26 research outputs found
The prevalence and clinical relevance of hyperhomocysteinemia suggesting vitamin B12 deficiency in presumed healthy infants
Background
Previous studies have demonstrated a high prevalence of biochemical vitamin B12 deficiency in infants in Norway. Increased total homocysteine (tHcy) is the most important marker of B12 deficiency in infants. There is a need to evaluate its clinical relevance.
Aims
To investigate the prevalence of hyperhomocysteinemia (S-tHcy > 8 μmol/L) suggestive of suboptimal B12 status and the prevalence of clinically relevant hyperhomocysteinemia in presumed healthy infants in Norway. Further, to evaluate risk factors, presence of symptoms and psychomotor development in these children.
Methods
In a prospective study we clinically examined 252 infants aged 3–7 months using standardized neurological and psychomotor tests prior to analyzing biochemical B12 deficiency markers in 250 infants.
Results
Twenty-five of 250 (10%) infants had hyperhomocysteinemia combined with clinically relevant symptoms suggestive of B12 deficiency. Hyperhomocysteinemia was associated with tremor, excessive sleep, and sub-normal scores in the fine motor section of the Ages and Stages Questionnaire. One-hundred and fourteen of 250 (46%) infants had hyperhomocysteinemia. Multiple regression analysis showed months of infant formula use as the strongest negative predictor for hyperhomocysteinemia.
Conclusion
We have demonstrated associations between symptoms suggestive of infant B12 deficiency and increased levels of tHcy in presumed healthy infants The combination of hyperhomocysteinemia and associated relevant symptoms suggestive of B12 deficiency was a common finding, albeit most infants with hyperhomocysteinemia did not show symptoms.publishedVersio
Incidence rates of progressive childhood encephalopathy in Oslo, Norway: a population based study
<p>Abstract</p> <p>Background</p> <p>Progressive encephalopathy (PE) in children is a heterogeneous group of diseases mainly composed of metabolic diseases, but it consists also of neurodegenerative disorders where neither metabolic nor other causes are found. We wanted to estimate the incidence rate and aetiology of PE, as well as the age of onset of the disease.</p> <p>Methods</p> <p>We included PE cases born between 1985 and 2003, living in Oslo, and registered the number presenting annually between 1985 and 2004. Person-years at risk between 0 and 15 years were based on the number of live births during the observation period which was divided into four 5-year intervals. We calculated incidence rates according to age at onset which was classified as neonatal (0–4 weeks), infantile (1–12 months), late infantile (1–5 years), and juvenile (6–12 years).</p> <p>Results</p> <p>We found 84 PE cases representing 28 diagnoses among 1,305,997 person years, giving an incidence rate of 6.43 per 100,000 person years. The age-specific incidence rates per 100,000 were: 79.89 (<1 year), 8.64 (1–2 years), 1.90 (2–5 years), and 0.65 (>5 years). 66% (55/84) of the cases were metabolic, 32% (27/54) were neurodegenerative, and 2% (2/84) had HIV encephalopathy. 71% (60/84) of the cases presented at < 1 year, 24% (20/84) were late infantile presentations, and 5% (4/84) were juvenile presentations. Neonatal onset was more common in the metabolic (46%) (25/55) compared to the neurodegenerative group (7%) (2/27). 20% (17/84) of all cases were classified as unspecified neurodegenerative disease.</p> <p>Conclusion</p> <p>The overall incidence rate of PE was 6.43 per 100,000 person years. There was a strong reduction in incidence rates with increasing age. Two-thirds of the cases were metabolic, of which almost half presented in the neonatal period.</p
Hippocampal volumes are important predictors for memory function in elderly women
<p>Abstract</p> <p>Background</p> <p>Normal aging involves a decline in cognitive function that has been shown to correlate with volumetric change in the hippocampus, and with genetic variability in the APOE-gene. In the present study we utilize 3D MR imaging, genetic analysis and assessment of verbal memory function to investigate relationships between these factors in a sample of 170 healthy volunteers (age range 46–77 years).