OBJECTIVE:To delineate the risk to child IQ associated with frequently prescribed antiepileptic drugs.
METHODS:Children born to women with epilepsy (n = 243) and women without epilepsy (n = 287) were ...recruited during pregnancy and followed prospectively. Of these, 408 were blindly assessed at 6 years of age. Maternal and child demographics were collected and entered into statistical models.
RESULTS:The adjusted mean IQ was 9.7 points lower (95% confidence interval CI −4.9 to −14.6; p < 0.001) for children exposed to high-dose (>800 mg daily) valproate, with a similar significant effect observed for the verbal, nonverbal, and spatial subscales. Children exposed to high-dose valproate had an 8-fold increased need of educational intervention relative to control children (adjusted relative risk, 95% CI 8.0, 2.5–19.7; p < 0.001). Valproate at doses <800 mg daily was not associated with reduced IQ, but was associated with impaired verbal abilities (−5.6, 95% CI −11.1 to −0.1; p = 0.04) and a 6-fold increase in educational intervention (95% CI 1.4–18.0; p = 0.01). In utero exposure to carbamazepine or lamotrigine did not have a significant effect on IQ, but carbamazepine was associated with reduced verbal abilities (−4.2, 95% CI −0.6 to −7.8; p = 0.02) and increased frequency of IQ <85.
CONCLUSIONS:Consistent with data from younger cohorts, school-aged children exposed to valproate at maternal doses more than 800 mg daily continue to experience significantly poorer cognitive development than control children or children exposed to lamotrigine and carbamazepine.
The aim of this study was to compare the prevalence of diagnosed neurodevelopmental disorders in children exposed, in utero, to different antiepileptic drug treatments. A prospective cohort of women ...with epilepsy and a control group of women without epilepsy were recruited from antenatal clinics. The children of this cohort were followed longitudinally until 6 years of age (n=415). Diagnosis of a neurodevelopmental disorder was made independently of the research team. Multiple logistic regression analysis revealed an increase in risk of neurodevelopmental disorders in children exposed to monotherapy sodium valproate (VPA) (6/50, 12.0%; aOR 6.05, 95%CI 1.65 to 24.53, p=0.007) and in those exposed to polytherapy with sodium VPA (3/20, 15.0%; aOR 9.97, 95% CI 1.82 to 49.40, p=0.005) compared with control children (4/214; 1.87%). Autistic spectrum disorder was the most frequent diagnosis. No significant increase was found among children exposed to carbamazepine (1/50) or lamotrigine (2/30). An accumulation of evidence demonstrates that the risks associated with prenatal sodium VPA exposure include an increased prevalence of neurodevelopmental disorders. Whether such disorders are discrete or represent the severe end of a continuum of altered neurodevelopmental functioning requires further investigation. Replication and extension of this research is required to investigate the mechanism(s) underpinning the relationship. Finally, the increased likelihood of neurodevelopmental disorders should be communicated to women for whom sodium VPA is a treatment option.
This study sought to establish the long-term effects of Covid-19 following hospitalisation.
327 hospitalised participants, with SARS-CoV-2 infection were recruited into a prospective multicentre ...cohort study at least 3 months post-discharge. The primary outcome was self-reported recovery at least ninety days after initial Covid-19 symptom onset. Secondary outcomes included new symptoms, disability (Washington group short scale), breathlessness (MRC Dyspnoea scale) and quality of life (EQ5D-5L).
55% of participants reported not feeling fully recovered. 93% reported persistent symptoms, with fatigue the most common (83%), followed by breathlessness (54%). 47% reported an increase in MRC dyspnoea scale of at least one grade. New or worse disability was reported by 24% of participants. The EQ5D-5L summary index was significantly worse following acute illness (median difference 0.1 points on a scale of 0 to 1, IQR: -0.2 to 0.0). Females under the age of 50 years were five times less likely to report feeling recovered (adjusted OR 5.09, 95% CI 1.64 to 15.74), were more likely to have greater disability (adjusted OR 4.22, 95% CI 1.12 to 15.94), twice as likely to report worse fatigue (adjusted OR 2.06, 95% CI 0.81 to 3.31) and seven times more likely to become more breathless (adjusted OR 7.15, 95% CI 2.24 to 22.83) than men of the same age.
Survivors of Covid-19 experienced long-term symptoms, new disability, increased breathlessness, and reduced quality of life. These findings were present in young, previously healthy working age adults, and were most common in younger females.
National Institute for Health Research, UK Medical Research Council, Wellcome Trust, Department for International Development and the Bill and Melinda Gates Foundation.
