Agenesis of the corpus callosum: an MR imaging analysis of associated abnormalities in the fetus.

BACKGROUND AND PURPOSE: Anomalies associated with callosal agenesis (ACC) found postnatally have been well documented. However, to our knowledge, no detailed MR imaging analysis of associated anomalies has been reported in a large cohort of fetuses with ACC. This study will assess those anomalies and compare them with postnatal cohorts of ACC, to identify associated fetal brain abnormalities that may give insight into etiology and outcome. MATERIALS AND METHODS: All cases of ACC diagnosed on fetal MR imaging during an 11-year period were retrospectively reviewed, including fetal MR imaging, postnatal MR imaging, and autopsy findings. Neurodevelopmental outcome was classified as poor in children with seizures and/or severe neurodevelopmental impairment or in cases of neonatal death. RESULTS: Twenty-nine cases of ACC were identified. Median gestational age was 26.14 weeks (range, 19.71-36.43 weeks). Twenty-three fetuses had delayed sulcation and/or too-numerous cortical infoldings (abnormal morphology). Fifteen fetuses had cerebellar and/or brain stem abnormalities. Fetal MR imaging findings suggested a genetic syndrome in 5 fetuses and an acquired etiology or genetic/metabolic disorder in 2 fetuses. Findings were confirmed in 8 cases with postnatal MR imaging, except for delayed sulcation and small vermis, and in 4 cases with autopsy, except for periventricular nodular heterotopia and abnormalities in areas not examined by autopsy. Neurodevelopmental outcome was good in 7 and poor in 9 children. Abnormal sulcal morphology and/or infratentorial abnormalities were present in those with poor outcome and absent in those with good outcome. CONCLUSIONS: ACC is infrequently isolated in fetuses. Abnormal sulcation is common and suggests more diffuse white matter dysgenesis in these fetuses.

Diffusion tensor imaging of the pyramidal tracts in infants with motor dysfunction.

OBJECTIVE: To determine if diffusion tensor imaging (DTI) metrics of the pyramidal tracts correlate with motor outcome in infants presenting with motor dysfunction. METHODS: DTI tractography of the pyramidal tracts was performed in 21 patients with clinical motor dysfunction who were less than 30 months of age and in 22 age-matched controls. We plotted tract-specific DTI metrics (fractional anisotropy, parallel diffusivity, transverse diffusivity, and mean diffusivity) against age for the controls and generated normative curves. For each patient, we calculated the deviation from the normative curves. Patients returned for a neurodevelopmental evaluation when they were over 36 months of age, and motor outcome measures were performed. We analyzed the association between normative deviation in DTI metrics and motor outcome measures using linear and logistic regression models. RESULTS: Normative deviation in fractional anisotropy and transverse diffusivity were significantly correlated with all measures of motor outcome. Lower fractional anisotropy and higher transverse diffusivity compared to controls were associated with worse motor outcome. Furthermore, children who were eventually diagnosed with permanent motor dysfunction had lower fractional anisotropy and higher transverse diffusivity compared with those whose motor dysfunction normalized. CONCLUSIONS: Diffusion tensor imaging metrics correlate with motor outcome in infants presenting with motor dysfunction. The identification of a quantitative imaging marker that can be applied to infants at the time of clinical presentation has implications for the evaluation of early motor dysfunction.

Diffusion tensor MR imaging tractography of the pyramidal tracts correlates with clinical motor function in children with congenital hemiparesis.

BACKGROUND AND PURPOSE: Children with congenital hemiparesis have greater asymmetry in diffusion parameters of the pyramidal tracts compared with control subjects. We hypothesized that the asymmetry correlates with the severity of hemiparesis and that diffusion metrics would be abnormal in the affected tracts and normal in the unaffected tracts. MATERIALS AND METHODS: Fifteen patients with congenital hemiparesis and 17 age-matched control subjects were studied with diffusion tensor MR imaging tractography. Hemipareses were scored as mild, moderate, or severe. We measured tract-specific diffusion parameters (fractional anisotropy, mean, and directional diffusion coefficients) of the pyramidal tracts. We compared tract-specific parameters and asymmetry between the right and left tracts of the differing severity groups and control subjects. RESULTS: We observed many different causes of congenital hemiparesis including venous infarction, arterial infarction, and polymicrogyria. Clinical severity of hemiparesis correlated with asymmetry in fractional anisotropy (P < .0001), transverse diffusivity (P < .0001), and mean diffusivity (P < .03). With increasing severity of hemiparesis, fractional anisotropy decreased (P < .0001) and transverse diffusivity (P < .0001) and mean diffusivity (P < .02) increased in the affected pyramidal tract compared with controls. Diffusion metrics in the unaffected tract were similar to those in the control subjects. CONCLUSION: Asymmetry in fractional anisotropy, transverse diffusivity, and mean diffusivity, as well as the degree of abnormality in the actual values of the affected pyramidal tracts themselves, correlates with the severity of motor dysfunction in infants and children with congenital hemiparesis from different causes. This suggests that abnormalities detected by diffusion tensor MR imaging tractography in the affected pyramidal tract are related to the functional ability of the affected pyramidal tract, regardless of the etiology of motor dysfunction.