</p> <p>Methods</p> <p>Brain morphometric analysis was performed with the automated segmentation work-flow implemented in FreeSurfer. Genetic analysis of the APOE genotype was determined with polymerase chain reaction (PCR) on DNA from whole-blood. All individuals were subjected to extensive neuropsychological testing, including the California Verbal Learning Test-II (CVLT). To obtain robust and easily interpretable relationships between explanatory variables and verbal memory function we applied the recent method of conditional inference trees in addition to scatterplot matrices and simple pairwise linear least-squares regression analysis.</p> <p>Results</p> <p>APOE genotype had no significant impact on the CVLT results (scores on long delay free recall, CVLT-LD) or the ICV-normalized hippocampal volumes. Hippocampal volumes were found to decrease with age and a right-larger-than-left hippocampal asymmetry was also found. These findings are in accordance with previous studies. CVLT-LD score was shown to correlate with hippocampal volume. Multivariate conditional inference analysis showed that gender and left hippocampal volume largely dominated predictive values for CVLT-LD scores in our sample. Left hippocampal volume dominated predictive values for females but not for males. APOE genotype did not alter the model significantly, and age was only partly influencing the results.</p> <p>Conclusion</p> <p>Gender and left hippocampal volumes are main predictors for verbal memory function in normal aging. APOE genotype did not affect the results in any part of our analysis.</p
Narcolepsy type 1 patients have lower levels of effector memory CD4<sup>+</sup> T cells compared to their siblings when controlling for H1N1-(Pandemrix™)-vaccination and HLA DQB1∗06:02 status
Study objectives
Evidence suggests a cell-mediated autoimmune pathogenesis for narcolepsy type 1 (NT1), but it is not clear whether the disease is associated with overall changes in T cell subsets. The increase in NT1 incidence after H1N1 vaccination campaign with the Pandemrixâ„¢ vaccine suggests that disease-relevant changes in the immune system following this vaccination were important. In this study, we aimed to investigate differentiated T cell subsets and levels of CD25 and CD69 activation markers in a cohort of mainly Pandemrixâ„¢-vaccinated NT1 patients compared with their vaccinated and unvaccinated siblings.
Methods
Peripheral blood mononuclear cells were collected in parallel and analysed with flow cytometry in 31 NT1 patients with disease onset after the 2009 influenza A (H1N1) pandemic and/or Pandemrixâ„¢ vaccination and 45 of their non-narcoleptic siblings (29/31 and 34/45 vaccinated, respectively).
Results
We observed significantly lower effector memory CD4+ T cell levels in NT1 patients compared to their siblings, when controlling for HLA DQB1∗06:02 and vaccination status. Further, within the sibling group, vaccination status significantly affected frequencies of central memory and CD8+CD25+ T cells, and HLA DQB1∗06:02 status significantly affected frequencies of CD4+CD25+ T cells.
Conclusion
We confirm that NT1 is associated with lower levels of effector memory CD4+ T cells in peripheral blood. Importantly, this finding was only significant when controlling for vaccination and HLA status in both patients and controls. We thus demonstrate the importance of characterizing such factors (eg HLA and vaccination) when studying T cell subsets in NT1. This might explain earlier conflicting results
Head and neck paragangliomas in Norway, importance of genetics, updated diagnostic workup and treatment
Background
Head and neck paragangliomas (HNPG) are rare and predominantly benign tumours, originating from the neuroendocrine paraganglionic system. A considerable proportion of HNPGs are hereditary, depending on the population.
Aims/objectives
The purpose of this study was to estimate the rate of hereditary HNPGs in a Scandinavian (Norwegian) population, report long-term experience with HNPGs and offer all patients diagnosed an updated follow-up, with emphasis on identifying hereditary HNPGs through genetic screening and multifocality by 18 F-2-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).
Material and methods
Our study was a partly retrospective and partly prospective cohort study. It included patients with HNPG diagnosed at Oslo University Hospital (OUH), Rikshospitalet between 1990 and 2017. The patients underwent genetic testing, 18F-FDG PET/CT and measurement of catecholamines and meta-nephrines in the plasma. All resection specimens and biopsies were subjected to histopathological review. The genetic testing protocol consisted of testing for mutations in the following genes; SDHD, SDHB, SDHC, VHL and RET.
