Comparative heel stick study showed that newborn infants who had undergone repeated painful procedures showed increased short-term pain responses.

AIM: We evaluated the short-term effect of repeated pain exposure on the pain responses of newborn infants using different pain assessment methods, as this area had been under-researched. METHODS: We compared 20 term, large for gestational age infants and 40 term, appropriate for gestational age controls. All had undergone a heel stick for a newborn screening test just before discharge, but the larger babies had also undergone at least other five painful stimuli prior to that. A pulse oximeter and a skin conductance algesimeter (SCA) were connected to the babies during the heel prick, and video recordings were made. Crying time, the Neonatal Infant Pain Scale (NIPS), heart rate, peripheral oxygen saturation (SpO2 ) and SCA measurements were compared within and between the groups. RESULTS: After the heel prick, the crying time (p = 0.021) and NIPS (p = 0.013) scores were significantly higher in the study group and the SpO2 levels were significantly lower (p = 0.009), but the heart rate (p = 0.981) was not significantly different between the groups. SCA measurements did not differ significantly between the groups. CONCLUSION: Babies who received more painful stimuli during the first few days of life showed greater pain responses during a subsequent heel prick.

Long-term monitoring of a critically ill preterm infant with two-channel amplitude integrated electroencephalography.

Amplitude integrated electroencephalography (aEEG) is a user friendly technique suitable for long term continuous monitoring of cerebral electrical background activity. It is increasingly being used in monitoring high risk neonates in intensive care units. Newer two-channel aEEG monitors by providing data from both side of the brain may increase the sensitivity for detection of unilateral cerebral injury. Here we report a critically ill preterm neonate with intracranial hemorrhage who was monitored with the two-channel aEEG for 3 weeks continuously. Seizures were clearly detected by monitoring electroencephalographic activity of both hemispheres and efficacy of anticonvulsant therapy was evaluated objectively. Amplitude integrated EEG helps management of critically ill patients as it allows continuous long-term monitoring of brain functions.

Atypical presentations of subacute sclerosing panencephalitis in two neurologically handicapped cases.

Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disorder caused by persistent measles infection. Here, we report two neurologically handicapped cases presenting with atypical features of SSPE. Patient 1 who had mild mental retardation manifested acute encephalopathy with partial seizures and hemiplegia, mimicking encephalitis. He showed a fulminant course without myoclonia or a periodic electroencephalogram complex. Although SSPE is usually associated with an increased diffusion pattern, diffusion-weighted imaging of our patient showed decreased diffusion in the right hippocampus. Patient 2 with infantile hemiparesis presented with secondary generalized seizures, followed by asymettrical myoclonias involving the side contralateral to the hemiparesis. A periodic electroencephalogram complex was absent on the previously damaged brain regions. Our findings show that preexisting neurological disorders may modify the clinical or electrophysiological findings of SSPE, leading to atypical presentations. SSPE should be considered in the differential diagnosis of acute encephalopathy with lateralizing signs or unidentified seizures. Decreased diffusion resolution in diffusion-weighted-imaging may correlate with rapid clinical progression in SSPE.

Adjunctive lamotrigine for partial seizures in patients aged 1 to 24 months.

OBJECTIVE: This randomized, double-blind, placebo-controlled trial was conducted to assess the efficacy and tolerability of adjunctive lamotrigine for the treatment of partial seizures in infants aged 1 to 24 months. METHODS: The study used a responder-enriched design in which all patients received adjunctive lamotrigine during an open-label phase (n = 177; maximum maintenance dose 5.1 mg/kg/day for those on non-enzyme-inducing antiepileptic drugs [AEDs] or valproate and 15.6 mg/kg/day for those on enzyme-inducing AEDs). Patients meeting response criteria were randomly assigned to double-blind treatment for up to 8 weeks with continued lamotrigine (n = 19) or to withdrawal from lamotrigine (placebo; n = 19) while background AEDs were maintained. RESULTS: The proportion of treatment failures (patients who met escape criteria or withdrew before completing the double-blind phase) was lower with lamotrigine (58%) than with placebo (84%). This finding was not significant in the primary analysis (two-sided chi(2) test [primary endpoint]). A post hoc sensitivity analysis of the primary endpoint was also performed (p = 0.045 by one-sided, mid-p corrected Fisher exact test). The median time to meet escape criteria was longer with lamotrigine (42 days) than with placebo (22 days) (p = 0.059). During the last 28 days of the open-label phase, 53% of the patients had a >or=50% reduction in frequency of partial seizures with lamotrigine. Additional reduction in partial seizure frequency was observed during the double-blind phase compared with the last 4 weeks of the open-label phase among those randomly assigned to lamotrigine (32% with a >or=25% reduction) but not those randomly assigned to placebo (5% with a >or=25% reduction). Lamotrigine was well tolerated, with an adverse event profile comparable to that observed in older pediatric patients. CONCLUSION: Lamotrigine was well tolerated, and the data indicate that it may be efficacious in the treatment of partial seizures in infants aged 1 to 24 months.

