2 Neurofibromatosis Type 1 – UBOs Andrea Rossi 3 Carbon Monoxide Intoxication Benjamin Huang 4 Pantothenate Kinase-Associated Neurodegeneration (Hallervorden–Spatz Syndrome) Andrea Rossi 5 Methanol Intoxication Benjamin Huang 6 Wilson Disease Benjamin Huang 7 Hypoxic Ischemic Encephalopathy in Term Neonates Mariasavina Severino 8 Cryptococcosis Benjamin Huang 9 Gangliosidosis GM2 Mariasavina Severino 10 Leigh Disease Mariasavina Severino 11 Deep Cerebral Vein Thrombosis (DCVT) Benjamin Huang 12 Creutzfeldt–Jakob Disease (CJD) Benjamin Huang 13 Global Cerebral Anoxia in Mature Brain Maria Vittoria Spampinato and Zoran Rumboldt 14 Wernicke Encephalopathy Giulio Zuccoli 15 Amyotrophic Lateral Sclerosis Mauricio Castillo 16 Glutaric Aciduria Type 1 Mariasavina Severino 17 Subcortical Band Heterotopia Andrea Rossi 18 Bilateral Perisylvian Polymicrogyria (BPP) Mariasavina Severino 19 Lissencephaly Mariasavina Severino 20 Herpes Simplex Encephalitis Mauricio Castillo and Zoran Rumboldt 21 Limbic Encephalitis Mauricio Castillo 22 CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) Zoran Rumboldt 23 Megalencephalic Leukoencephalopathy with Subcortical Cysts Mariasavina Severino 24 Canavan Disease Andrea Rossi and Chen Hoffman 25 HIV Encephalopathy Zoran Rumboldt and Mauricio Castillo 26 RadiationandChemotherapy-Induced Leukoencephalopathy Maria Vittoria Spampinato 27 Leukoaraiosis (Microangiopathy) Alessandro Cianfoni 28 Periventricular Edema in Acute Hydrocephalus Alessandro Cianfoni 29 Hypoglycemia Benjamin Huang 30 X-linked Adrenoleukodystrophy (X-ALD) Mariasavina Severino 31 Periventricular Leukomalacia (PVL) Alessandro Cianfoni 32 Posterior Reversible Encephalopathy Syndrome (PRES, Hypertensive Encephalopathy) Maria Vittoria Spampinato and Zoran Rumboldt 33 Alexander Disease Mariasavina Severino 34 Metachromatic Leukodystrophy Andrea Rossi and Zoran Rumboldt 35 Neurodegenerative Langerhans Cell Histiocytosis (ND-LCH) Zoran Rumboldt and Andrea Rossi 36 Remote Cerebellar Hemorrhage Maria Gisele Matheus 37 Spontaneous Intracranial Hypotension Maria Vittoria Spampinato

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.

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.

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.