Neurodevelopmental outcome in children with congenital cytomegalovirus infection: A prospective multicenter cohort study.

BACKGROUND: Congenital cytomegalovirus infection (cCMV) is the most common congenital infection worldwide and is a major cause of neurodevelopmental impairment in children. At this point there are insufficient data on neurodevelopmental outcome of children with cCMV, both symptomatic and asymptomatic. AIM: This study aimed to describe the neurodevelopmental outcome in a large prospective cohort of children with cCMV. METHODS: All children with cCMV, included in the Flemish cCMV register, were eligible for this study. Data on neurodevelopmental outcome was available in 753 children. Data on neuromotor, cognitive, behavioral, audiological and ophthalmological outcome were analyzed. RESULTS: Neurodevelopmental outcome was normal in 530/753 (70,4 %) at any age of last follow-up. Mild, moderate and severe neurodevelopmental impairment was found in 128/753 (16,9 %), 56/753 (7,4 %) and 39/753 (5,2 %), respectively. Adverse outcome is found both in the symptomatic and asymptomatic children (53,5 % versus 17,8 %). Autism spectrum disorder (ASD) was diagnosed more often than in the general population in Flanders (2,5 % versus 0,7 %). Speech and language impairment was found in 2 %, even in absence of hearing loss. CONCLUSION: Both symptomatic and asymptomatic cCMV children are at risk of sequelae, with higher risk in case of first trimester infection. During follow-up of this population, special attention should be given to the audiological follow-up, the presence of hypotonia at young age, the possible higher risk of ASD and the risk of speech and language impairment even in absence of hearing loss. Our results emphasize the need for multidisciplinary neurodevelopmental follow-up of all cCMV infected children.

GIANT BASAL CELL CARCINOMA ON THE FOREHEAD AND WHY WE SHOULD PREVENT THEM - CASE REPORT.

Basal cell carcinoma (BCC) is the most prevalent malignancy, with rising incidence worldwide. Despite its naturally slow growth and initially low metastatic potential, it can cause significant morbidity and mortality when unrecognized, inadequately treated or poorly followed up. Authors present the case of a 61-year-old male with a 7-year history of multiple incomplete excisions of a “simple” BCC on the forehead. A CT scan of the head revealed an invasive mass (5.2 cm laterolateral x 4.0 cm craniocaudal) in the frontal area. There was no evidence of metastasis. Complete resection of the lesion and reconstruction was achieved in three stages. Final reconstruction was achieved using a left frontal fasciocutaneous flap. The secondary defect was closed with an advancement flap of the scalp and donor sites were covered using a split-thickness skin graft from the upper limb. This case demonstrates the necessity for vigilance in the approach to, diagnosis, treatment and follow-up of these skin neoplasms. The development of giant BCCs should be avoided at all costs. Increased size of BCCs corresponds with increased recurrence rate, metastatic rate, morbidity, mortality, treatment difficulties and overall costs.

Practitioner review: evidence-based practice guidelines on alcohol and drug misuse among adolescents: a systematic review.

BACKGROUND: Context-specific evidence-based guidelines on how to prevent and treat substance misuse among adolescents are currently lacking in many countries. Due to the time consuming nature of de novo guideline development, the ADAPTE collaboration introduced a methodology to adapt existing guidelines to a local context. An important step in this method is a systematic review to identify relevant high-quality evidence-based guidelines. This study describes the results of this step for the development of guidelines on adolescent alcohol and drug misuse in Belgium. METHODS: Rigorous systematic review methodology was used. This included searches of electronic databases (Medline, Embase, Cinahl, PsychInfo, and ERIC in June 2011), websites of relevant organizations, and reference lists of key publications. Experts in the field were also contacted. Included were Dutch, English, French, or German evidence-based practice guidelines from 2006 or later on the prevention, screening, assessment, or treatment of alcohol or illicit drug misuse in persons aged 12-18 years. Two independent reviewers assessed the quality of the guidelines using the AGREE II (Appraisal of Guidelines for Research and Evaluation) instrument. SCOPE: This overview provides a framework of current knowledge in adolescent alcohol and drug misuse prevention and treatment. RESULTS: This systematic review identified 32 relevant evidence-based guidelines on substance misuse among adolescents. Nine guidelines were judged to be of high quality; of which four had recommendations specifically on adolescents: one on school-based prevention, one on substance misuse prevention in vulnerable young people and two on alcohol misuse with specific sections for the adolescent population. There were few commonalities as guidelines focused on different target groups, professional disciplines and type and level of substance misuse. Evidence to support the recommendations was sparse, and many recommendations were based on expert consensus or on studies among adults. Also, the link between evidence and recommendations was often unclear. CONCLUSIONS: There are a substantial number of guidelines addressing substance misuse in adolescents. However, only four high-quality guidelines included recommendations specific for adolescents. The current level of evidence that underpins the recommendations in these high-quality guidelines is low.