A boy with small supernumerary marker chromosome X identified by FISH.

Marker or ring X chromosomes are frequently seen in Ullrich-Turner Syndrome with 46,X,r(X) karyotype, but only 8 children were reported with an extra marker X chromosome in at least some of their cell lines, we describe a 5 years old male patient who is mosaic (17%) for a cell line with an extra ring shaped marker X chromosome in addition to a normal 46,XY cell line. He had mild motor mental retardation, a dysmorphic face, dysplastic ears, high arched palate, cryptorchidism and brachydactyly. G-banding showed 46,XY[83]/47,XY,+r?[17] karyotype. NOR banding revealed no satellite region but its centromere was intact in C-banding. By fluorescent in situ hybridization (FISH) technique, dual X/Y alpha-satellite probes were used to detect the origin of ring shaped marker chromosome and 17% of his cells had two X chromosome signals due to marker X; hybridization with X chromosome inactivation center (XIST) specific probe revealed the absence of the locus on the ring chromosome. In this report, clinical features of our patient are compared with previously reported cases and the cytogenetic and molecular cytogenetic techniques used to detect origin of marker chromosome are discussed.

Brain perfusion assessed by 99mTc-ECD SPECT imaging in pediatric patients with neurally mediated reflex syncope.

BACKGROUND: The involvement of cardiogenic and neurogenic mechanisms in neurally mediated reflex syncope is well documented. In our previous studies in patients with neurally mediated reflex syncope, we have found evidence for differential regulation of the noradrenergic receptors in tilt-positive and tilt-negative patients. The present work concentrates on the observations of differences in regional brain perfusion using brain SPECT via injecting the patient at the completion of the tilt test. METHODS AND RESULTS: The following study was designed to assess the reduction and regional differences in cerebral blood flow by means of SPECT using technetium-99m labeled V-oxo-1,2-N1ethylenedylbisl-cysteine diethylester (ECD) in patients with an injection during tilt testing. Twenty patients with NMS were included in the study with a mean age of 12.2 years (age range; 8-16 years). HUT was positive in 10 patients and negative in 10 patients. When tilt (+) and tilt (-) were evaluated together, regional cortical/cerebellum ratios were ranging from 0.85 to 1.25 in different cortical areas with highest variability of perfusion index in left frontoparietal cortex. The lowest perfusion index values were observed in the left anterior frontal region followed by the left prefrontal-frontoparietal-anterior, parietal-orbito frontal, and anterior temporal regions where perfusion is predominantly supplied via the anterior and middle cerebral arteries, while these differences did not reach statistical significance in a single dominant region compared to the other regions examined using ANOVA (P > 0.05) with this sample size. Decreases in [99mTc]ECD uptake were more widespread regionally on the left hemisphere than were decreases in right side of the brain. However when tilt- and tilt+ groups were compared, perfusion was significantly lower in the right periinsular posterior parietal and temporal regions (P < 0.05) in tilt + group. CONCLUSION: These tilt induced regional differences in brain perfusion suggest the distinct roles of middle cerebral artery dominant territory-related vasodepressor compensation mechanisms in neurally mediated reflex syncope phenomena where cerebral lateralization of cardiac control and insular ischemia may play an important role.

Macular retinitis as a first sign of subacute sclerosing panencephalitis: the importance of early diagnosis.

