Diagnosis and treatment of Guillain-Barré Syndrome in childhood and adolescence: An evidence- and consensus-based guideline.

This evidence- and consensus-based practical guideline for the diagnosis and treatment of Guillain-Barré Syndrome (GBS) in childhood and adolescence has been developed by a group of delegates from relevant specialist societies and organisations; it is the result of an initiative by the German-Speaking Society of Neuropediatrics (GNP), and is supported by the Association of Scientific Medical Societies (AWMF, Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften). A systematic analysis of the literature revealed that only a few adequately-controlled studies exist for this particular age group, while none carries a low risk of bias. For this reason, the diagnostic and therapeutic recommendations largely rely on findings in adult patients with GBS, for which there are a higher number of suitable studies available. Consensus was established using a written, multi-step Delphi process. A high level of consensus could be reached for the crucial steps in diagnosis and treatment. We recommend basing the diagnostic approach on the clinical criteria of GBS and deriving support from CSF and electrophysiological findings. Repetition of invasive procedures that yield ambiguous results is only recommended if the diagnosis cannot be ascertained from the other criteria. For severe or persistently-progressive GBS treatment with intravenous immunoglobulin (IVIG) is recommended, whereas in cases of IVIG intolerance or inefficacy we recommended treatment with plasmapheresis. Corticosteroids are ineffective for GBS but can be considered when acute onset chronic inflammatory demyelinating polyneuropathy (A-CIDP) is suspected due to a prolonged disease course. The full German version of the Guideline is available on the AWMF website (https://www.awmf.org/leitlinien/detail/ll/022-008.html).

Long-Term Respiratory Support for Children and Adolescents in Austria: A National Survey.

BACKGROUND: Population-based data on pediatric patients on long-term respiratory support (LTRS) in Austria are lacking. This study aimed to record the pediatric departments active in this field, as well as number and characteristics of patients on LTRS. METHODS: A national cross-sectional study was carried out by means of questionnaires sent to all pediatric departments in Austria. RESULTS: All departments answered to the questionnaires. On June 1st, 2013, the reference day for this study, 12 of the 41 pediatric departments in Austria were active in the field. At this time, these centers were caring for 143 patients, 111 (77.6%) of them under 18 years, which corresponds to a prevalence of 7.4 per 100 000. The patients suffered from neuromuscular disorders (44%), other neurological disorders (18.9%), disorders of respiratory drive (9.1%), obstructive sleep apnea (8.4%), thoracal and spinal diseases (8.4%), pulmonary disorders (4.9%) and other diseases (6.3%). Continuous positive airway pressure was used in 6.3%, non-invasive ventilation in 60.1% and invasive ventilation in 33.6% of the patients, respectively. LTRS was performed at home in 92.3%. CONCLUSION: LTRS represents a common management strategy in children and adolescents with a variety of disorders. Census reports such as this one provide the basis for appropriate planning of resource allocation. The age distribution of our patients shows the need for structured transition into adult care.

Long-term follow-up of pediatric patients treated with mitoxantrone for multiple sclerosis.

The chemotherapeutic agent mitoxantrone is approved for the treatment of aggressive multiple sclerosis (MS) in adults. Its use, however, is limited by the risk of severe adverse events including cardiotoxicity, myelosuppression, liver toxicity and secondary leukemia. The aim of this retrospective study is to present data on the safety, tolerability and efficacy of mitoxantrone in a small cohort of children with MS. 4 pediatric MS patients with a high relapse rate or severe, disabling relapses were treated with mitoxantrone and followed for 3.8-18 years. The cumulative dose of mitoxantrone was 36, 68, 84 and 120 mg/m (2), respectively. The frequency and severity of relapses as well as disability scores, decreased in the year after treatment onset. Short-term adverse events were transient in all cases. Cardiac monitoring by transthoracic echocardiography (TTE) showed asymptomatic left ventricular dysfunction during treatment in 1 patient, which was again normal at the next assessment. Long-term adverse events, including late-onset mitoxantrone-induced cardiotoxicity or secondary leukemia did not occur during the follow-up period. In our cohort of pediatric MS patients, mitoxantrone showed short-term reduction of disease activity and no long-term adverse events on follow-up. However, the risk of mitoxantrone-induced cardiotoxicity or toxic leukemia remains a life-long threat.