Neonatal blood pressure monitoring: visual assessment is an unreliable method for selecting cuff sizes.

AIM: To compare current practice of cuff size selection for noninvasive blood pressure measurement in a single-centre, tertiary-level neonatal intensive care unit (visual assessment of bladder width/limb length closest to 2/3) with common recommendations for appropriate cuff selection. METHODS: Visual assessment of the appropriate cuff size ('2/3 rule') for upper arm, forearm and calf in 103 neonates (309 cuff selections) was compared with the following recommendations: (i) Method A - guidelines of the cuff manufacturer, (ii) Method B - cuff width/limb circumference ratio 0.44-0.60 and (iii) Method C - cuff width/limb length ratio closest to 0.66. RESULTS: The upper arm cuff size was correctly chosen in 84% of cases (Method A), 43% (Method B) and 56% (Method C). The forearm cuff size was correctly chosen in 94% of cases (Method A), 68% (Method B) and 54% (Method C). The calf cuff size was correctly chosen in 96% of cases (Method A), 72% (Method B) and 63% (Method C). CONCLUSION: The accuracy of selecting cuff size by visual assessment is low. Further research on accurate cuff selection for neonates, including at the forearm and calf, is warranted.

Mutations in SACS cause atypical and late-onset forms of ARSACS.

BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a complex neurodegenerative disorder caused by mutations in SACS. The phenotype consists of a childhood-onset triad of cerebellar ataxia, peripheral neuropathy, and pyramidal tract signs. OBJECTIVE: To provide more insight into the prevalence of SACS mutations and the variability of the associated phenotype. METHODS: Mutation screening of SACS by direct sequencing and multiplex amplicon quantification for detection of intragenic copy number variations in a cohort of 85 index patients with phenotypes suggestive for ARSACS. Additional short tandem repeat (STR) marker analysis was performed for haplotype sharing. RESULTS: In 11 families,18 new SACS mutations were found (12.9% of total cohort). Five patients displayed onset ages in adulthood, a feature not known to be associated with ARSACS. The remaining index patients displayed a classic early onset phenotype. Initial phenotypic presentation was atypical in several patients, obscuring the clinical diagnosis. A founder mutation in SACS was identified in 3 Belgian families. In one isolated patient, an intragenic SACS deletion of exons 3-5 was detected. Partial SACS deletions were not previously described. CONCLUSIONS: In this study, we enlarge the ARSACS phenotype and the underlying genetic spectrum of SACS mutations. Patients with ARSACS are more common than previously known and risk underdiagnosis due to late onset age and unusual presentation.

Progressive myoclonic epilepsy as an adult-onset manifestation of Leigh syndrome due to m.14487T>C.

BACKGROUND: m.14487T>C, a missense mutation (p.M63V) affecting the ND6 subunit of complex I of the mitochondrial respiratory chain, has been reported in isolated childhood cases with Leigh syndrome (LS) and progressive dystonia. Adult-onset phenotypes have not been reported. OBJECTIVES: To determine the clinical-neurological spectrum and associated mutation loads in an extended m.14487T>C family. METHODS: A genotype-phenotype correlation study of a Belgian five-generation family with 12 affected family members segregating m.14487T>C was carried out. Clinical and mutation load data were available for nine family members. Biochemical analysis of the respiratory chain was performed in three muscle biopsies. RESULTS: Heteroplasmic m.14487T>C levels (36-52% in leucocytes, 97-99% in muscle) were found in patients with progressive myoclonic epilepsy (PME) and dystonia or progressive hypokinetic-rigid syndrome. Patients with infantile LS were homoplasmic (99-100% in leucocytes, 100% in muscle). We found lower mutation loads (between 8 and 35% in blood) in adult patients with clinical features including migraine with aura, Leber hereditary optic neuropathy, sensorineural hearing loss and diabetes mellitus type 2. Despite homoplasmic mutation loads, complex I catalytic activity was only moderately decreased in muscle tissue. INTERPRETATION: m.14487T>C resulted in a broad spectrum of phenotypes in our family. Depending on the mutation load, it caused severe encephalopathies ranging from infantile LS to adult-onset PME with dystonia. This is the first report of PME as an important neurological manifestation of an isolated mitochondrial complex I defect.

