Cortical malformations: A significant cause of paediatric neurological morbidity

Disorders of cortical development are a significant cause of epilepsy, developmental delay and congenital neurological deficits in children of all ages. Disruption of neuronal proliferation, differentiation, migration and organization during the middle trimester are recognized as the basis of most of these disorders. With advances in magnetic resonance imaging and increasing recognition of the characteristic radiological appearance of these lesions, a variety of lesions are now described. Furthermore, detailed clinical and genetic studies have lead to the recognition of clinicopathological syndromes of cortical maldevelopment with specific modes of inheritance. Our understanding of these disorders is increasing rapidly and will continue to do so with improvements in neuroimaging, advances in developmental neurobiology and heightened clinician awareness.     

Human herpesvirus-6 and -7 infections in transplantation

Human herpesvirus-6 (HHV-6) and human herpesvirus-7 (HHV-7) are ubiquitous in the human population and cause exanthem subitum, a benign disease seen in infancy. The viruses remain latent in the body after primary infection, and reactivate in immunocompromised patients. HHV-6 infection occurs in nearly 50% of all bone marrow and in 20-30% of solid-organ transplant recipients, 2-3 weeks following the procedure. It has been suggested that the viral infection and activation result in clinical symptoms, including fever, skin rash, pneumonia, bone marrow suppression, encephalitis, and rejection. In order to understand the viral infection in greater detail, several studies investigating the route of viral transmission and diagnostic procedures have been carried out. In contrast to studies of HHV-6 infection in organ-transplant recipients, the number of studies examining HHV-7 infection in these patients is limited. According to several recent studies, HHV-7 may act as a cofactor for cytomegalovirus disease in organ-transplant recipients.     

Pain in children with significant neurological impairment.

The pain experience in the child with a significant neurological impairment is complex and confusing, and it raises many questions about the very nature of pain itself. Early work in this field suggests that the pain experience may be blunted. The neurological impairment associated with conditions such as cerebral palsy may alter the neurological system and hence the ability to comprehend and communicate pain; there is no evidence to date that this reflects true pain insensitivity or indifference. From recent work, the emerging body of evidence supports a relationship between the pain system and the motor, sensory, and autonomic systems and demonstrates how alterations to these systems may have a profound and unique impact on the pain experience. Beyond the altered neurological substrate, communication disabilities and social/environmental factors also seem to alter the pain experience. Establishing a clear pain history, including baseline information of child-specific patterns of behaviors and ongoing comparative use of this information over time, can provide clinically meaningful measures. Pain management should be directed at the underlying sources of pain and should include the analgesic ladder for everyday pain, opioids for acute/procedural pain (+/- benzodiazepine adjuvants), and antispasticity medications for high tone. With appropriate monitoring, demand and regional analgesic techniques can provide effective and safe postoperative pain control. The lack of basic and clinical knowledge in this field, however, adds another challenge to the clinician.     

Human herpesvirus-6 and -7 in pediatric stem cell transplantation

BACKGROUND: Human herpesvirus-6 (HHV-6) and -7 (HHV-7) may reactivate with immunosuppression and cause symptoms varying from subclinical to severe organ manifestations. The presence of HHV-6 and -7 and their possible association with clinical problems among pediatric recipients of stem cell grafts was studied in a single institution setting between November 1999 and December 2001. PROCEDURE: A total of 60 patients, mean age 8.5 years, were transplanted: 2/3 received allogeneic grafts and 1/3 autologous stem cell rescue. The presence of HHV-6 and -7 was studied in blood by polymerase chain reaction (PCR) (HHV-6) and antigenemia (HHV-6 and -7). RESULTS: Both HHV-6 and -7 were frequently present in the blood of stem cell graft recipients. No significant difference in the incidence of HHV-6 or -7 reactivations between the allogeneic and autologous patients nor recipients of sibling or unrelated donor (URD) grafts was observed. HHV-6 antigenemia was associated with fever, rash, and delayed engraftment. Among symptomatic patients two cases of encephalitis were encountered with both having HHV-6 detectable in their cerebrospinal fluid (CSF) by PCR. CONCLUSIONS: HHV-6 and -7 seem to be common in blood both pre- and post-transplant among pediatric recipients of stem cell grafts. Prolonged reactivations appear to correlate with clinical symptoms such as fever, rash, and bone marrow suppression in the post-stem cell transplant setting (SCT), but severe complications are rare. Transient reactivations appear to be of very limited clinical significance.     