Two novel mutations in the GDAP1 and PRX genes in early onset Charcot-Marie-Tooth syndrome.

Autosomal recessive Charcot-Marie-Tooth syndrome (AR-CMT) is often characterised by an infantile disease onset and a severe phenotype. Mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene are thought to be a common cause of AR-CMT. Mutations in the periaxin (PRX) gene are rare. They are associated with severe demyelination of the peripheral nerves and sometimes lead to prominent sensory disturbances. To evaluate the frequency of GDAP1 and PRX mutations in early onset CMT, we examined seven AR-CMT families and 12 sporadic CMT patients, all presenting with progressive distal muscle weakness and wasting. In one family also prominent sensory abnormalities and sensory ataxia were apparent from early childhood. In three families we detected four GDAP1 mutations (L58LfsX4, R191X, L239F and P153L), one of which is novel and is predicted to cause a loss of protein function. In one additional family with prominent sensory abnormalities a novel homozygous PRX mutation was found (A700PfsX17). No mutations were identified in 12 sporadic cases. This study suggests that mutations in the GDAP1 gene are a common cause of early-onset AR-CMT. In patients with early-onset demyelinating AR-CMT and severe sensory loss PRX is one of the genes to be tested.

Isolated cytochrome c oxidase deficiency as a cause of MELAS.

BACKGROUND: MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) is one of the more common mitochondrial encephalomyopathies. About 80% of MELAS cases are caused by transition 3243A-->G in the mitochondrial tRNA(Leu(UUR)) gene (MT-TL1). Other mutations in MT-TL1, other mitochondrial tRNA genes and mitochondrial-encoded subunits of respiratory complex I account for the remainder of cases. OBJECTIVE: To characterise the molecular basis of a MELAS case without a mutation in any recognised MELAS target gene. RESULTS AND METHODS: Deletion of a single nucleotide (7630delT) within MT-CO2, the gene of subunit II of cytochrome c oxidase (COX), was identified by mitochondrial DNA (mtDNA) sequencing. The deletion-induced frameshift results in a stop codon close to the 5' end of the reading frame. The lack of subunit II (COII) precludes the assembly of COX and leads to the degradation of unassembled subunits, even those not directly affected by the mutation. Despite mitochondrial proliferation and transcriptional upregulation of nuclear and mtDNA-encoded COX genes (including MT-CO2), a severe COX deficiency was found with all investigations of the muscle biopsy (histochemistry, biochemistry, immunoblotting). CONCLUSIONS: The 7630delT mutation in MT-CO2 leads to a lack of COII with subsequent misassembly and degradation of respiratory complex IV despite transcriptional upregulation of its subunits. The causal association of the resulting isolated COX deficiency with MELAS is at odds with current concepts of the biochemical deficits underlying this common mitochondrial disease, and indicates that the genetic and pathobiochemical heterogeneity of MELAS is greater than previously appreciated.

The clinical spectrum of mitochondrial disease in 75 pediatric patients.

The clinical presentation of mitochondrial disorders in childhood is highly variable causing difficulties in diagnosis and management. We assessed records of 75 children (48 male, 27 female) with a biochemically and/or molecularly established mitochondrial disorder in a retrospective, multicentric study. The predominant biochemical defect was an isolated respiratory chain complex IV, followed by respiratory chain complex I, combined respiratory chain, and isolated pyruvate dehydrogenase complex (PDHC) deficiencies. For the 75 patients, the predominant clinical presentations were a nonspecific encephalomyopathy (n = 34) and Leigh syndrome (n = 17). Classical mitochondrial syndromes with associated mutations of the mitochondrial DNA were rare (n = 12). Eleven children had a lethal infantile mitochondrial disease (LIMD). This group comprised a considerable variety of clinical pictures, and the cohort was big enough to show the high frequency and wide spectrum of nonneuromuscular symptoms in mitochondrial disorders in childhood.