Opsoclonus-myoclonus syndrome: a clinicopathological confrontation.

Opsoclonus-myoclonus syndrome (OMS), a movement disorder characterised by chaotic eye movements and myoclonus, is a rare clinical entity. We present two cases of opsoclonus-myoclonus syndrome of paraneoplastic origin. In the first patient the syndrome was associated with a breast carcinoma and in the second patient with a non small cell lung carcinoma. However none of the commonly associated antibodies were found in these cases. From the neuropathological findings from the first patient we find arguments that support the current hypothesis on the pathophysiology of OMS namely a dysfunction in brainstem and cerebellum. We conclude that in adults with OMS one has to be very suspicious of a possible neoplastic origin of the syndrome. The antibodies associated with some cases of OMS are thought to play a role in the pathophysiology of the syndrome although the exact immunologic mechanism remains unknown. Research into the neuropathological substrate of OMS yields a broad range of abnormalities in brain stem and cerebellum. However none of these findings seem to be pathognomonic. As for the possible therapy of OMS, several immunomodulating strategies can be used with varying success. At present there is no established standard therapy.

Central neurocytoma presenting with intraventricular hemorrhage: case report and review of literature.

We report a case of a 25 year old man presenting with acute headache, vomiting and nuchal rigidity. Computed Tomography (CT) scan and MRI without contrast showed a right ventricular hemorrhage surrounding a mass lesion. The tumor and hematoma were completely removed by neurosurgical transcortical-transventricular approach. Anatomopathological analysis revealed a central neurocytoma. Central neurocytoma seldom present with hemorrhage. We review 16 cases of neurocytoma with hemorrhage. It is important to recognize central neurocytoma as a cause of intraventricular hemorrhage, especially in adolescents and young adults. Outcome is often favorable when the tumor is completely removed. In some patients the clinical course is more aggressive and additional treatment such as radiotherapy, radiosurgery or chemotherapy is needed.

Failure of a recombinant Schistosoma bovis-derived glutathione S-transferase to protect cattle against experimental Fasciola hepatica infection.

The potential of a recombinant Schistosoma bovis 28-kDa glutathione S-transferase (rSb28GST) to protect cattle against Fasciola hepatica was tested in a vaccination trial. Thirty two calves were randomly divided into four groups of eight animals. Calves of the three vaccine groups received two intramuscular injections at 3 weeks interval, of 0.250mg rSb28GST in either aluminium hydroxide (Al(OH)(3)), Quil A, or PBS emulsified in an equal volume of Freund's complete adjuvant (FCA).Animals of the control group received injections of Al(OH)(3)/PBS only. All animals were challenged orally with a total of 360 metacercariae of F. hepatica, spread over 6 weeks. All groups of vaccinated animals produced measurable IgG antibody titers to rSb28GST after vaccination. Animals immunised with FCA adjuvanted vaccine had the highest and more durable antibody titers and only sera from this group recognised an approximately 24kDa protein band from F. hepatica, that is thought to be a F. hepatica GST. Despite a good antibody response differences in cumulative faecal egg output between the groups were not statistically significant. In addition, no significant difference was found between groups in terms of total worm numbers or percentage of immature flukes recovered at necropsy. In conclusion, the recombinant S. bovis 28kDa GST was not found to adequately protect cattle against experimental F. hepatica challenge, using either aluminium hydroxide, Quil A or FCA as adjuvant.

Postnatal cystic germinolysis and neonatal chronic lung disease: evaluation of risk factors and neurodevelopmental outcome.

