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.

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.

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.

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.

Intraventricular interferon and oral inosiplex in the treatment of subacute sclerosing panencephalitis.

We treated 22 patients with subacute sclerosing panencephalitis (SSPE) with intraventricular alpha-interferon (IFN) and inosiplex PO and followed them for 2 to 54 months. Three deaths occurred. Clinical improvement, demonstrated by decreasing scores on the Neurological Disability Index, occurred in 11/22 (50%); five patients became stable, and the progression rate of the disease decreased in three. The remission rate was significantly higher than untreated controls from the same institution. Patients who had a slowly progressive disease responded best to treatment. Serious side effects were rare. We recommend intraventricular IFN, combined with oral inosiplex, in the treatment of SSPE.

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.

Brain SPECT evaluation of patients with pure photosensitive epilepsy.

UNLABELLED: This study was performed to determine the utility of 99mTc-HMPAO brain SPECT in evaluating patients with pure photosensitive epilepsy. METHODS: Seven patients (2 boys, 5 girls), aged 8 to 15 yr (mean 11.1 +/- 2.5 yr), were studied. All patients underwent a detailed neurologic examination, interictal and ictal EEGs, CT and/or MRI and SPECT imaging. The baseline SPECT study was performed during the interictal period and the activation study was performed while the patients were having seizures provoked by watching television. RESULTS: The baseline SPECT study showed that six of seven patients had relatively hypoperfused regions in their frontal lobes that could involve the neighboring parietal and temporal regions. The activation study revealed that all seven patients had relative hyperperfusion in these brain regions that were relatively hypoperfused in the baseline study. The side-to-side asymmetry indexes for these visually-interpreted rCBF abnormalities ranged from 3% to 6%. CONCLUSION: The relatively consistent pattern of frontal rCBF alterations suggests that frontal lobe functions were implicated in the evolution of photosensitivity-related seizures in patients with pure photosensitive epilepsy.

D2 receptor imaging with iodine-123-iodobenzamide brain SPECT in infants with hypoxic-ischemic brain injury.

UNLABELLED: The purpose of this study was to evaluate the striatal dopamine D2 receptor density in infants with perinatal hypoxic-ischemic brain injury (HIBI) using 123I-iodobenzamide (IBZM) brain SPECT and to correlate the findings with the severity of HIBI and neurologic outcome. METHODS: Twenty infants who were diagnosed to have perinatal HIBI were included in this study. They were classified as having mild (n = 6), moderate (n = 10) or severe (n = 4) HIBI according to their neurologic findings at birth using the criteria of Sarnat and Sarnat. Neurologic outcome of these infants was determined by serial neurologic examinations and the Denver developmental screening test; 10 infants recovered without any deficit and the remaining 10 were affected to a degree varying from motor impairment to cerebral palsy. All 20 infants were examined using 123I-IBZM brain SPECT at age 7.8 +/- 2.3 mo. Transaxial slices were obtained 2 hr after intravenous injection of 300 micro ci (11.1 MBq) 123I-IBZM and the activity ratios of striatal to occipital cortex (ST/OC) were calculated. RESULTS: The mean ST/OC ratios in patients with mild, moderate and severe HIBI (1.219 +/- 0.078, 1.097 +/- 0.069 and 0.813 +/- 0.140, respectively) were significantly different from each other (p = 0.001). The infants who recovered from HIBI without any neurologic sequelae had higher mean ST/OC ratios than the others (1.184 +/- 0.010 versus 0.969 +/- 0.160, p = 0.002). CONCLUSION: The results of this study show that in infants with HIBI, striatal D2 receptor density decreases as the severity of injury increases. The D2 receptor density is higher in infants who recover without neurologic deficits compared to those who are affected neurologically. Dopamine D2 receptor imaging can be used to assess the severity of HIBI in children.

Cimetidine as an immunomodulator in subacute sclerosing panencephalitis: a double blind, placebo-controlled study.

Cimetidine, an H2 histamine receptor antagonist, was used in subacute sclerosing panencephalitis patients for its immunomodulatory effect. Patients were randomly assigned to cimetidine (n = 7) and placebo (n = 7) groups. Neurologic disability index, lymphocyte functions, cerebrospinal fluid measles antibodies and IgG index were evaluated before and after 2 months of treatment. The neurologic disability index of the cimetidine group remained stable during the study period whereas the placebo group worsened. There were no differences in the immunologic test results, cerebrospinal fluid measles antibody titers and IgG index of the two groups. This study suggests that cimetidine may have a favorable effect on the clinical progression of subacute sclerosing panencephalitis. Further studies are required to investigate its mechanism of action and the associated changes in immune status.

Biochemical alterations in neonatal hypoxic ischaemic brain damage.

Asphyxiated (n = 39) and control (n = 23) were elected for the study. Free radical-mediated lipid peroxidation, prostaglandin E2 and vitamin E levels were studied and the degree of hypoxic ischaemic encephalopathy was determined in each case. In the hypoxic group the concentration of prostaglandin E2 activity (P < 0.05) and malondialdehyde levels (P < 0.01) were significantly higher when compared to that of controls. The high vitamin E concentrations in the asphyxiated infants supports the role of oxygen free radicals in hypoxic ischaemic encephalopathy of newborns.

Nitric oxide in developing brain.