The normal neonatal brain: MR imaging, diffusion tensor imaging, and 3D MR spectroscopy in healthy term neonates.

BACKGROUND AND PURPOSE: There is a lack of normative diffusion tensor imaging (DTI) and 3D MR spectroscopy (MRS) data in the early neonatal period. We report quantitative values from a cohort of healthy term neonates to serve as baseline data for studies assessing brain development and injury. MATERIALS AND METHODS: Sixteen healthy term neonates (median age, 7 days) were studied with spin-echo T1- and T2-weighted MR imaging, DTI, and 3D point-resolved spectroscopy sequence (PRESS) MRS without sedation on a 1.5 T scanner. Average diffusivity (D(av)), fractional anisotropy (FA), eigenvalues (EV), and metabolite ratios (N-acetylaspartate [NAA]/choline, lactate/choline) were calculated by automated processing in 7 brain regions. Neurodevelopment was assessed by blinded and validated neuromotor examinations and the Bayley II test at 3 and 14 months. RESULTS: Two neonates were excluded from the cohort: one had brain injury on T2-weighted imaging, and the other, who had normal MR imaging, showed mildly delayed cognition at 14 months. The mean DTI values of the remaining 14 neonates were between these ranges: D(av)=0.98-1.48 10(-3) mm(2)/s, FA=0.14-0.30, EV1=1.21-1.88, EV2=0.95-1.46, and EV3=0.77-1.24 (all x 10(-3) mm(2)/s). The NAA/choline ratio ranged between 0.58 and 0.73, and minimal lactate/choline (<0.15) could be detected in each neonate. All neonates exhibited clinically normal neuromotor status. CONCLUSIONS: Our study demonstrates the feasibility of obtaining high-quality quantifiable MR data in nonsedated healthy term neonates that can be used to study normal early brain development and as control data in studies of perinatal brain injury.

MR imaging, MR spectroscopy, and diffusion tensor imaging of sequential studies in neonates with encephalopathy.

BACKGROUND: Although the imaging, spectroscopic, and diffusion characteristics of brains of infants with neonatal encephalopathy have been described, the time course during which these changes evolve is not clear. The results of sequential MR imaging studies--including anatomic MR imaging, proton MR spectroscopy, and diffusion tensor imaging (DTI)--of 10 patients enrolled prospectively in a study of neonatal encephalopathy are reported to help to clarify the time course of changes in different brain regions during the first 2 weeks of life. METHODS: Ten neonates were prospectively enrolled in a study of the evolution of MR findings in neonatal encephalopathy and were studied 2 (8 patients) or 3 (2 patients) times within the first 2 weeks of life. The MR examination included spin-echo T1 and T2-weighted images, DTI, and long echo time (288 milliseconds) proton MR spectroscopy. Diffusion parameters (diffusivity [D(av)], fractional anisotropy [FA], and individual eigenvalues) were calculated for 10 1-cm2 regions of interest in each hemisphere that were placed based on anatomic landmarks. D(av) and FA were then measured manually in the same areas on a workstation. Metabolite ratios (NAA/Ch, Cr/Ch, Cr/NAA, Lac/Ch, and Lac/NAA) were calculated in 7 regions of interest. Imaging appearance, diffusion parameters, and metabolite ratios were then evaluated longitudinally (comparing with other studies on the same patient at different times) and cross-sectionally (comparing all studies performed on the same postnatal day). RESULTS: In most of the patients a characteristic evolution of DTI and MR spectroscopy parameters was seen during the first 2 weeks after birth. Although the anatomic images were normal or nearly normal on the first 2 days after birth in most patients, abnormalities were detected on DTI (both visually and by quantitative interrogation of D(av) maps) and proton MR spectroscopy (abnormal metabolite ratios). These parameters tended to worsen until about day 5 and then normalize, though in several patients abnormal metabolite ratios persisted. Of interest, as areas of abnormal diffusivity pseudonormalized within one region of the brain they would develop in other areas. Therefore, the pattern of injury looked very different when imaging was performed at different times during this evolution. CONCLUSION: Patterns of injury detected by standard anatomic imaging sequences, DTI sequences, and proton MR spectroscopy varied considerably during the first 2 weeks after injury. The appearance of new areas of reduced diffusion simultaneous with the pseudonormalization of areas that had reduced diffusion at earlier times can result in an entirely different pattern of injury on diffusivity maps acquired at different time points. Awareness of these evolving patterns is essential if studies are performed and interpreted during this critical period of time.