Magnetic resonance imaging in foetuses with bilateral moderate ventriculomegaly and suspected anomaly of the corpus callosum on ultrasound scan.

OBJECTIVE: The diagnosis of anomalies of the corpus callosum (ACC) in foetuses with bilateral moderate ventriculomegaly (BMV) is difficult by means of ultrasound scan. The aim of this study was to examine the value of the additional investigation with magnetic resonance imaging (MRI) in foetuses with BMV and suspected ACC on ultrasound scan. Pathogenesis and clinical presentation of BMV and ACC are discussed. METHODS: 41 foetuses with central nervous system (CNS) anomalies on ultrasound scan were assessed by ultrasonography and MRI from 1999 to 2001. Eight of these 41 foetuses presented with BMV and suspected ACC on ultrasound scan and were prospectively included in the study. Foetal investigations with sonography and MRI were analysed with regard to diagnostic confidence; results were correlated with post partum findings. Six of these 41 foetuses presented with BMV without suspected ACC on ultrasound scan and were retrospectively analysed. RESULTS: Ultrasonography suspected ACC in 8 foetuses with BMV. MRI confirmed the presence of ACC in 4 of these 8 cases. MRI additionally showed ACC in two of the six retrospectively analysed foetuses with BMV without suspected ACC on ultrasound scan. Prenatal MRI diagnosis was confirmed after delivery in all cases. CONCLUSION: MRI is more sensitive than ultrasonography in the evaluation of ACC in foetuses with BMV. For prenatal screening ultrasound still remains the investigation of choice.

Glatiramer acetate treatment in patients with childhood and juvenile onset multiple sclerosis.

BACKGROUND: Recent data indicate that in multiple sclerosis disease onset before the age of 16 is more common than previously assumed. However, current therapeutic options are limited to the treatment of acute attacks in these patients. Glatiramer acetate has been successfully applied in adults with relapsing-remitting multiple sclerosis, but there are no data available about the use of glatiramer acetate in childhood and juvenile onset multiple sclerosis. METHODS: Seven patients with relapsing-remitting multiple sclerosis and disease onset between 9 and 16 years of age were treated with daily subcutaneous injection of 20 mg glatiramer acetate (Copaxone). Patients were followed for 24 months. Treatment was initiated in all patients before the age of 18. RESULTS: The use of glatiramer acetate in our cohort of early onset multiple sclerosis patients was safe and well tolerated. Two out of seven patients remained relapse-free during the two year period. Clinical disability as measured by the EDSS remained stable in three out of seven patients. CONCLUSION: Due to the small number of patients the efficacy of the treatment has to be interpreted with caution. However, there might be a more pronounced treatment benefit in patients with low disability at treatment initiation and early treatment onset.

Degree of hypomyelination and magnetic resonance spectroscopy findings in patients with Pelizaeus Merzbacher phenotype.

