Confirmed primary HHV-6 infection in children with suspected encephalitis.

HHV-6 infection has been associated with neurological symptoms in children. Two variants of human herpes virus 6, HHV-6A and HHV-6B, have been identified. Their role in neurological infections is poorly understood. We studied 53 children with suspected encephalitis for HHV-6A (strain GS) and HHV-6B (strain Z29) antibodies using an indirect immunofluorescence test. Primary infection was separated from past infection by an IgG-avidity test. The identified primary infections were studied for HHV-6 specific DNA by PCR. Forty-one children of 53 had IgG antibodies to HHV-6. Six children had low avidity of HHV-6 IgG antibodies indicating acute primary infection; four to type A, one to B, and one to both types. By serology, HHV-6 viral etiology was suggested in 6/53 (11.3%) of cases. One of the six patients with primary infection had HHV-6 DNA in serum and two in CSF. The children with primary HHV-6 infection were significantly younger than the whole series, 2.3 years vs. 6.4 years. We conclude that primary HHV-6 infection appears to be an important associated or causative agent in neurological infections of young children, and it can be confirmed from a single serum specimen using the IgG-avidity test.

A major role of viruses in convulsive status epilepticus in children: a prospective study of 22 children.

UNLABELLED: A group of 22 previously healthy children with their first convulsive status epilepticus (SE), treated at Kuopio University Hospital, Finland, were prospectively studied. Eleven children had febrile and 11 afebrile SE. Polymerase chain reaction was used to detect specific DNA from CSF, enzyme immunoassays and immunofluorescence assays to detect specific antibodies in serum and CSF, viral cultures were obtained from CSF, throat and stool and antigen detection from throat specimens. Viral infection was identified in 10 of 11 children with febrile SE (91%) and in 7 of 11 with afebrile SE (64%). Human herpes virus 6 infection was identified in 12 children (55%), and in at least six of them the infection was primary. Single cases of human herpes virus 7, parainfluenza 3, adenovirus 1, echovirus 22, rota, influenza A and Mycoplasma pneumoniae infection were diagnosed. CONCLUSION: Viruses, human herpes virus 6 in particular, seem to be major associated factors in convulsive status epilepticus, both febrile and afebrile. Human herpes virus 7 and Mycoplasma pneumoniae are novel agents associated with status epilepticus.

Serum lipid concentrations and growth characteristics in 12-year-old children born small for gestational age.

According to Barker's hypothesis, children born small for gestational age (SGA) are at increased risk for cardiovascular diseases in adulthood. The aim of our study was to determine whether retarded fetal growth is associated with dyslipidemia in childhood and, if so, to find predictive factors in the growth characteristics of SGA children. We studied the serum lipid concentrations of 55 SGA children and their 55 appropriate for gestational age control subjects at the age of 12 y. Growth variables were recorded at birth, 5 y, and 12 y of age. The study group consisted of all full-term SGA children born at our university hospital during a 22-mo period in 1984-1986. Nearly half of the SGA children (47.3%) were in the highest quartile for serum total cholesterol of the appropriate for gestational age children (p = 0.038). In multiple logistic regression analysis, poor catch-up growth in height (odds ratio, 13. 8; 95% confidence interval, 2.0-97.5), female sex (odds ratio, 8.1; 95% confidence interval, 1.3-48.9), and early stage of puberty (odds ratio, 7.5; 95% confidence interval, 1.2-46.5) predicted high cholesterol level in the SGA children. By the age of 5 y, 20 (36.4%) SGA children showed catch-up growth of > or =2 SD scores in height, and 21 (38.2%) SGA children showed catch-up growth of > or =2 SD scores in weight from birth. At the age of 12 y, the SGA children were still significantly shorter (p<0.001) and lighter (p< 0.05) than the appropriate for gestational age children, even though their pubertal development was similarly advanced. In conclusion, to be born SGA has long-term consequences for later growth and may already influence the level of serum total cholesterol before the teens. SGA children with poor catch-up growth in height may be at the highest risk for hypercholesterolemia.

Persistent frontal P300 brain potential suggests abnormal processing of auditory information in distractible children.

The P300 event-related potential (ERP) was studied at the beginning, in the middle, and at the end of an auditory stimulus discrimination task in 70 normal 9-year-old children. Easily distractible children showed frontally a short-latency P300 response to target stimuli throughout the task, whereas in the non-distractible children the corresponding response was distinctly smaller and also showed a tendency to decrease in size towards the end of the task. The short-latency frontal P300 response reflects activation of the brain's orienting networks, and it normally decreases in size when stimuli lose their 'novelty value' with stimulus repetition. Persistent frontal P300 suggest that distractible children continued to show enhanced orienting to stimuli that should have already been well encoded and/or categorized.

Distractible children show abnormal orienting to non-attended auditory stimuli.

Event-related potentials were recorded in response to intermittently presented, non-attended trains of identical auditory stimuli in healthy 9-year-old children. In abnormally distractible children (n =24), the first tone in each train elicited a significantly larger N1 vertex response than in the non-distractible children (n 24), suggesting that increased distractibility may be associated with an abnormally strong cerebral orienting towards non-attended stimuli. A later negativity at around 300 ms, which increases in amplitude with stimulus repetition and may thus reflect the building up of a functional neuronal representation of the stimulus properties, was significantly smaller in the distractible than in the non-distractible children. These findings demonstrate that event-related potential measures may be useful in helping to understand the information processing found in distractible children.