PURPOSE: Subacute sclerosing panencephalitis (SSPE) is a subacute inflammatory and neurodegenerative encephalitis related to the measles (rubeola) virus and usually affecting children and young adults. The overwhelming majority of cases follow a progressive downhill course leading to death, although there have been a few case reports of patients who have apparently gone into remission. Ocular changes occur in up to 50% of SSPE cases. Visual complaints, if present, generally antedate the onset of neurological symptoms by a few weeks or months. Here, we report two cases of SSPE presenting with ocular findings and their prognoses. METHODS: Case reports. In the first case, a 17-year-old male presenting with macular retinitis, the macular findings were mistaken for a heredodegenerative disorder and diagnosis was postponed until neurological findings took place. He died six months after the appearance of his first ophthalmic symptoms despite intravenous immune globulin and isoprinosine therapy. The second case was a 14-year-old male, who presented with only ophthalmological complaints. His diagnosis was based on both ophthalmological findings and high doses of measles IgG in the cerebrospinal fluid (CSF); isoprinosine and intramuscular beta-interferon therapy was started before the onset of neurological findings and in the follow-up time of about 18 months, neurological findings consistent with SSPE did not develop. RESULTS: The characteristic finding of macular retinitis in SSPE patients is rapid recovery in about one month without therapy. After improvement, neurological findings take place. Once suspected, the diagnosis of SSPE is easily established by the demonstration of high levels of measles antibody in the serum and CSF. Early diagnosis can be made with typical ocular findings and high IgG titers for rubeola in CSF. CONCLUSION: We suppose that ophthalmic manifestations, especially macular retinitis, may be useful in the diagnosis and management of SSPE cases with elevated IgG titers for rubeola in CSF. The typical clinical findings must be familiar to every ophthalmologist so that diagnostic pitfalls can be prevented and early therapy started. It may be discussed if early diagnosis and therapy will be possible before neurological signs appear, the prognosis of this relentless disease may show a more favorable course.

Serum carnitine levels in newborns with perinatal asphyxia and relation to neurologic prognosis.

Neonatal hypoxic encephalopathy is one of the major causes of permanent neurological sequel. This study was conducted to investigate serum total, free and acylcarnitine levels in asphyxiated newborns with or without encephalopathy. Serum total, free and acylcarnitine levels were investigated in 21 newborns with and seven asphyxiated newborns without signs of encephalopathy. The newborns with encephalopathy were further divided into grade 1, 2 and 3 encephalopathy groups. Serum total and acylcarnitine concentrations of the whole encephalopathy group were significantly lower than the non-encephalopathy group (p = 0.042 for both). Serum total and acylcarnitine concentrations of grade 3 encephalopathy group were significantly lower than the non-encephalopathy group (p = 0.014 and p = 0.040, respectively). No significant differences were noticed for free carnitine levels. Total carnitine levels were positively correlated with birth weight and 10th minute apgar score, whereas acylcarnitine levels were found to correlate with cord blood pH and free carnitine levels with birth weight. Cord blood pH, and total carnitine levels were found to be the most significant determinants of the neurological outcome at one year of age. It was emphasized that carnitine deficiency could occur in severely affected asphyxiated newborns and it is related to the outcome at one year of age.

Exon deletions in the GCHI gene in two of four Turkish families with dopa-responsive dystonia.

Most cases of dopa-responsive dystonia (DRD) are thought to be caused by mutations in the GCHI gene; however, by sequencing, mutations are found in only 40% to 60%. Recently, a single report identified, via Southern blot analysis, a large genomic GCHI deletion in a "mutation-negative" case. This report describes four families with DRD, two of which carry large deletions, thus confirming that deletions are an important subtype of GCHI mutations. These deletions were detected by quantitative duplex PCR that is amenable to DNA diagnostics.

Is increased D2 receptor availability associated with response to stimulant medication in ADHD.