UNLABELLED: Late neonatal onset of subependymal germinolysis in the caudothalamic groove has been associated with chronic lung disease. This clinical study had two objectives: (i) to clarify the link between chronic lung disease and germinolysis; and (ii) to evaluate the impact of germinolysis on neuromotor development of patients with chronic lung disease. Twenty-four patients with chronic lung disease and germinolysis were compared to 24 patients, matched for gestational age, with chronic lung disease but without germinolysis. There was no difference in the occurrence of perinatal risk factors for impaired cerebral development (small for gestational age at birth, impaired postnatal growth, postnatal steroid treatment, duration of mechanical ventilation) or in the presence of clinical markers potentially related to cerebral ischaemia (need for treatment of hypotension or poor perfusion, seizures, oliguria, hypocapnia). Both groups showed a high incidence of clinically significant developmental delay (mean Bayley Development Index of 72+/-23 [SD] in both groups), regardless of the presence or absence of germinolysis. CONCLUSIONS: We were unable to clarify the link between chronic lung disease and germinolysis, and it seems that germinolysis has no major impact on neurodevelopmental outcome of patients with chronic lung disease.

A comparison of ibuprofen and indomethacin for closure of patent ductus arteriosus.

BACKGROUND: Indomethacin is the conventional treatment for hemodynamically important patent ductus arteriosus in preterm infants. However, its use is associated with various side effects. In a prospective study, we compared ibuprofen and indomethacin with regard to efficacy and safety for the early treatment of patent ductus arteriosus in preterm infants. METHODS: We studied 148 infants (gestational age, 24 to 32 weeks) who had the respiratory distress syndrome and an echocardiographically confirmed, hemodynamically important patent ductus arteriosus. The infants were randomly assigned at five neonatal intensive care centers to receive three intravenous doses of either indomethacin (0.2 mg per kilogram of body weight, given at 12-hour intervals) or ibuprofen (a first dose of 10 mg per kilogram, followed at 24-hour intervals by two doses of 5 mq per kilogram each), starting on the third day of life. The rate of ductal closure, the need for additional treatment, side effects, complications, and the infants' clinical course were recorded. RESULTS: The rate of ductal closure was similar with the two treatments: ductal closure occurred in 49 of 74 infants given indomethacin (66 percent), and in 52 of 74 given ibuprofen (70 percent) (relative risk, 0.94; 95 percent confidence interval, 0.76 to 1.17; P=0.41). The numbers of infants who needed a second pharmacologic treatment or surgical ductal ligation did not differ significantly between the two groups. Oliguria occurred in 5 infants treated with ibuprofen and in 14 treated with indomethacin (P=0.03). There were no significant differences with respect to other side effects or complications. CONCLUSIONS: Ibuprofen therapy on the third day of life is as efficacious as indomethacin for the treatment of patent ductus arteriosus in preterm infants with the respiratory distress syndrome and is significantly less likely to induce oliguria.

Evaluation of different methods for the diagnosis of scabies in swine.

Scabies in pigs is still very common in many countries and can be detrimental to the productivity of pigs. However, correct diagnosis of the disease can preclude meaningful comparisons of results. Therefore, the objective of the present study was to determine, on 11 pig farms, the prevalence of scabies by determination of the presence of mites in ear scrapings, the dermatitis score, the SI and the detection of specific serum antibodies. For the latter an indirect ELISA technique was performed using a free-living mite as a source of antigen. A second objective was to compare the value of these different diagnostic tests. Four farms were positive for the presence of mites. Our study indicated that the SI of piglets is not reliable as a diagnostic tool for scabies (all values were below the threshold value of 0.4, even on farms that were positive for mites) but on the two farms with the highest prevalence of mites the SI was above the threshold for the finishers. However, the fact that sows from eight of the 11 farms investigated had a SI>0.4 would indicate that for sows either the SI is not very specific, or that a cut-off level of 0.4 is not relevant for this age group. On three of the four infected farms the ADS was higher than the cut-off value of 0.5, and on the fourth farm, where the ADS was only 0.43, individual carcasses with generalised dermatitis (score 2) were present. However, an ADS>0.5 did not always coincide with the presence of mites. On six farms, ODR values were indicative for the presence of Sarcoptes, and on three of these farms this was confirmed with positive ear scrapings. In conclusion, as determined by the detection of mites in pig ears, especially the results from the dermatitis scores seem to be useful in the diagnosis of scabies. The specificity of the other parameters is not sufficient, and therefore, the detection of mites should still be used to confirm scabies on a farm, in combination with other tools.

Control of gastrointestinal nematodes in first season grazing calves by two strategic treatments with eprinomectin.