Periodic reappearance of bovine herpesvirus type 4 DNA in the sera of naturally and experimentally infected rabbits and calves.

A BHV-4 specific nested PCR was used for the detection of viral DNA in serum samples of rabbits and calves. All animals were followed up for 62 days, blood samples were taken for PCR studies every second day. Maternal infection of calves resulted in the repeated regular reappearance (10-14 days) of the virus (DNA) in serum samples. When PCR positive five-day-old calves were infected with tissue culture adapted virus, the reappearance of the DNA in the serum was shown to be irregular, nevertheless, DNA peaks reappeared during the whole observation period. A PCR negative calf infected at the age of 60 days was found to possess viraemia until p.i.d. 32. In rabbits treated intravenously with BHV-4 the inoculum or a primary viraemia was detected at p.i.d. 2-3 and p.i.d. 14-16. Published data on human herpesviruses suggest, that the target cells might be a pluripotent stem cell population of the bone marrow and differentiated virus-infected cells destroyed by the immune system might be the source of viral DNA detected in the serum. Frequency of DNA reappearance was depended on the age of the infected animals but not on the inoculated amount of BHV-4. The described phenomenon might be part of BHV-4 infection of very young animals.

PCR studies on the potential sites for latency of BHV-4 in calves.

The aim of the study was to examine various tissues of experimentally infected calves for the BHV-4 genome so as to detect in which cells the virus persists during the latent phase of the infection. The presence of the bovine herpesvirus type 4 genome was detected by a nested PCR in a variety of tissues collected from two susceptible calves experimentally infected 62 days earlier. Mild clinical signs of bronchitis, an elevated body temperature for 2-3 days, and a slightly increased number of blood leukocytes were observed in both inoculated calves. BHV-4 was demonstrated in seven samples from the 12 different parts of the nervous system tested from each calf (29.1%), from the cornea, from lymph nodes near to the inoculation site, from the gallbladder and from the bone marrow. Thus a member of the predominantly lymphotropic Gammaherpesvirinae subfamily was detected in neural tissue and other organs that have never been associated with persistence.

[Use of studies on genome polymorphism in follow up after allogenic bone marrow transplantation]. / Genom polimorfizmus vizsgálatok alkalmazása allogén csontvelö-transzplantációt követöen.

The study of structures polymorphic in size found in the human genom (the VNTR loci) enables us to differentiate two individuals or--after bone marrow transplantation--to detect the simultaneous presence of two genoms in patients' blood or marrow. The existence of mixed chimerism may influence the therapy. The authors have screened 54 patients, transplanted in their Institute, and their donors by determination of four polymorphic loci. Informative marker was found in 43 cases. The bone marrow transplantation immunotherapy of 29 patients could be followed over 2-36 months. To increase the sensitivity of the polymerase chain reaction method used, the authors introduced the blotting/hybridization steps using isotop labeled repetitive sequences. The results are presented in comparison with literature data.

Histological studies of bovine herpesvirus type 4 infection in non-ruminant species.

The pathology of bovine herpesvirus type 4 (BHV-4) infection was studied in cats, rabbits and guinea pigs. Twenty kittens, twenty-two rabbits and ten guinea pigs, some treated with glucocorticoid-were inoculated with a BHV-4 strain of feline origin, via various routes of inoculation (conjunctival, intranasal, peritoneal). Clinical signs were recorded. After euthanizing at different post inoculation days macro- and microscopic changes were observed by necropsy and in hematoxylin-eosin stained histological sections. The presence of the virus in organs was detected by immunohistochemistry and a nested PCR assay. Inclusion bodies and monoclonal antibody-stained cells were found in the conjunctiva, trachea, lungs, spleen and lymph nodes. Most of the lesions were localized to the respiratory and the immune system. The macro- and microscopic lesions and clinical signs were more severe in kittens and guinea pigs. The histological data indicated that cats, especially kittens, were susceptible for BHV-4 and the infection was not confined to the urinary bladder.