As only 10 - 30 % of patients with a Pelizaeus Merzbacher disease (PMD) phenotype carry mutations of the proteolipid protein (PLP) gene, we were interested if the degree and time-dependent progression of abnormal MRI and MRS findings would discriminate patients with mutations of the PLP gene (Pelizaeus Merzbacher disease, PMD) from patients without a defect of the PLP gene (Pelizaeus Merzbacher-like disease, PMLD). For a standardised intraindividual follow-up and for comparison of the degree of hypomyelination, we have applied a newly developed semiquantitative myelination score on a total of 18 MRI series of 4 PMD and 4 PMLD patients. We found severe hypomyelination (< 50 % of normal) in 2 PMD and in 2 PMLD patients, moderate hypomyelination (< 75 % of normal) in 2 PMD and mild hypomyelination (> 75 % of normal) in 2 PMLD patients. Our score revealed a clear correlation between the degree of hypomyelination and the severity of clinical handicap in PMD but not in PMLD patients. MRS showed heterogeneous cerebral metabolite patterns in both patient groups and seems to reflect a mixture of unspecific changes due to primary hypomyelination and secondary gliosis and demyelination. Neither by MRI nor by MRS were patterns found that would allow differentiation between PMD and PMLD patients.

Auxological, ophthalmological, neurological and MRI findings in 25 Austrian patients with septo-optic dysplasia (SOD). Preliminary data.

UNLABELLED: Septo-optic dysplasia (SOD) comprises ophthalmological, endocrinological and neurological disorders resulting from varying degrees of midline malformation of the forebrain like visual impairment by optic nerve hypoplasia, endocrine deficits due to hypothalamic and/or pituitary anomalies, and psychomental retardation by associated cortical malformation. MRI shows aplasia/hypoplasia of the septum pellucidum and corpus callosum as a radiological hallmark. For etiology, genetic defects (Hesx1/HESX1 gene) as well as vascular disruption during embryonic brain development are discussed. AIM: To perform detailed analysis of morphological findings and clinical symptoms and to improve care of SOD patients by interdisciplinary management. PATIENTS: We investigated 25 patients with a mean age of 5.1 years at diagnosis. RESULTS: Pituitary insufficiency was present in 11/25 patients, multiple deficits in 6 of them. Bilateral optic nerve hypoplasia was found in 70% of patients, unilateral in 20%. Mild or moderate neurological disorders were observed in the majority of patients (14/20), EEG was usually normal (12/19). Analysis of MRI films revealed very heterogeneous morphological anomalies, ranging from isolated agenesis of the septum pellucidum to multiple malformations, involving the cortex. Malrotation of the hippocampal structures was a common finding. CONCLUSION: We conclude that only interdisciplinary management of SOD patients can ameliorate the exact diagnosis and outcome, depending on early visual or developmental support as well as early diagnosis and substitution of potentially life-threatening endocrine deficits.

Effects of oral creatine supplementation in a patient with MELAS phenotype and associated nephropathy.

An 18-year-old male patient with MELAS phenotype and 2 previous episodes of cerebral stroke, recurrent seizures and nephropathy, was treated with creatine monohydrate after the acute onset of psychomental regression and changing states of somnolence and aggressive and agitated behaviour. These symptoms disappeared completely after 4 weeks of treatment with creatine after which the patient regained all his previous mental abilites. Brain (white matter) proton magnetic resonance spectroscopy (chemical shift imaging) performed at 6 and 12 months of treatment showed lactic acid (Lac) accumulation and high creatine (Cr) levels in relation to choline-containing compounds (Cho). Urinary creatinine excretion as an indicator of the muscle and brain creatine pool increased upon short-term (12 days) high-dosage creatine supplementation (20 g per day) while plasma creatinine concentrations as possible indicators both of increasing creatine pool and of renal insufficiency increased during the course (28 months) of low-dosage creatine supplementation (5 g per day). Deterioration of renal function was finally indicated by urea retention and by impairment of renal creatinine clearance. These observations suggest that creatine supplementation may have a neuroprotective effect in patients with MELAS and episodes of acute mental deterioration. Adverse effects of creatine supplementation on renal function must be considered especially in patients with preexisting nephropathy.