Results
Sixty-three patients were included in the study with a median age of 49 years (range 12 − 80). Cranial nerve dysfunction was present upon diagnosis in 13%, and 14% had multifocal paraganglioma (PG) disease. Fifty-six patients (89% of all the patients) underwent genetic testing, and 29% of these had a PG related mutation. Seven of the eight patients (88%) with multifocal PGs who underwent genetic testing had a mutation. In two of the patients, the 18F-FDG PET/CT revealed unknown and subclinical multifocality.
Conclusions and significance
This is the first study with systematic genetic workup and PET/CT imaging in Scandinavia of HNPG patients. The mutation rate was within the lower range reported in the literature with respect to HNPGs. Combining genetic testing and PET/CT imaging in the diagnostic workup of HNPGs is valuable
Breastfed Infants With Spells, Tremor, or Irritability: Rule Out Vitamin B12 Deficiency
Background
In Norway, 5-10% of neonates and infants have biomarkers suggesting vitamin B12 deficiency from newborn screening tests and unselected clinical screening, respectively.
Aims
The aims were to identify risk factors and describe presenting symptoms and biochemical profiles in infants diagnosed with vitamin B12 deficiency.
Methods
In this case-control study, we searched hospital medical records for infants younger than one year born in 2011-2018, diagnosed with vitamin B12 deficiency. We compared 85 cases with a control group of 252 infants aged 3-7 months. Parents completed questionnaires.
Results
Of the 85 cases with vitamin B12 deficiency, 80% presented with spells (37%) of apneas, motor seizures, or absences within the first two months of life. Tremor (29%) and irritability (18%) were the most common findings at the first examination. Serum total homocysteine ≥10 μmol/L was found in 77% of cases compared to 28% of controls (P < 0.001). None of the mothers were vegetarians, but 25% reported a previous history of vitamin B12 deficiency and 7% had celiac disease. The dose of nitrous oxide given during labor was significantly associated with infant serum total homocysteine level at diagnosis (r = 0.37, 95% confidence interval = 0.16-0.55, P < 0.001) for cases, but not for controls.
Conclusion
Spells, tremor, and irritability are common findings in early infant vitamin B12 deficiency. Nitrous oxide given during labor is proposed as a contributing risk factor to the development of early infant vitamin B12 deficiency
Breastfed Infants With Spells, Tremor, or Irritability: Rule Out Vitamin B12 Deficiency
Background: In Norway, 5-10% of neonates and infants have biomarkers suggesting vitamin B12 deficiency from newborn screening tests and unselected clinical screening, respectively.
Aims: The aims were to identify risk factors and describe presenting symptoms and biochemical profiles in infants diagnosed with vitamin B12 deficiency.
Methods: In this case-control study, we searched hospital medical records for infants younger than one year born in 2011-2018, diagnosed with vitamin B12 deficiency. We compared 85 cases with a control group of 252 infants aged 3-7 months. Parents completed questionnaires.
Results: Of the 85 cases with vitamin B12 deficiency, 80% presented with spells (37%) of apneas, motor seizures, or absences within the first two months of life. Tremor (29%) and irritability (18%) were the most common findings at the first examination. Serum total homocysteine ≥10 μmol/L was found in 77% of cases compared to 28% of controls (P < 0.001). None of the mothers were vegetarians, but 25% reported a previous history of vitamin B12 deficiency and 7% had celiac disease. The dose of nitrous oxide given during labor was significantly associated with infant serum total homocysteine level at diagnosis (r = 0.37, 95% confidence interval = 0.16-0.55, P < 0.001) for cases, but not for controls.
Conclusion: Spells, tremor, and irritability are common findings in early infant vitamin B12 deficiency. Nitrous oxide given during labor is proposed as a contributing risk factor to the development of early infant vitamin B12 deficiency