The role of NO in the neonatal brain, particularly during hypoxia and ischaemia has been studied extensively in animal models of focal and global ischaemia. The n-NOS and i-NOS activation have been found to be harmful whereas e-NOS activation has a neuroprotective effect in focal ischaemia (Fig. 1). The findings following global ischaemia are somewhat more controversial. Although all these studies clearly demonstrate that NO has an important role in the neonatal brain, it may be difficult to apply the results to humans for it is not clear when and which isoform of NOS gets activated following ischaemia in newborn infants. Also it is hard to determine the timing of intervention to inhibit or stimulate the production of NO in humans since we still do not know all the details about protective mechanisms of the human body. Some interventions may have a deleterious effect on some of those mechanisms. In addition, the relatively selective NOS inhibitors which are now used in animal experiments are not appropriate for human studies. New studies regarding the production of NO following ischaemia will be needed in newborns, together with the development of selective NOS inhibitors which can be used in humans. If the NO production follows the same pattern in humans as in animals at least the effects of i-NOS may be prevented either by selective inhibitors or by neuroprotective agents.

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.

The serum nitric oxide levels in patients with Duchenne muscular dystrophy.

Nitric oxide is formed in skeletal muscle by the neuronal type nitric oxide synthase and the signalling function of dystrophin and related compounds are in part mediated by nitric oxide. Duchenne muscular dystrophy, mdx mice and patients with Becker dystrophy demonstrated neuronal type nitric oxide synthase deficiency in muscle biopsy specimens. We have intended to find out whether the plasma nitric oxide levels show any abnormality in patients with Duchenne muscular dystrophy. Serum NO levels of Duchenne patients (4.191+/-2.82 micromol/l) were significantly lower than those of the control (39.53+/-19.43 micromol/l) and cerebral palsy (77.84+/-21.70 micromol/l) groups.

Tc-99m HMPAO brain perfusion imaging in young Down's syndrome patients.

Down's syndrome (DS) is characterized by moderate mental retardation and a variety of abnormalities involving multiple organ systems. There is a high incidence of Alzheimer's disease (AD) type dementia beyond the age of 35. In this study, single photon emission computed tomography (SPECT) brain perfusion imaging of young Down's syndrome patients was performed to define the perfusion pattern. Tc-99m HMPAO brain perfusion SPECT was performed on 17 young DS patients, aged 3-24 years (mean: 10.9+/-5.9 years). None of the patients had dementia symptoms. Brain perfusion scans were acquired 15 min after i.v. injection of 12 MBq/kg of Tc-99m HMPAO using a single head rotating gamma camera. Images were analyzed visually and semiquantitatively by defining side-to-side asymmetry index. Nine DS cases showed normal brain perfusion. Eight of the 17 cases revealed mostly unilateral parieto-temporal, parieto-occipital and frontal hypoperfusions. The side-to-side asymmetry indices for these visually interpreted regional brain perfusion abnormalities ranged from 6 to 15%. These findings revealing mostly unilateral parieto-temporal and frontal hypoperfusions may not be considered as predictive patterns of dementia related Alzheimer type perfusion deficits in DS. However, such findings may connect to other functional imaging studies related to the higher cortical dysfunction in mental retardation.

Selective involvement of the quadriceps muscle in congenital muscular dystrophies: an ultrasonographic study.

Muscle ultrasound scanning is a non-invasive and painless technique for evaluating muscle disorders in childhood. We have performed ultrasound scans of the quadriceps muscle in 26 children with various forms of congenital muscular dystrophies. There were 8 patients clearly showing selective involvement within the components of the quadriceps. In all cases showing selective involvement, the rectus femoris was spared and the vastus muscles were the affected group. Our findings support the concept of heterogeneity, often encountered in congenital muscular dystrophies.

Monomelic amyotrophy in siblings.

Monomelic amyotrophy is a rare, benign motor neuron disorder. Electrophysiologic studies are suggestive of localized chronic anterior horn cell disease. Two young siblings are reported with monomelic amyotrophy who had proximal muscle weakness confined to one arm. We propose that monomelic amyotrophy, at least in this family, is inherited as an autosomal recessive trait.

Tremor of tongue and dysarthria as the sole manifestation of Wilson's disease.

Neurological form of Wilson's disease in children usually manifests with dystonia as the initial sign. Tremor of extremities, dysarthria and ataxia may follow. Copper deposits in gray and white matter along with the basal ganglia. A pediatric case presenting with tremor of the tongue and dysarthria as the only findings of Wilson's disease is reported. Tongue tremor should also be taken into notice within the basal ganglia symptomatology.

Excitatory amino acids and taurine levels in cerebrospinal fluid of hypoxic ischemic encephalopathy in newborn.

The recent studies indicating the transiently enhanced expression of excitatory amino acid receptors in hypoxia vulnerable brain regions and the elevated concentration of aspartate and glutamate in cerebrospinal fluid of asphyxiated newborns strongly suggest the role of excitatory amino acids in hypoxic ischemic brain damage in the developing human brain. In this study, we compared the concentrations of glutamate, aspartate, taurine and glycine in the cerebrospinal fluid of asphyxiated infants with values of a healthy control group. The concentrations of aspartate (5.82 +/- 3.36), glutamate (1.76 +/- 1.0) and taurine (9.32 +/- 9.1) were significantly elevated in cerebrospinal fluid of asphyxiated infants (P < 0.05). When compared to the control group, the high levels of aspartate was correlated with the degrees of hypoxic-ischemic encephalopathy (HIE) and the varying outcome. The high levels of aspartate and glutamate in the asphyxiated patients adds further evidence to the role of excitotoxicity in hypoxic ischemic encephalopathy. The mental and motor development of the patients in asphyxiated group was followed for 3 years.