Viral meningitis is increasingly recognised, but little is known about the frequency with which it occurs, or the causes and outcomes in the UK. We aimed to determine the incidence, causes, and ...sequelae in UK adults to improve the management of patients and assist in health service planning.
We did a multicentre prospective observational cohort study of adults with suspected meningitis at 42 hospitals across England. Nested within this study, in the National Health Service (NHS) northwest region (now part of NHS England North), was an epidemiological study. Patients were eligible if they were aged 16 years or older, had clinically suspected meningitis, and either underwent a lumbar puncture or, if lumbar puncture was contraindicated, had clinically suspected meningitis and an appropriate pathogen identified either in blood culture or on blood PCR. Individuals with ventricular devices were excluded. We calculated the incidence of viral meningitis using data from patients from the northwest region only and used these data to estimate the population-standardised number of cases in the UK. Patients self-reported quality-of-life and neuropsychological outcomes, using the EuroQol EQ-5D-3L, the 36-Item Short Form Health Survey (SF-36), and the Aldenkamp and Baker neuropsychological assessment schedule, for 1 year after admission.
1126 patients were enrolled between Sept 30, 2011, and Sept 30, 2014. 638 (57%) patients had meningitis: 231 (36%) cases were viral, 99 (16%) were bacterial, and 267 (42%) had an unknown cause. 41 (6%) cases had other causes. The estimated annual incidence of viral meningitis was 2·73 per 100 000 and that of bacterial meningitis was 1·24 per 100 000. The median length of hospital stay for patients with viral meningitis was 4 days (IQR 3–7), increasing to 9 days (6–12) in those treated with antivirals. Earlier lumbar puncture resulted in more patients having a specific cause identified than did those who had a delayed lumbar puncture. Compared with the age-matched UK population, patients with viral meningitis had a mean loss of 0·2 quality-adjusted life-years (SD 0·04) in that first year.
Viruses are the most commonly identified cause of meningitis in UK adults, and lead to substantial long-term morbidity. Delays in getting a lumbar puncture and unnecessary treatment with antivirals were associated with longer hospital stays. Rapid diagnostics and rationalising treatments might reduce the burden of meningitis on health services.
Meningitis Research Foundation and UK National Institute for Health Research.
English-speaking children’s uninversion errors with wh-questions(e.g., *Who he can draw; c.f., Who can he draw?) are influenced by thesurface frequency of individual bigrams and trigrams in the ...input, aspredicted by input-based approaches. Production methods were used toelicit nonsubject wh-questions from 67 children aged 3;1 to 4;8(M=4;0, SD=4 months). No support was found for the preregisteredprediction that children will produce more uninversion errors whenthose errors incorporate – in the Bigram 3 position – high-frequencybigrams from uninverted structures (e.g., *Who he can draw?) thanlower-frequency bigrams from uninverted structures (e.g., *Who he canname?), with all other bigram and unigram frequencies matched for eachpair. However, a non-preregistered exploratory analysis found afacilitatory effect on correct-question production of the frequency ofthe second and third bigrams from inverted structures (e.g., can he…hedraw), even after controlling for unigram frequency. This analysisalso found that rates of uninversion error (e.g., *Who he can draw?)were higher when the first uninverted bigram (e.g., Who he…) is ofhigher frequency in the input. We conclude that while input-basedaccounts are correct to highlight the importance of n-gram inputfrequencies on rates of correct production versus uninversion error,it is unclear on current evidence which n-grams are driving errors andwhy. In particular, the special emphasis placed by some such accountson n-grams at the left-edge of the utterance (e..g, Who can…) may beunwarranted.
ABSTRACT
A central question in language acquisition is how children master sentence types that they have seldom, if ever, heard. Here we report the findings of a pre-registered, randomised, ...single-blind intervention study designed to test the prediction that, for one such sentence type, complex questions (e.g.,
Is the crocodile who’s hot eating?
), children could combine schemas learned, on the basis of the input, for complex noun phrases (
the THING who’s PROPERTY
) and simple questions (
Is THING ACTIONing?
) to yield a complex-question schema (
Is the THING who’s PROPERTY ACTIONing?
). Children aged 4;2 to 6;8 (
M
= 5;6,
SD
= 7.7 months) were trained on simple questions (e.g.,
Is the bird cleaning?