Studies of in vivo distribution of bovine herpesvirus type 4 in the natural host.

The in vivo distribution of bovine herpesvirus type 4 (BHV-4) was examined by testing nasal and conjunctival exudates, peripheral blood leukocytes, and various organs of experimentally infected calves. For virus detection, a nested PCR assay, virus isolation, and immunohistochemistry were applied. The nervous system and the muscles were free of viral DNA. Liver and intestinal lymph nodes contained low amounts of virus (less than two copies per 1 microgram of cellular DNA). Intestinal, tonsil, thymus, and kidney tissues contained more viral DNA copies (5 to 50 copies per 1 microgram of cellular DNA). The highest amounts of BHV-4 DNA (50 to 500 copies per 1 microgram of cellular DNA) were found in the spleen, lungs, trachea, and nasal epithelium. Amplification of DNA from blood lymphocytes through postinoculation (p.i.) day 48 proved that the virus started to replicate in these cells immediately after inoculation of the calves and that intensive virus growth took place during the 7 to 8 weeks of the infection. The number of virus-infected lymphocytes reached the maximum on p.i. days 22 to 26 and slowly declined thereafter. Virus-infected cells were found only in the spleen on p.i. day 48 by immunohistochemistry. Western blotting (immunoblotting) detected signs of an immune response against 9 of the 29 BHV-4 proteins.

Restriction endonuclease analysis of Hungarian bovine herpesvirus isolates from different clinical forms of IBR, IPV and encephalitis.

The DNA of thirty-three Hungarian bovine herpesvirus isolates originating from cattle with various clinical symptoms were compared by restriction endonuclease analysis using HindIII, EcoRI and BstEII enzymes. The EcoRI and HindIII cleavage patterns were similar to those of isolates studied in other countries. Based on the cleavage patterns, the Hungarian isolates could be assorted into groups and subgroups according to the classification system proposed by Metzler et al. (1985, 1986). Based on a new BstEII cleavage pattern observed in group 1, the establishment of two new subgroups, 1a and 1b, were proposed. Three isolates belonged to subgroup 1a, sixteen to 1b, seven to 2a, five to 2b, and one to group 3, which has recently been reclassified as BHV-5. Additionally, one of the isolates showed a mixed cleavage pattern of 1a and 1b. However, no strict correlation was found between the different clinical forms and the established DNA fingerprint groups. There was no evidence of a change in the prevalence of the different genotypes when comparing isolates collected at different times of a 24-year period.

Study of bovine herpesvirus type 1 strains with monoclonal antibodies.

Fourteen strains of bovine herpesvirus type 1 (BHV-1, IBRV) representing all three groups of BHV-1 (BHV-1.1, BHV-1.2, BHV-1.3) were studied by ELISA using 106 monoclonal antibodies (Mabs) produced against BHV-1. On the basis of the ELISA, the Mabs could be divided into three groups. The first group (40 Mabs, 38%) reacted with all strains, the second group (43 Mabs, 41%) with the respiratory and genital strains (BHV-1.1 and BHV-1.2) while the third group (23 Mabs, 22%) only with the respiratory strains. Only 5 out of the antibodies neutralized respiratory and genital strains, and none of them neutralized the encephalitogenic strains (1.3). Three Mabs selected from each of the 3 groups, and the above five neutralizing strains were studied by Western blot. Antibodies of groups 1 and 3, and two neutralizing antibodies bound to a 90k protein (gpIII), whereas members of group 2 and 3 neutralizing antibodies reacted with a 74k and a 130k protein (both gpl). The results indicate that reactivity with monoclonal antibodies is as suitable for the classification of BHV-1 strains as is restriction endonuclease (RE) analysis but it cannot distinguish between subgroups within the groups.

[Analysis of radiographic changes in the cervical spine in rheumatoid arthritis]. / A nyaki gerinc röntgen tüneteinek elemzése rheumatoid arthritisben.