[Opiate addiction in gravidity - consequences for the newborn. Results of an interdisciplinary treatment concept]. / Opiatabhängigkeit in der Schwangerschaft - Konsequenzen für das Neugeborene1 - Ergebnisse eines interdisziplinären Betreuungsmodells -

AIMS: To evaluate the outcome of infants of drug dependent mothers (IDM) after establishing an interdisciplinary attention concept at the University Hospital in Vienna. To compare the influence of different maintenance agents on neonatal morbidity. PATIENTS AND METHODS: All newborns of opiate dependent mothers were prospectively included from III 1995 to IX 1999. The following data were collected: maintenance agent (methadone, slow release morphine, buprenorphine), infectious status, demographic data, congenital malformations, perinatal complications, as well as incidence and duration of the neonatal abstinence syndrome (NAS). Medical treatment with phenobarbital (1995 - 96) or morphine hydrochloride (MoHCl) (1997 - 99), respectively, was indicated when Finnegan score exceeded 10. RESULTS: 88 neonates (38 females/50 males) with a median gestational age of 39 weeks were included, 18 (20.5 %) were born prematurely. The median birthweight was 2905 g, 24 (27.3 %) infants were small for date (< 10th percentile), 15 (17 %) microcephalic. The malformation incidence was 7.4 %. 63 (72 %) of all newborns had to be treated due to abstinence syndrome: in the methadone group 76 %, in the morphine group 93 %, but in the buprenorphine group 19 % only (p < 0.01). Median duration of withdrawal was 15.1 days (d) with significant difference after antenatal buprenorphine exposure compared to methadone and morphine exposure (8.3 d versus 15 d and 16.5 d respectively). In neonates treated with phenobarbital duration of NAS was 17.6 d, whereas NAS in infants with MoHCl therapy lasted 12.8 d (p < 0.05). CONCLUSION: Incidence and duration of NAS after buprenorphine exposure was significantly lower than after methadone and morphine exposure. Withdrawal time under morphin-hydrochloride therapy was reduced by one third compared to treatment with phenobarbital.

Long-term MRI observations of childhood-onset relapsing-remitting multiple sclerosis.

PURPOSE: Long-term MRI follow-up of childhood-onset relapsing-remitting multiple sclerosis (RRMS) was carried out in 4 cases. MRI findings were correlated with clinical course and characteristic differences from adult-onset RRMS were elaborated. METHODS: Two girls and one boy with true childhood-onset, and one girl with juvenile-onset RRMS underwent 5-16 MRI examinations within 6-8 years. The total number of lesions, the numbers of new, active, disappearing and reappearing lesions, infratentorial and U-fibre lesions, "giant" plaques and "black holes" were counted. Callosal atrophy and general brain atrophy were assessed. The findings were related to the physical status according to the Expanded Disability Status Scale (EDSS). RESULTS AND CONCLUSIONS: Results showed that the primary differences in childhood-onset RRMS compared to adult-onset RRMS lie in the lack of, or slower development of irreversible changes ("black hole" formation, brain atrophy). Despite callosal atrophy and intensive U-fibre region involvement, school performance was unchanged. Regarding the frequency of "giant" lesions, an even more pronounced white matter involvement was found in our children compared to adults. All children exhibited a rather "benign" disease course. A more intensive remyelination, less severe neuronal loss, and higher functional brain plasticity at younger ages may account for these differences.

Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome.

Subjects with Down syndrome exhibit various types of cognitive impairment. Neuropathological and neurochemical studies revealed similarities between Down syndrome and Alzheimer's disease, cholinergic deficits being the most consistent findings. To explore the potential for cognitive enhancement utilizing nicotinic stimulation, 8 patients with Down syndrome (aged 18.5-31 years) received placebo and a single dose of transdermal nicotine (5 mg patch) over 2h in a single-blind, within-subjects repeated measures design. Auditory event-related potentials (ERPs) and neuropsychological tests, comprising digit symbol performance subtest from WAIS-R and the Frankfurt Attention Inventory (FAIR) were performed. Effects of nicotine administration in Down syndrome individuals were a decrease of ERP-P3 latency in 7 of 8 subjects (electrode position Cz: 386.9+/-24.0 ms vs. 363.1+/-26.9.2 ms, placebo vs. nicotine, respectively; P = 0.058) and an increase of ERP-P3 amplitude in 6 of 8 subjects (electrode position Cz: 17.4+/-5.5 vs. 18.0+/-4.5 microV, placebo vs. nicotine respectively; P = 0.725). Neuropsychological tests exhibited improvements in digit symbol performance subtest in 4 of 8 subjects and 7 of 8 subjects in the Frankfurt Attention Inventory. These results suggest that stimulating central nicotinic receptors might have an acute cognitive benefit in young adult Down syndrome subjects.