) and either (Experimental group,
N
= 61) complex noun phrases (e.g.,
the bird who’s sad
) or (Control group,
N
= 61) matched simple noun phrases (e.g.,
the sad bird
). In general, the two groups did not differ on their ability to produce novel complex questions at test. However, the Experimental group did show (a) some evidence of generalising a particular complex NP schema (
the THING who’s PROPERTY
as opposed to
the THING that’s PROPERTY
) from training to test, (b) a lower rate of auxiliary-doubling errors (e.g.,
*Is the crocodile who’s hot is eating?
), and (c) a greater ability to produce complex questions on the first test trial. We end by suggesting some different methods – specifically artificial language learning and syntactic priming – that could potentially be used to better test the present account.
Our aim was to compare neuropsychological and psychiatric outcomes across three encephalitis aetiological groups: Herpes simplex virus (HSV), other infections or autoimmune causes (Other), and ...encephalitis of unknown cause (Unknown).
Patients recruited from NHS hospitals underwent neuropsychological and psychiatric assessment in the short-term (4 months post-discharge), medium-term (9-12 months after the first assessment), and long-term (>1-year). Healthy control subjects were recruited from the general population and completed the same assessments.
Patients with HSV were most severely impaired on anterograde and retrograde memory tasks. In the short-term, they also showed executive, IQ, and naming deficits, which resolved in the long-term. Patients with Other or Unknown causes of encephalitis showed moderate memory impairments, but no significant impairment on executive tests. Memory impairment was associated with hippocampal/medial temporal damage on magnetic resonance imaging (MRI), and naming impairment with left temporal and left frontal abnormalities. Patients reported more subjective cognitive complaints than healthy controls, with tiredness a significant problem, and there were high rates of depression and anxiety in the HSV and the Other encephalitis groups. These subjective, self-reported complaints, depression, and anxiety persisted even after objectively measured neuropsychological performance had improved.
Neuropsychological and psychiatric outcomes after encephalitis vary according to aetiology. Memory and naming are severely affected in HSV, and less so in other forms. Neuropsychological functioning improves over time, particularly in those with more severe short-term impairments, but subjective cognitive complaints, depression, and anxiety persist, and should be addressed in rehabilitation programmes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study was a prospective observational multicenter study in the USA and UK, which enrolled pregnant women with epilepsy on antiepileptic ...drug (AED) monotherapy from 1999 to 2004. The study aimed to determine if differential long-term neurodevelopmental effects exist across four commonly used AEDs (carbamazepine, lamotrigine, phenytoin, and valproate). In this report, we examine fetal AED exposure effects on learning and memory functions in 221 six-year-old children (including four sets of twins) whose mothers took one of these AEDs during pregnancy. Their performance was compared with that of a national sample of normally developing six year olds from the standardization sample of the Children's Memory Scale (CMS). The major results of this study indicate that the mean performance levels of children exposed to valproate were significantly below that of the children in the normal comparison group across all seven of the CMS Indexes. With one exception, this finding held up at the subtest level as well. These findings taken together with nonsignificant verbal and nonverbal forgetting scores appear to indicate that, as a group, children exposed to valproate experienced significant difficulty in their ability to process, encode, and learn both auditory/verbal as well as visual/nonverbal material. In addition, they exhibited significant difficulty holding and manipulating information in immediate auditory working memory. However, once the information was learned and stored, the valproate-exposed children appeared to be able to retrieve the information they did learn at normal levels. Finally, the processing, working memory, and learning deficits demonstrated by the valproate-exposed children are dose-related. In contrast to valproate, the findings pertaining to the children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy are less clear. Therefore, further research will be required to delineate the potential risks to learning and memory functions in children exposed to carbamazepine, lamotrigine, and phenytoin in monotherapy during pregnancy. Additional research employing larger prospective studies will be required to confirm the long-term cognitive and behavioral risks to children of mothers who are prescribed these four AEDs during pregnancy as well as to delineate any potential risks of newer AEDs and to understand the underlying mechanisms of adverse AED effects on the immature brain.
•Fetal valproate exposure is associated with difficulty with learning and working memory.•Valproate-exposed children retrieve learned information at normal levels.•Learning and memory deficits associated with fetal valproate exposure are dose-related.•Risks to learning and memory from fetal exposure to other antiepileptic drugs are unclear.
This article discusses the management of acute confusion and aggression in patients with infections of the central nervous system (CNS). The issues discussed are applicable to the management of acute ...confusion of any cause and the principles of care apply to all confused patients. The article addresses many of the challenges encountered by nurses caring for confused patients, including the recognition of acute confusion, use of screening tools, and the management and treatment of these patients.
To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid ...therapy.
The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting.
Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids.
This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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