Postdural puncture headache is not an age-related symptom in children: a prospective, open-randomized, parallel group study comparing a22-gauge Quincke with a 22-gauge Whitacre needle.

Many reports have shown a low incidence of postdural puncture headache (PDPH) and other complaints in young children. The objective of this open-randomized, prospective, parallel group study was to compare the use of a cutting point spinal needle (22-G Quincke) with a pencil point spinal needle (22-G Whitacre) in children. We studied the puncture characteristics, success rate and incidence of postpuncture complaints in 57 children, aged 8 months to 15 years, following 98 lumbar punctures (LP). The patient/parents completed a diary at 3 and 7 days after LP. The response rate was 97%. The incidence of PDPH was similar, 15% in the Quincke group and 9% in the Whitacre group (P=0.42). The risk of developing a PDPH was not dependent on the age (r < 0.00, P=0.67). Eight of the 11 PDPHs developed in children younger than 10 years, the youngest being 23-months-old.

P300 sequence effects differ between children and adults for auditory stimuli.

Variation of the P300 component was studied in normal children and adults during an auditory oddball paradigm. In children, the target stimuli that were preceded by a large number of standard stimuli elicited about twice as large P300 with a significantly shorter latency, a more widespread distribution, and an earlier positivity in the frontal area than those that were preceded by a small number of standard stimuli. The P300 variation was not as marked in adults as in children. Based on the context updating theory of the P300, the finding suggests that a long intertarget interval (ITI) results in a profound decay of the neural representation of the target stimulus in children; consequently, more resources are needed to update the neural representation, and the target may even be processed as a novel input. The P300 variation may provide information about the brain functions related to memory, attention, and orienting in children. This variation should be considered when assessing cognitive brain functions with event-related potentials in children.

Speech and language development of children born at < or = 32 weeks' gestation: a 5-year prospective follow-up study.

Speech and language comprehension and production were assessed at the age of 5 years in a cohort of children born preterm at < or = 32 weeks' gestational age (N=55) in comparison with children born at term and of similar age, sex, and social backgrounds. Data both including and excluding major neurological disabilities are presented. Mean performance for the entire group of preterm children was significantly lower than for the controls on most of the measures including the composite IQ scores. When the nine children who had major neurological disabilities were excluded from the preterm group, statistically significant differences were found on four of the total 12 speech and language measures. Intellectually normal preterm children without major neurological disability were slower than the controls on rapid word retrieval. In addition, difficulties in comprehending relative concepts were typical for the preterm children. The results suggest 'subtle dysnomia', which is indicative of later reading problems. On global verbal measures and on the basic speech and language aspects the study groups did not differ. Specific language impairment, defined as a discrepancy of > 1SD between Performance IQ and Verbal IQ scores, showed a tendency to be more common in the control group. Within both the study groups, the boys showed a tendency for a greater discrepancy between their Performance and Verbal IQ scores.

Spectrum of mutations in Finnish patients with Charcot-Marie-Tooth disease and related neuropathies.

Our patient material included families and sporadic patients of Finnish origin with the diagnosis of Charcot-Marie-Tooth (CMT) disease types 1 and 2, Dejerine-Sottas syndrome (DSS), and hereditary neuropathy with liability to pressure palsies (HNPP). We screened for mutations in the peripheral myelin protein genes connexin 32 (Cx32), myelin protein zero (P0) and peripheral myelin protein 22 (PMP22) by direct sequencing. All patients chosen for mutation screening were negative for the 1.5 Mb duplication/deletion at 17p11.2-p12. Eleven Cx32 mutations were found in 12 families, six with a CMT2 diagnosis, three with a CMT1 diagnosis and three with unclassified CMT. The total number of patients in these 12 CMTX families was 61, giving a minimum prevalence of 1.2/100,000 for CMTX in Finland. Four of the mutations, Pro58Arg, Pro172Leu, Asn175Asp and Leu204Phe, have not been previously reported. One male patient with an early onset CMT had a double Cx32 mutation, Arg22Gln and Val63Ile. The double de novo mutation was found to be of maternal grandpaternal origin. In the P0 gene a Ser78Leu mutation was found in one family with severe CMT1 and a de novo Tyr82Cys mutation was found in one DSS patient. Both mutations have been previously reported in other CMT1 families. A novel PMP22 mutation, deletion of Phe84, was found in one sporadic DSS patient. Our mutation screening results show the necessity of molecular diagnosis, in addition to clinical and electrophysiological evaluation, for proper subtyping of the disease and for accurate genetic counseling.

Neuropsychological analysis of the visuomotor problems in children born preterm at < or = 32 weeks of gestation: a 5-year prospective follow-up.