Familial idiopathic West syndrome.

Two families, each with occurrence of West syndrome in two siblings, are presented. Monozygotic twins in family 1 developed infantile spasms at the age of 4 months. Two female siblings in family 2 started to have seizures at the age of 6 months, but 2 years apart. The family history; development prior to West syndrome; clinical, electroencephalographic, and neuroradiologic findings; diagnostic work-up; and treatment are described. The outcome in family 1 (follow-up after 2 years) showed no conspicuous findings on physical and neurologic examination, and psychomotor development appropriate to cognitive, motor, and language developmental age in both twins. In family 2 (follow-up after 3 and 5 years), the older sister only was one standard deviation below mean in intellectual developmental age. Simultaneous occurrence of infantile spasms in both siblings from these two families but with variable clinical expression suggests there is a genetic susceptibility and variable phenotypic expression. Long-term follow-up will demonstrate whether these cases may be classified as "familial idiopathic West syndrome."

Long term neurological and behavioral effects of graded perinatal asphyxia in the rat.

Perinatal hypoxic-ischemic states can cause irreversible damage to the brain, ranging from minimal brain dysfunction to death. Only few studies have been reported describing neurological, cognitive and behavioral deficits following perinatal asphyxia. We therefore decided to study long term effects of perinatal asphyxia in a well-documented animal model resembling the clinical situation. Caeserean section in rats was performed and the pups, still in the uterus horns, were placed into a water bath at 37 degrees C for periods of 5-20 min; pups were then given to surrogate mothers and examined at three month of age. Examinations consisted of a battery of motor and reflex tests, Morris water maze, multiple T-maze, elevated plus maze and open field studies. No abnormalities were found in rats even with long periods of perinatal asphyxia by neurological examination, in the open field and in mazes. Interestingly, in the elevated plus maze rats with long lasting exposure to hypoxia (15 and 20 min of asphyxia) showed reduced anxiety-related behavior. This finding may be relevant for the explanation of anxiety related disorders in adulthood with a tentative history in the perinatal period.

Effects of endotracheal suctioning in high-frequency oscillatory and conventionally ventilated low birth weight neonates on cerebral hemodynamics observed by near infrared spectroscopy (NIRS).

Adverse changes in cerebral hemodynamics during endotracheal suctioning have been reported in conventionally ventilated newborns, whereas observations on the effect of endotracheal suctioning during high-frequency ventilation have not been reported to date. The present study was designed to investigate the effect of endotracheal suctioning on cerebral hemodynamics in high-frequency and conventionally ventilated infants. Changes in cerebral concentration of oxygenated (cO(2)Hb) and deoxygenated hemoglobin (cHHb) and oxidized cytochrome aa3 (cCyt.aa3) were measured by noninvasive near-infrared spectroscopy. In an open prospective study, 26 suctioning periods in 9 high-frequency and in 6 conventionally ventilated newborn infants were investigated. Heart rate, arterial oxygen saturation (SaO(2)), mean blood pressure (MABP), and transcutaneous carbon dioxide tension (TcpCO(2)) were monitored continuously. In both groups, a marked decrease in heart rate, SaO(2) and in cO(2)Hb, an increase in cHHb, and a variable pattern in the concentration of total hemoglobin were noted during endotracheal suctioning. During suctioning, no statistically significant differences between the two methods of mechanical ventilation could be observed. We conclude that the mode of ventilation had no significant effect on changes in cerebral hemodynamics during endotracheal suctioning.