The purpose of this study was to estimate striatal dopamine (D2) receptor availability in non-drug treated children with attention-deficit-hyperactivity disorder (ADHD) before and after methylphenidate therapy, and to examine correlations between severity of symptoms and response rates to stimulant medication with levels of striatal D2 receptor binding. Nine children (six males, three females; mean age 9.8 years, SD 2.3 years) with ADHD participated. All underwent iodobenzamide (123I IBZM) brain SPECT within 2 hours following intravenous injection of 123I IBZM before and 3 months after methylphenidate therapy. A semiquantitative approach was used to generate indices of specific D2 receptor binding in the basal ganglia. Specific binding ratios at baseline were higher than the previously reported specific binding values obtained in studies using young healthy adults. D2 availability reduced significantly (paired t-test,p<0.05) as a function of methylphenidate therapy in patients with ADHD in all four regions of the striatum. When the relation between therapy response and D2 availability was investigated, we observed that the higher the baseline D2 levels were, the higher the response rate was (detected as the percentage reduction of hyperactivity scores and Conners Teacher Rating Scale scores), while no such trend was observed between the initial D2 binding levels and the response in attention-deficit scores. Results indicate that in non-drug treated children with ADHD, higher D2 receptor availability is observed at baseline which is down-regulated back to reported near-normal values after methylphenidate therapy. The effect of methylphenidate on D2 receptor levels in patients with ADHD is similar to that observed in healthy adults; a down-regulation phenomenon within 0 to 30%. In addition, initially higher values of D2 availability seem to indicate better response to methylphenidate therapy in ADHD.

The impact of pre- and perinatal factors on attention-deficit and disruptive behavior disorders.

Diagnosis of attention-deficit and disruptive behavior disorders defines a group of disorders which have common properties. This group consists of attention-deficit hyperactivity disorder, conduct disorder and oppositional defiant disorder. In order to differentiate these disorders, which share similar properties, it is important to verify the existing differences. In this respect, differences between and distribution of perinatal factors in these three disorders were investigated. The study was conducted in the Child Psychiatry and Pediatric Neurology Departments over a 20-month period. Two hundred and seventy children out of 1,556 attendant with various complaints were diagnosed to have one of the following disorders: 121 had attention-deficit hyperactivity disorder, 50 had oppositional defiant disorder and 99 had conduct disorder. The prenatal and perinatal data of the patients were evaluated retrospectively by a neonatologist. With regard to the investigated parameters, none showed any significant difference between the three groups when compared. The three disorders, which share many similarities in terms of the symptoms, also show similarities in terms of perinatal factors. Since we did not find any study similar in design, our results, although statistically not significant, are discussed in light of the little data available.

Complex partial seizure mimicking psychotic reaction in an adolescent.

A previously healthy 15-year-old boy initially diagnosed to have acute psychotic reaction had a history of a single generalized seizure and prolonged amnestic states of varying intensity and duration. An ictal electroencephalogram (EEG) showed bitemporal ictal discharges starting from the left side. Carbamazepine was started. A magnetic resonance imaging (MRI) obtained on the 10th day of the antiepileptic therapy showed increased signal intensity on the T2 weighted images. The patient's memory function markedly improved during 10 months' follow-up with antiepileptic treatment, although he described brief attacks of dizziness. A repeat MRI examination showed normal findings. The amnesticstates were thought to be due to frequent complex partial seizures, and transient MRI changes to hippocampal edema. This case illustrates the importance of epileptic disorders in the differential diagnosis of psychiatric conditions.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay in two unrelated Turkish families.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay is an early onset form of hereditary spastic paraplegia with a peculiar clinical presentation. In addition to cerebellar findings which manifest first with ataxic gait in early life and spasticity, on an evolutionary basis, there is axonal neuropathy, prominent myelinated fibers in the optic fundus, and evidence of cerebellar atrophy that can be detected by cranial MRI. Intelligence is usually normal, however lower IQs have also been documented. This disorder mainly originates from the Charlevoix-Saguenay region of Quebec. Here, we report two Turkish families linked to the disease locus on chromosome 13 q12. There was homozygosity and segregation of disease haplotypes in both families. This form of spastic ataxia may be more common than originally presumed.

Why hypothermia in neonatal hypoxic ischemic encephalopathy?

The incidence of asphyxiated full-term infants is still high in both high income and developing countries. In up to 80 percent of infants, moderate to severe birth asphyxia results in long-term neurological sequelae. Many years of experimental work and a limited data on hypoxic-ischemic neonates have supported the hypothesis that hypothermia after the primary insult induces permanent neuroprotection. In this mini overview, we attempt to update pediatricians in this aspect and raise the following: Will the future treatment include hypothermia along with the conventional and or other promising drugs affecting different aspects of the hypoxia-ischemia?