Forty-six intellectually normal children born preterm (< or =32 weeks of gestation) without major neurological disabilities and a control group of term children matched for age, sex, and parental educational and occupational status were assessed at the age of 5 years using neuropsychological tests emphasizing perceptual and visuomotor functions. The results show that in terms of cognitive functions these preterm children are a very heterogenous group, but many of them still have problems in visuospatial and sensorimotor functions. The preterm children achieved lower mean scores in tests where coordination and voluntary control of hands in combination with tactile, kinaesthetic, and visuospatial perception were needed. They had most difficulty with drawing directions of lines and in integrating two or more forms. They also had problems with 3-dimensional constructions as well as visual perception of rotated shapes or slopes of lines.

Epidemiology of encephalitis in children. A prospective multicentre study.

UNLABELLED: We found 175 cases with acute encephalitis in a population of 791,712 children aged 1 month-15 years during a 2-year surveillance period in 1993-1994. The overall incidence was 10.5/100,000 child-years with the highest figure in children < 1 year of age, 18.4/100,000 child-years. The microbial diagnosis was considered proven or suggested in 110 cases (63%); varicella zoster, respiratory and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes simplex and rota viruses comprised 5% each. A clearcut change seems to have occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus associated encephalitides have been almost eliminated. Varicella zoster, respiratory, and enteroviruses have increased in frequency and occur in younger age groups. New causes were identified, especially Chlamydia pneumoniae and HHV-6. Our data should assist in making a specific diagnosis and defining appropriate antimicrobial therapy. CONCLUSIONS: The spectrum of encephalitis in children has changed due to vaccination programs. The incidence, however, appears to be about the same due to increasing frequency of other associated old and new microbes.

Dual cerebral processing of elementary auditory input in children.

We compared event-related responses (ERPs) to non-attended frequent and intermittent auditory input in school-aged children and in young adults. In adults, both inputs elicited prominent auditory N100 responses at vertex. In children, intermittent stimulation evoked vertex responses with similar latency and refractoriness, whereas frequently delivered identical tones evoked responses on average at 240 ms. Sensitization of a separate neuronal population at 260-300 ms was obvious during intermittent stimulation in children. The dual behaviour, simultaneous 'habituation' of one neuronal population response and sensitization of another, may reflect the process of redirecting the attention and setting up a neuronal model. Furthermore, results suggest that a simplistic interpretation of developmental ERPs in which shortening of latencies represents maturation is insufficient.

Hearing loss at the age of 5 years of children born preterm--a matter of definition.

The effect of three common hearing impairment criteria on the prevalence of hearing loss was evaluated in 58 prospectively followed-up 5-year-old children born preterm at < or = 32 weeks of gestation. Audiological assessment was done as part of an extensive neurodevelopmental evaluation at the age of 5 years. With the criterion based on the classification of the World Health Organization (average threshold hearing level > 25 dB at frequencies of 0.5, 1 and 2 kHz, classified according to the less impaired side) there were two preterm children with mild hearing impairment. With Clark's criterion (unilateral average threshold hearing level > 15 dB at frequencies of 0.5, 1 and 2 kHz) eight children had slight hearing impairment; seven of these had conductive hearing problems. With the criterion of a single frequency-specific deficit > 15 dB for 0.25-4 kHz the number of hearing-impaired children was 28 out of 54 (51.9%), most of whom had conductive or unspecified hearing deficits. Moreover, of the four multiply handicapped, retarded children whose pure tone thresholds were not assessed monaurally, three would belong to the hearing-impaired group according to Clark's criterion and four according to the frequency-specific criterion.

Neurodevelopmental profile at five years of children born at < or = 32 weeks gestation.

Sixty children born preterm (gestational age < or = 32 weeks) and 60 control children matched by sex, and socio-economic and educational status of the parents were followed prospectively to the age of five years. Neurodevelopmental problems were surveyed by a detailed neurological and neuropsychological test battery, and by ophthalmological and hearing examinations. All except one of the preterm children with major disability had motor, visual-spatial and visual problems. The most frequent neurodevelopmental abnormalities encountered among preterm children without major disability were motor problems--emerging as gross and fine motor and/or visual-motor difficulties--and visual-spatial problems. Language difficulties were not associated with hearing problems. Among those without major disability, visual-spatial difficulties and ophthalmological problems seldom emerged simultaneously.

Ocular findings in prematurely born children at 5 years of age.

Fifty-eight prematurely born children (gestational age < or = 32 weeks) were studied at the age of 5 years. The ophthalmological examination was part of an extensive neurodevelopmental evaluation. The eye study revealed significant hyperopia (> or = + 2.0) in 22.4%, myopia (> or = -1.0 D) in 8.6%, astigmatism (> or = 1.0 D) in 12.1%, and anisometropia (> or = 1.0 D) in 12.1%. The myopic refractive error was high in all of the cases: from -6.0 to -14.0 D. Manifest strabismus was found in 24.2% and significant visual impairment or blindness in 6.9%. Optic atrophy and cicatricial retinopathy of prematurity were the main causes for severe visual defects. In the randomly selected full-term children of the same age, significant hyperopia was seen in 14.3%, astigmatism in 5.4% and strabismus in 1.8%. The pattern of the eye findings was different in the preterm children compared with those born at term.