Seasonality of sudden infant death syndrome in mainland Britain and Ireland 1985-95

AIM: To compare an ultrasonic height measuring device (Gulliver) with mechanical stadiometry and the classical "book and tape measure" method. METHODS: Blinded duplicate measurements of height were made on each of 14 children by a pair of observers using a stadiometer (H) and Gulliver (G). Height was measured on a further 18 children by parents and an auxologist using Gulliver and the book and tape method (TM), and the results were compared with those obtained with a single stadiometry measurement. Finally, measurement of a rigid metal box was made on 10 occasions by the three methods. RESULTS: In the group of 14 children, the mean difference (range) in height (H minus G) was +2.8 cm (+0.5 to +4.55 cm), with H giving a systematically higher value in 276 of 280 individual measurements. In the group of 18 children, height by H was greater than by G or TM in 47 of 52 individual measurements. The mean (SD) height of the box by H (61.60 (0.07) cm) was greater than by G (60.96 (0.15) cm; p < 0.001) but not TM (61.4 (0.16) cm; p > 0.05). G and TM produced three times less reliable estimations of height than H, but with a large difference in cost, and there was evidence of systematic underrecording of height by 0.5 cm with G. CONCLUSIONS: Stadiometry is precise and reproducible, and can detect true changes in height over one month periods in mid-childhood, and should remain the standard way of observing growth. The book and tape method can produce clinically acceptable quarterly estimations of height that can be performed in the home.     

Presenting features of inflammatory bowel disease in Great Britain and Ireland.

BACKGROUND: Reports from individual referral centres suggest that a significant proportion of children with inflammatory bowel disease (IBD) present after prolonged delays and with impaired growth. AIMS: To prospectively document the presenting features, delay in presentation, disease localisation, and growth in newly diagnosed cases of IBD. METHODS: For 13 months, between June 1998 and June 1999, 3247 paediatricians, adult gastroenterologists, and surgeons across the UK and Ireland were prospectively surveyed each month and asked to report every newly diagnosed case of childhood IBD. RESULTS: A total of 739 new IBD cases aged less than 16 years were identified. Only one quarter of Crohn's disease (CD) cases presented with the "classic triad" of diarrhoea, weight loss, and abdominal pain; nearly half did not report diarrhoea. The median delay from onset of symptoms to diagnosis was 5 months (mean 11 months), with one fifth having symptoms of more than one year. Delays were most common in CD and in younger children. Short stature was noted only in those with CD and not with ulcerative colitis. One fifth of CD cases had disease activity in the jejunum and this group had significantly reduced stature. Ileo-colonic involvement was documented in most CD cases, with only a small minority having isolated ileal or isolated colonic disease. Pan-colitis was reported in most UC cases, with very few having only an isolated proctitis. CONCLUSIONS: Many children are diagnosed after prolonged delays and have growth failure. Improved knowledge of the presenting features of IBD, and earlier investigation of suspected cases, may help reduce the delays noted.     

Human herpesvirus-6 and -7 infections in children: agents of roseola and other syndromes

Human herpesvirus-6 (HHV-6) and -7 (HHV-7) infections typically are silent or manifested as mild febrile illnesses including classic roseola. In addition, case reports and epidemiologic data support the rare occurrence of HHV-6 encephalitis in immunocompromised as well as immunocompetent subjects. Although many other diseases have been putatively associated with HHV-6 or HHV-7, these associations are not well documented due to small numbers, use of tests incapable of distinguishing latent from replicating virus, potential virus cross-reactivity, or contradictory results. Further careful studies are needed to confirm these disease associations. Laboratory tests for diagnosing active HHV-6 and HHV-7 infections include virus culture, antigen detection, and polymerase chain reaction of cell-free biologic fluid. Although HHV-6 and HHV-7 are inhibited by several antiviral drugs in the laboratory, including ganciclovir and foscarnet, no clinical trials have assessed their benefit. Nevertheless, treatment may be considered for patients with serious HHV-6- or HHV-7-associated disease confirmed with accurate virologic tests.     

Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric Surveillance Unit Surveys, 1993 94 and 2001-02.

OBJECTIVE: To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988-90 survey (VKDB-90). DESIGN: Two 2-year surveys conducted during 1993-4 (VKDB-94) and 2001-02 (VKDB-02). SETTING: Data collected from all consultant paediatricians in Great Britain and Ireland. PATIENTS: All infants presenting with bleeding resulting from vitamin K (VK) deficiency. MAIN OUTCOME MEASURES: Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features. RESULTS: Compared with previous studies, VKDB-02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long-term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast-fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB-90, 10 of 32 in VKDB-94 and 4 (because of parental refusal) of 7 in VKDB-02. Seven received one oral dose of VK in VKDB-90, 16 in VKDB-94 and none in VKDB-02. Underlying liver disease was found in six cases in VKDB-90, 12 in VKDB-94 and one in VKDB-02. CONCLUSIONS: In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast-fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.     

Presenting features of inflammatory bowel disease in Great Britain and Ireland

Background: Reports from individual referral centres suggest that a significant proportion of children with inflammatory bowel disease (IBD) present after prolonged delays and with impaired growth. Aims: To prospectively document the presenting features, delay in presentation, disease localisation, and growth in newly diagnosed cases of IBD. Methods: For 13 months, between June 1998 and June 1999, 3247 paediatricians, adult gastroenterologists, and surgeons across the UK and Ireland were prospectively surveyed each month and asked to report every newly diagnosed case of childhood IBD. Results: A total of 739 new IBD cases aged less than 16 years were identified. Only one quarter of Crohn''s disease (CD) cases presented with the "classic triad" of diarrhoea, weight loss, and abdominal pain; nearly half did not report diarrhoea. The median delay from onset of symptoms to diagnosis was 5 months (mean 11 months), with one fifth having symptoms of more than one year. Delays were most common in CD and in younger children. Short stature was noted only in those with CD and not with ulcerative colitis. One fifth of CD cases had disease activity in the jejunum and this group had significantly reduced stature. Ileo-colonic involvement was documented in most CD cases, with only a small minority having isolated ileal or isolated colonic disease. Pan-colitis was reported in most UC cases, with very few having only an isolated proctitis. Conclusions: Many children are diagnosed after prolonged delays and have growth failure. Improved knowledge of the presenting features of IBD, and earlier investigation of suspected cases, may help reduce the delays noted.     

Variations in initial assessment and management of inflammatory bowel disease across Great Britain and Ireland.

BACKGROUND: There are no published data from Great Britain and Ireland detailing the initial management of children with inflammatory bowel disease (IBD). AIMS: To prospectively record the initial investigation and treatment of children aged less than 16 years with newly diagnosed IBD. METHODS: For 13 months, between June 1998 and June 1999, 3247 paediatricians, adult gastroenterologists, and surgeons across the UK and Ireland were prospectively surveyed each month and asked to report every newly diagnosed case of childhood IBD. Reporters subsequently completed a postal questionnaire about each case. RESULTS: A total of 739 new IBD cases were reported from 172 institutions. Significant variations were observed in the investigation and treatment of these cases, when examined by number of cases reported per institution, or by the specialists providing care. There were wide regional variations in the proportion of children having access to paediatric gastroenterology services. Overall, one third of children received care from an adult service, and a tenth care exclusively from an adult gastroenterologist. Children with Crohn's disease who had some or all of their care from adult services were more likely to receive systemic steroids and less likely to receive dietary therapy; those with ulcerative colitis were more likely to receive rectal steroids and to have surgery. Height and weight were also less likely to be recorded in those whose care involved adult services. CONCLUSION: Current specialist provision, and initial investigation and treatment of IBD, is heterogeneous. Optimisation of care is likely to be achieved by greater access to specialist paediatric gastroenterology services for all those with suspected IBD.     

Hospital morbidity pattern in children under 1 year of age born in Sheffield 1975-6.