An apparently dominant bipolar affective disorder (BPAD) locus on chromosome 20p11.2-q11.2 in a large Turkish pedigree.

Bipolar affective disorder (BPAD), also known as manic-depressive illness, is a common complex, polygenic disorder characterised by recurrent cyclic episodes of mania and depression. Family, twin, and adoption studies strongly suggest a genetic predisposition/susceptibility to BPAD, but no genes have yet been identified. We studied a large Turkish pedigree, with an apparently autosomal dominant BPAD, which contained 13 affected individuals. The age of onset ranged from 15-40 with a mean of 25 years. The phenotypes consisted of recurrent manic and major depressive episodes, including suicidal attempts; there was usually full remission with lithium treatment. A genome-wide linkage analysis using a dominant mode of inheritance showed strong evidence for a BPAD susceptibility locus on chromosome 20p11.2-q11.2. The highest 2-point lod score of 4.34 at theta = 0 was obtained with markers D20S604, D20S470, D20S836 and D20S838 using a dominant model with full penetrance. Haplotype analysis enabled the mapping of the BPAD locus in this family between markers D20S186 and D20S109, to a region of approximately 42 cM.

Evaluation of dysrhythmia in children with muscular dystrophy.

Myocardial involvement and dysrhythmia are common findings with muscular dystrophy and are among the leading causes of death. The authors evaluated rhythm and conduction abnormalities in children with muscular dystrophy by electrocardiography, signal-averaged electrocardiography, and Holter monitoring. Twenty-nine patients (mean age, 8 years) and 29 healthy control subjects were included in the study. Sixty-two percent of patients had electrocardiographic abnormalities defined as deep Q waves in V6, tall R waves in V1, and QRS axis deviation. The cardiomyopathy index was significantly greater in the patient group whereas QT and QTc dispersion values showed no significant difference. Holter monitoring revealed premature atrial and ventricular contractions more frequently than normal. However all were classified as Lown I and II. Mean heart rate was significantly higher in the patient group. The electrocardiograms of 41% of the patients showed late potentials. No relationship with these changes and cardiac function was observed. During the study, one patient died whose cardiomyopathy index was longer and had late potentials detected with signal-averaged electrocardiography. In conclusion, standard electrocardiography, cardiomyopathy index, signal-averaged electrocardiography, and Holter monitoring are valuable and reliable monitoring methods in children with muscular dystrophy.

Moyamoya syndrome after radiation therapy for optic pathway glioma: case report.

We present a 4-year-old girl with neurofibromatosis-1 who developed moyamoya syndrome characterized by bilateral stenosis or occlusion of the distal internal carotid arteries and their branches, leading to the development of an abnormal vascular network. In light of a literature review, the postradiation vasculopathy of the moyamoya type and its relationship with neurofibromatosis-1 are discussed.

Tremor and myoclonus heralding Hashimoto's encephalopathy.

We report the clinical laboratory, electroencephalography (EEG), magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) findings in a 15 year-old euthyroid girl with autoimmune thyroiditis and encephalopathy. She had stupor, coma and generalized tonic clonic seizure preceded by tremor and myoclonus with a previous misdiagnosis of epilepsy and encephalitis. Response to steroid after the 3rd relapse was excellent. Another four children in the literature are also discussed.

Evaluation of bone mineral metabolism in children receiving carbamazepine and valproic acid.

Dual energy X-ray absorptiometry (DXA) was used to assess lumbar spine (L2-4) and femoral neck bone mineral density (BMD) in 36 children taking either carbamazepine or valproic acid for longer than one year, for generalized idiopathic epilepsy. Patients were matched with controls. Biochemical parameters of bone mineral metabolism were also measured. BMD values at both the femur neck and lumbar spine in both the carbamazepine and valproic acid groups were not significantly different from that of the control group. Serum levels of calcium were subnormal and alkaline phosphatase levels were high in the carbamazepine group. Urinary calcium levels were significantly lower in both groups than in the control group (p< or =0.05) and also significantly lower in the valproic acid group than in the carbamazepine group (p< or = 0.05). There were no other significant biochemical changes in either group. In conclusion, the results suggest that valproic acid and carbamazepine monotherapies have minimal effects on bone mineral metabolism, but routine monitoring of risk and consideration of prophylactic vitamin D supplementation is important.