At the outpatient department of rheumatology 100 patients having definitive or classic rheumatoid arthritis (RA) were examined and their cervical spine was radiographed with traditional X-ray technique. Correlation between roentgen signs and some parameters of the patient and of the disease was processed by regression analysis. The presence of the rheumatoid factor and second line drug therapy did not influence radiographic changes. Degenerative roentgen signs showed a linear correlation with the RA functional capacity and the duration of cervical complaints, and an exponential correlation with the duration of disease and the age of the patient. There was a linear correlation between osteoporosis and all the parameters examined. Inflammatory radiographic changes showed an exponential correlation with functional capacity and duration of cervical complaints, and a linear correlation with the duration of illness and the age of the patient. Symptoms of patients never treated with steroids was more severe than of those receiving short steroid therapy, but less serious than of those who had taken steroids for a long time (for longer than 10 years).

Arsenic in drinking water and mortality in the Southern Great Plain, Hungary.

Arsenic distribution has been found in drinking waters. A connection between arsenic and other constituents of water was determined. Close positive correlation was found between arsenic and humic substances over most of the study area. In two smaller areas, there was no correlation between arsenic and humic substances. In these waters, the arsenic distribution is not controlled by organic matter, but by other factors which need further investigations.Examination of mortality in the populations consuming water containing levels of arsenic above and below that permitted did not show any significant differences in standardised mortality ratio (SMR) from all causes of death for both male and female. The SMR from the main causes of death - diseases of the circulatory system and neoplasms - shows controversial results for males and females.

A heteroploid permanent cell line originating from embryonic calf thyroid supporting the replication of all known bovine adenovirus serotypes.

An embryonic calf thyroid cell culture was established as a permanent heteroploid cell line, which is now in its 150th subculture. It allowed replication of all nine bovine adenovirus serotypes at its 15th as well as its 60-150th passages. All viruses induced typical cytopathic effects. Yields obtained on the permanent calf thyroid line were, on average, 0.8 log10 lower than those obtained on primary calf testicle cells.

DNA restriction enzyme analysis of a bovine herpesvirus 1 strain isolated from encephalitis in Hungary.

The DNA of a bovine herpesvirus 1 (BHV-1) strain isolated from calf encephalitis in Hungary was analysed with restriction enzymes. The cleavage pattern of the encephalitis strain Na/67 differed from those of all the other Hungarian BHV-1 isolates investigated so far. The EcoRI and HindIII cleavage patterns of virus strain Na/67 were found to be similar to the patterns of two other encephalitis strains (N569 and A663 from Australia and Argentina, respectively) characterized earlier. Strain Na/67 is the first isolate in Europe which showed the restriction enzyme pattern of BHV-1.3 previously supposed to be characteristic of encephalitis strains.

Molecular cloning of DNA from a bovine herpesvirus 1 strain isolated in Hungary.

Molecular cloning of the HindIII fragments of bovine herpesvirus 1 (BHV-1) strain HB144, isolated from infectious bovine rhinotracheitis (IBR) in Hungary, and of an infectious pustular vulvovaginitis (IPV) reference strain (K22) is reported. So far 52% of the IBR viral genome and 28% of the IPV viral genome have been cloned. The analysis of differences between the strains is currently in progress.

A new subgroup 2 bovine adenovirus proposed as the prototype strain 10.

A slowly growing subgroup 2 bovine adenovirus (BAV) strain designated Ruakura 78-5371 was isolated from a yearling heifer with systemic adenovirus infection. Cross neutralization tests and restriction endonuclease analysis of the viral DNA showed the virus to be distinct from the other 9 recognised types of BAV. It is proposed that this strain should be regarded as the prototype strain of the new type BAV-10.

Bovine herpesvirus 1: rapid diagnosis of infection by direct filter hybridization.

Direct filter hybridization (DFH) was applied as a simple method of nucleic acid hybridization to diagnose bovine herpesvirus 1 (BHV-1) infection without previous purification of nucleic acids from the specimens. The DNA of BHV-1 was cleaved with the restriction endonuclease Pst I and randomly cloned into pKH47 plasmids. The clones were labelled with 32P or biotin and selected on uninfected and infected cells for the highest specific activity to detect BHV-1 infection. Two clones, which detected about 10 infected cells, were selected for the diagnosis of BHV-1 in cattle. On specimens collected during experimental and natural disease, the DFH showed to be in concordance with the standard method of virus isolation. This simple hybridization technique proved to be a sensitive and rapid alternative to virus isolation. Specific diagnosis of BHV-1 infection can be made even in simply equipped laboratories within 10 h.