Neurological manifestations of influenza infection in children and adults: results of a National British Surveillance Study.

BACKGROUND: The emergence of influenza A(H1N1) 2009 was met with increased reports of associated neurological manifestations. We aimed to describe neurological manifestations of influenza in adults and children in the United Kingdom that presented at this time. METHODS: A 2-year surveillance study was undertaken through the British adult and pediatric neurological surveillance units from February 2011. Patients were included if they met clinical case definitions within 1 month of proven influenza infection. RESULTS: Twenty-five cases were identified: 21 (84%) in children and 4 (16%) in adults. Six (29%) children had preexisting neurological disorders. Polymerase chain reaction of respiratory secretions identified influenza A in 21 (81%; 20 of which [95%] were H1N1) and influenza B in 4 (15%). Twelve children had encephalopathy (1 with movement disorder), 8 had encephalitis, and 1 had meningoencephalitis. Two adults had encephalopathy with movement disorder, 1 had encephalitis, and 1 had Guillain-Barré syndrome. Seven individuals (6 children) had specific acute encephalopathy syndromes (4 acute necrotizing encephalopathy, 1 acute infantile encephalopathy predominantly affecting the frontal lobes, 1 hemorrhagic shock and encephalopathy, 1 acute hemorrhagic leukoencephalopathy). Twenty (80%) required intensive care, 17 (68%) had poor outcome, and 4 (16%) died. CONCLUSIONS: This surveillance study described a cohort of adults and children with neurological manifestations of influenza. The majority were due to H1N1. More children than adults were identified; many children had specific encephalopathy syndromes with poor outcomes. None had been vaccinated, although 8 (32%) had indications for this. A modified classification system is proposed based on our data and the increasing spectrum of recognized acute encephalopathy syndromes.

Benign hereditary chorea related to NKX2.1: expansion of the genotypic and phenotypic spectrum.

AIM: Benign hereditary chorea is a dominantly inherited, childhood-onset hyperkinetic movement disorder characterized by non-progressive chorea and variable degrees of thyroid and respiratory involvement. Loss-of-function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals. METHOD: Clinical data from individuals with benign hereditary chorea identified through paediatric neurology services were collected in a standardized format. The NKX2.1 gene was analysed by Sanger sequencing, multiplex ligation-dependent probe amplification, and microarray analysis. RESULTS: Six of our cohort were female and four male, median age at assessment was 8 years 6 months (range 1 y 6 mo-18 y). We identified 10 probands with NKX2.1 mutations; nine of these mutations are novel (including two whole-gene deletions) and one has been previously reported. Of the 10 individuals, eight presented with muscle hypotonia and four had evidence of hypothyroidism or respiratory involvement. Only three out of the 10 individuals had the full triad of 'brain-lung-thyroid syndrome' symptoms. Additional clinical characteristics occurring in individual participants included growth hormone deficiency, pes cavus, kyphosis, duplex kidney, and obsessive-compulsive disorder. INTERPRETATION: Our data suggest that the neurological phenotype is prominent in this condition and that many patients with benign hereditary chorea do not have the classic triad of brain-lung-thyroid syndrome. The extended phenotype may include obsessive-compulsive disorder and skeletal abnormalities.

Adherence to antiepileptic medicines in children: a multiple-methods assessment involving dried blood spot sampling.