Latex sensitization in spina bifida appears disease-associated.

OBJECTIVE: The high prevalence of latex sensitization (up to 80%) in patients with spina bifida (SB) has been attributed to repeated exposure to latex products, whereas disease-associated factors have not been considered. METHODS: We compared children with SB (n = 21) and children with posthemorrhagic or congenital hydrocephalus (PH, n = 32), all of whom had a ventriculoperitoneal shunt since young age. Latex sensitization, number of operations, atopic history, and total IgE levels were evaluated. RESULTS: The following characteristics were recorded: age (SB: 52 months, range 1 to 264 months; PH: 71 months, range 1 to 192 months) and mean number of operations (SB: 2. 09; PH: 2.53). Of the SB group, 43% (9 of 21) showed elevated latex-specific IgE antibodies in contrast to 6% (2 of 32) in the PH group (P <.01). Latex-specific IgE antibodies were detected by 1 year of age, and one surgical operation was sufficient to induce latex-specific IgE-antibody production in patients with SB. CONCLUSIONS: The results suggest that the SB population bears a disease-associated propensity for latex sensitization. Sensitization to latex antigens may occur after the very first contact, arguing for latex avoidance measures from the very beginning of life.

Factor V Leiden and prothrombin gene G 20210 A variant in children with ischemic stroke.

OBJECTIVE: To investigate if the factor V Leiden mutation (F-V-LM) and/or the prothrombin gene G 20210 A variant (P-G20210A-V) are risk factors for acute stroke in Austrian children. PATIENTS: 33 children with acute ischemic stroke documented by computer tomography and/or magnetic resonance imaging of the brain were enrolled in an open multicenter survey. RESULTS: 6/33 children had F-V-LM (5 heterozygous, 1 homozygous). This represents 18% (95% CI: 6.7-39.9%) of our pediatric stroke population and thus exceeds the expected prevalence in the Austrian population of 4,6% (Fischer's exact test, p = 0.01). F-V-LM was not found in 11 children with neonatal stroke but in 6/22 children with stroke after the neonatal period. 5/6 children with F-V-LM had an underlying disorder that is a risk factor for stroke in children. The P-G20210A-V was detected in 1/26 (3.85%; 95% CI: 0.1-21.4%) patients. Comparison of the prevalence of P-G20210A-V in our study with that in the general population of Austria of 1% revealed no statistical significance (Fischer's exact test, p = 0.38). CONCLUSION: Our data suggest that the F-V-LM is a risk factor for acute stroke in Austrian children beyond the neonatal period. The P-G20210A-V apparently does not represent a risk factor for stroke in Austrian children.

Evidence against increased oxidative DNA-damage in Down syndrome.

In Down syndrome (DS), oxidative DNA-damage may play a role in the pathogenesis of characteristic mental retardation and precocious dementia of Alzheimer type. We measured the oxidized nucleoside, 8-hydroxy-2'-deoxyguanosine (8-OHdG), in nuclear DNA (nDNA) isolated from four different regions of cerebral cortex and cerebellum in 10 adult DS and 10 Alzheimer's disease (AD) patients compared to normal controls. Levels of 8-OHdG in post-mortem brain tissue were investigated by means of high-performance liquid chromatography with electrochemical detection. There was no significant increase in DS and AD compared to controls in any of the brain regions. Highest amounts of 8-OHdG were in temporal cortex in DS (180.0 +/- 9.6 nmol/g wet weight tissue), AD (172.4 +/- 14.6 nmol/g wet weight tissue) and controls (183.4 +/- 12.7 nmol/g). We conclude that the results provide evidence against an increased reactive oxygen species (ROS) induced damage to nDNA in DS and AD.