The morbidity pattern, based on hospital admissions for a complete year''s cohort of all children born in Sheffield 1975-6, was studied. In many children the diagnosis given on admission had changed by the time they were discharged from hospital. About one-quarter of children under age 6 months were admitted for social reasons. Despite a decreasing birth rate the admission rate had increased, with an overall admission rate of 11.2% of all births. The rates and ages at which children are admitted varied greatly according to the month of birth. This is an important factor if cohort studies from different places are being compared.     

Invasion by human herpesvirus 6 and human herpesvirus 7 of the central nervous system in patients with neurological signs and symptoms.

METHODS: A total of 43 children with neurological signs and symptoms were enrolled in the study. All children were suspected of having meningitis, and lumbar punctures were performed. Human herpesvirus 6 (HHV-6) and HHV-7 DNA was detected in cerebrospinal fluid (CSF) and peripheral blood mononuclear cells (PBMC) by nested polymerase chain reaction. RESULTS: Most patients had detectable serum antibody to both HHV6 and 7. HHV6 DNA was detected in PBMC of 15 patients and in CSF cell pellet of seven. Corresponding figures for HHV7 were 28 and 6.2/7, and 5/6 with CSF viral DNA also had it in PBMC, respectively. No viral DNA was detected in CSF supernatants. The seven HHV6 CSF viruses were all variant B. CONCLUSION: These data suggest that HHV-7 may invade the CNS.     

Obstetrical condition and neonatal neurological morbidity. An analysis with the help of the optimality concept

In order to increase understanding of the origin of neonatal neurological morbidity, the relationship between the obstetrical and neonatal neurological conditions was studied in a 3-year cohort containing 3162 singleton infants. The infants were neurologically examined at term age according to the technique described by Prechtl. Obstetrical data were documented extensively. Prechtl's optimality concept was applied in the analysis. A statistically significant relationship was found between the obstetrical and neo-natal neurological optimality scores. There was no sex difference in the obstetrical optimality, whereas there was in the neurological optimality, to the advantage of the girls. It could be shown that obstetrical conditions such as acidemia, preterm birth and intrauterine growth retardation have a stronger relationship to neurological morbidity when the accompanying obstetrical optimality is lower. In obstetrical practice the application of the optimality concept to obstetrical and neurological data is a helpful complementary refinement.     

Vitamin K deficiency bleeding in Great Britain and Ireland: British Paediatric Surveillance Unit Surveys, 1993 94 and 2001-02

Objective

To conduct and report monitoring of vitamin K deficiency bleeding (VKDB) in Great Britain and Ireland following the 1988–90 survey (VKDB‐90).

Design

Two 2‐year surveys conducted during 1993–4 (VKDB‐94) and 2001–02 (VKDB‐02).

Setting

Data collected from all consultant paediatricians in Great Britain and Ireland.

Patients

All infants presenting with bleeding resulting from vitamin K (VK) deficiency.

Main outcome measures

Incidence of VKDB, related mortality/morbidity and VK prophylaxis recommended/received, noting predisposing features.

Results

Compared with previous studies, VKDB‐02 found fewer cases of VKDB (RR: 0.27 (95% CI: 0.12 to 0.59), p<0.001) with no deaths, no long‐term morbidity and reduced incidence among those receiving any oral dosing (RR: 0.24 (95% CI: 0.06 to 1.01), p<0.059). Breast‐fed infants accounted for the vast majority of cases. The number receiving no prophylaxis fell consecutively over time: 20 of 27 in VKDB‐90, 10 of 32 in VKDB‐94 and 4 (because of parental refusal) of 7 in VKDB‐02. Seven received one oral dose of VK in VKDB‐90, 16 in VKDB‐94 and none in VKDB‐02. Underlying liver disease was found in six cases in VKDB‐90, 12 in VKDB‐94 and one in VKDB‐02.

Conclusions

In the most recent survey, the incidence of VKDB was about one third that in the two earlier studies. Late onset VKDB remains virtually confined to breast‐fed infants who have received either no VK or just one oral dose. The effectiveness of oral prophylaxis regimens has improved over the last 15 years, but parental refusal of prophylaxis has become more problematic.