PURPOSE: To evaluate adherence to prescribed antiepileptic drugs (AEDs) in children with epilepsy using a combination of adherence-assessment methods. METHODS: A total of 100 children with epilepsy (≤17 years old) were recruited. Medication adherence was determined via parental and child self-reporting (≥9 years old), medication refill data from general practitioner (GP) prescribing records, and via AED concentrations in dried blood spot (DBS) samples obtained from children at the clinic and via self- or parental-led sampling in children's own homes. The latter were assessed using population pharmacokinetic modeling. Patients were deemed nonadherent if any of these measures were indicative of nonadherence with the prescribed treatment. In addition, beliefs about medicines, parental confidence in seizure management, and the presence of depressed mood in parents were evaluated to examine their association with nonadherence in the participating children. KEY FINDINGS: The overall rate of nonadherence in children with epilepsy was 33%. Logistic regression analysis indicated that children with generalized epilepsy (vs. focal epilepsy) were more likely (odds ratio [OR] 4.7, 95% confidence interval [CI] 1.37-15.81) to be classified as nonadherent as were children whose parents have depressed mood (OR 3.6, 95% CI 1.16-11.41). SIGNIFICANCE: This is the first study to apply the novel methodology of determining adherence via AED concentrations in clinic and home DBS samples. The present findings show that the latter, with further development, could be a useful approach to adherence assessment when combined with other measures including parent and child self-reporting. Seizure type and parental depressed mood were strongly predictive of nonadherence.

Sydenham's chorea: not gone but perhaps forgotten.

Sydenham's chorea (SC) is characterised by chorea, emotional lability and hypotonia. In this study, we investigated the incidence and clinical presentation of childhood SC in Ireland (years 2006-2014). Nineteen cases were diagnosed. Five patients had rheumatic fever. An increasing trend with an incidence of 0.23/100 000 is reported. As most referral diagnoses included psychogenic illness, head injury and stroke, modern physicians may not be aware of this age old illness. A review of the manifestations and diagnosis of SC is presented.

An unusual family with multiple movement disorders.

Multiple movement disorders presenting in the same family are rare. We present an unusual family where generalized dystonia, Huntington's disease, progressive supranuclear palsy and secondary paroxysmal dyskinesia co-exist. The index case presented with young-onset dystonia and tested negative for the DYT1 gene deletion. Her father was similarly affected. The father's brother (paternal uncle of the index) also had abnormal movements-a mixture of chorea and dystonia-and tested positive for the HD expansion. His son had secondary paroxysmal dyskinesia, and tested negative for the HD expansion. The index case and her father were also negative for the HD expansion. A paternal aunt of two of the cases had a clinical diagnosis of progressive supranuclear palsy. Dystonia is known to be a genetically heterogeneous condition. The co-existence of inherited generalized dystonia with other movement disorders may provide clues to its genetic localization.

Neurologic problems after pediatric liver transplantation and combined liver and bowel transplantations: a single tertiary centre experience.

BACKGROUND: Neurologic problems postpediatric liver transplant have been reported in up to 46% of cases, and mortality is higher in the pediatric age group compared with adults. METHODS: An internal audit was performed in all children undergoing solid organ transplant in the Liver unit at Birmingham Children's Hospital to identify children with neurologic complications. RESULTS: One hundred seventeen children underwent 127 pediatric liver transplant and combined liver and small bowel transplant episodes over a 4-year period. Neurologic problems were present after 31 of 127 (24.4%) transplant episodes involving 29 children. Seizures were the most common presentation (n=17; 54.8%), followed by encephalopathy (n=11; 35.4%) and posterior reversible leukoencephalopathy syndrome (n=6; 19.3%). Other complications noted were central nervous system infection (n=4; 12.9%), cerebrovascular accident (n=3; 9.6%), peripheral neuropathy (n=2; 6.4%) and tremor, transient blurring of vision, auditory hallucinations and choreoathetosis (n=1; 3.2%) each. There were 27 deaths (23%) in 117 children after transplantation, and the mortality rate in the group with neurologic problem was 13.3% (n=4) compared with 26.7% (n=23) in children without neurologic problem (odds ratio 0.45, 95% confidence interval 0.142-1.439). In contrast to other studies, our study showed that the mortality rate was not higher in children with neurologic problems. CONCLUSION: Neurologic problems were relatively common after pediatric liver transplantation and combined liver and bowel transplantations; however, the mortality was lower when compared with previously reported studies.