A study was carried out to evaluate the effects of strategic early-season treatments with eprinomectin on first-season grazing calves exposed to strongyle infections on a naturally contaminated pasture. Two groups of first grazing season (FGS) calves were turned out in mid-May on two plots that were similar with respect to size and herbage infectivity. They grazed separately until housing at the end of October. One of these groups was given eprinomectin pour-on at turnout and 8 weeks later, while the other group served as untreated controls. The results showed that the treatments reduced gastrointestinal strongyle infections throughout the season as evidenced by lower faecal egg counts and serum pepsinogen levels compared with the controls. Furthermore, the results of herbage larval counts and postmortem worm counts in tracer animals demonstrated that the treatment had reduced herbage infectivity on the 'treated' plot. Finally, the chemoprophylactically treated calves had a better weight gain over the duration of the study than the untreated controls.

Evaluation of the persistent efficacy of doramectin and ivermectin injectable against Ostertagia ostertagi and Cooperia oncophora in cattle.

The persistent efficacy of doramectin and ivermectin injectable against moderate and high infection levels of Ostertagia ostertagi and Cooperia oncophora were evaluated in cattle. Calves were allocated to six groups of six animals. On Day 0 animals of Groups I1/I2 and D1/D2 were treated with 0.2mg/kg ivermectin and doramectin injectable, respectively. Animals of the C1, I1 and D1 groups received a daily (moderate) infection of 1000 L3 of O. ostertagi and 1000 L3 of C. oncophora, and animals of the C2, I2 and D2 groups received a daily (high) infection of 10,000 L3 of each species. The animals were infected for 21 days with both species, the infections with C. oncophora and O. ostertagi started from Days 8 and 15 post treatment, respectively. Animals were necropsied on Day 40. The calculation of the persistent activity of ivermectin and doramectin was based on the efficacy against the different developmental and adult stages of both parasites. The present study confirmed that infection levels may influence the duration of persistent efficacy of an anthelmintic. Doramectin had at the moderate infection level a persistent efficacy of at least 35 days against O. ostertagi and at least 28 days against C. oncophora; at the high infection dose persistent efficacy was somewhat shorter i.e. up to 33 days and approximately 28 days, respectively. The duration of persistent efficacy of ivermectin against O. ostertagi at the moderate infection level was between 14 and 25 days, at the high dose level up to 25 days. Persistent efficacy of ivermectin against C. oncophora could, at both infection doses, not be measured, with the present experimental design.

Neonatal focal temporal lobe or atrial wall haemorrhagic infarction.

AIMS: To describe two variants of infarction within the temporal lobe, associated with local matrix bleeding and mild to moderate intraventricular haemorrhage. METHODS: The files of 10 neonates, extracted from a sonographic study of 560 very low birthweight infants conducted between 1993 and 1997, were retrospectively examined. RESULTS: Seven lesions were located in the middle to posterior area of the temporal lobe, three others faced the atrium. All except two of those with a temporal site were VLBW infants with hyaline membrane disease. Except for one fatal case, intraventricular bleeding was mild to moderate. Computed tomograms or magnetic resonance imaging were used to illustrate the haemorrhagic nature of three lesions. Survivors of this so far undescribed entity who were followed up for more than 18 months did not have a uniform type of cerebral palsy but some scored in the low normal range on the Bayley Mental Development Index. One girl developed temporal lobe epilepsy. CONCLUSIONS: This pattern of injury seems to be one of venous infarction associated with temporal or para-atrial matrix haemorrhage. The temporal site fits the picture of venous infarction within the area drained by the inferior ventricular vein. A less constant lateral atrial vein, either draining into the basal or internal cerebral vein, is probably involved in the para-atrial lesion. Sonography may be the only practical tool currently available for detection in life.

Diagnosis of larval cyathostominosis in horses in Belgium.

Between October 1996 and May 1997, 94 horses which were suspected of being infected with strongyles were examined clinically, and samples of faeces were examined for strongyle eggs and cyathostome larvae (L4) and adults. Blood samples were monitored for total protein, albumin and beta-globulins. In 28 of the horses (30 per cent) cyathostome L4 and adults were detected in the faeces, and were significantly associated with the horses' condition, the occurrence of diarrhoea, with lower concentrations of total protein and albumin, and with higher percentages of beta-globulin. Thirty-four of the horses (36 per cent) were excreting strongyle eggs, but in these animals the associations were with high concentrations of total protein and albumin, and lower percentages of beta-globulin. The results showed that during the winter, a horse in poor condition which has diarrhoea, an albumin concentration less than 20 g/litre, and a ratio of albumin:globulin less than 0.7 is very likely to be infected with L4 and adult stages of cyathostomes.