Gabriel Chow

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.

The relation between pump flow rate and pulsatility on cerebral hemodynamics during pediatric cardiopulmonary bypass

OBJECTIVES Neurologic impairment, at least partly ischemic in origin, has been reported in up to 25% of infants undergoing cardiopulmonary bypass, with or without circulatory arrest. Controversy continues about the effect of pump flow, pulsatile or nonpulsatile, on the brain and in particular on cerebral blood flow. This study examines the relationship between pump flow rate and cerebral hemodynamics during pulsatile and nonpulsatile cardiopulmonary bypass. METHOD Near-infrared spectroscopy was used to determine cerebral blood flow and cerebral blood volume (measured as concentration change) in a randomized crossover study. Pulsatile and nonpulsatile flow were used for six 5-minute intervals at each of three different pump flow rates (0.6, 1.2, and 2.4 L x m2 x min(-1)) in 40 patients, median age 2 months (range 2 weeks to 20 years 5 months). The relations between pulsatile flow, pump flow rate, cerebral blood flow, hemoglobin concentration change (cerebral blood volume), mean arterial pressure, arterial carbon dioxide tension, and hematocrit value were prospectively examined by means of multivariate analysis. RESULTS Cerebral blood flow decreased 36% per L x m(-2) x min(-1) decrease in pump flow rate and was associated with changes in mean arterial pressure but did not differ according to pulsatility. Change in hemoglobin concentration was unrelated to changes in pulsatility of pump flow. CONCLUSION Cerebral blood flow is related to pump flow rate. Pulsatile flow delivered with a Stöckert pump does not increase cerebral blood flow or alter hemoglobin concentration during cardiopulmonary bypass in children.

Congenital Myasthenic Syndrome Type 19 Is Caused by Mutations in COL13A1, Encoding the Atypical Non-fibrillar Collagen Type XIII α1 Chain

The neuromuscular junction (NMJ) consists of a tripartite synapse with a presynaptic nerve terminal, Schwann cells that ensheathe the terminal bouton, and a highly specialized postsynaptic membrane. Synaptic structural integrity is crucial for efficient signal transmission. Congenital myasthenic syndromes (CMSs) are a heterogeneous group of inherited disorders that result from impaired neuromuscular transmission, caused by mutations in genes encoding proteins that are involved in synaptic transmission and in forming and maintaining the structural integrity of NMJs. To identify further causes of CMSs, we performed whole-exome sequencing (WES) in families without an identified mutation in known CMS-associated genes. In two families affected by a previously undefined CMS, we identified homozygous loss-of-function mutations in COL13A1, which encodes the alpha chain of an atypical non-fibrillar collagen with a single transmembrane domain. COL13A1 localized to the human muscle motor endplate. Using CRISPR-Cas9 genome editing, modeling of the COL13A1 c.1171delG (p.Leu392Sfs∗71) frameshift mutation in the C2C12 cell line reduced acetylcholine receptor (AChR) clustering during myotube differentiation. This highlights the crucial role of collagen XIII in the formation and maintenance of the NMJ. Our results therefore delineate a myasthenic disorder that is caused by loss-of-function mutations in COL13A1, encoding a protein involved in organization of the NMJ, and emphasize the importance of appropriate symptomatic treatment for these individuals.

Longitudinal analysis of the neurological features of ataxia-telangiectasia

To assess the relationship between genotype and neurological progression in ataxia‐telangiectasia (A‐T).

Fifteen-minute consultation: the child with idiopathic intracranial hypertension

Idiopathic intracranial hypertension (IIH) is a rare condition where intracranial hypertension is found in the context of normal brain parenchyma and no mass lesion, ventriculomegaly, underlying infection, or malignancy. Our understanding of this condition has greatly improved in the recent years with neuroimaging features and normal values for lumbar puncture opening pressure now well defined. This article provides a review of IIH in children and revised diagnostic criteria based on recent evidence and published opinion. We have also presented an algorithmic approach to the child with possible IIH.

Dual Diagnosis of Dihydropyrimidine Dehydrogenase Deficiency and GM1 Gangliosidosis

An 8-month-old girl, born to consanguineous parents, presented with developmental delay, decreased muscle tone, disinterest in her surroundings, and sleepiness. Tests revealed a marked excretion of thymine with significantly increased uracil excretion in the urine, indicating a pyrimidine catabolic disorder, i.e., dihydropyrimidine dehydrogenase deficiency. Plasma endogenous purines confirmed elevated plasma thymine (21 μmol/L) and uracil (29 μmol/L), also consistent with dihydropyrimidine dehydrogenase deficiency. Purine mutation analysis confirmed complete dihydropyrimidine dehydrogenase deficiency with a 16 [ corrected] base pair homozygous deletion in exon 16, corresponding to DPYD c.2043-2058del. Cranial magnetic resonance imaging at 14 months indicated severe hypomyelination with gliosis. Her basal ganglia were also involved. At age 15 months, she was hospitalized for aspiration pneumonia and seizures, and also manifested hepatosplenomegaly. White cell enzymes revealed a marked deficiency of β-galactosidase activity (4 μmol/g/hour) in white cells and an elevated chitotriosidase activity (443 μmol/L/hour) in plasma indicating GM(1) gangliosidosis. Mutation analysis confirmed c.841C>T (p.His281Tyr) homozygosity for GM(1) gangliosidosis. She died at age 19 months.

NEUROLOGICAL MANIFESTATIONS OF INFLUENZA INFECTION IN ADULTS AND CHILDREN: RESULTS OF A NATIONAL BRITISH SURVEILLANCE STUDY

Introduction In recent years an increasing range of neurological syndromes has been associated with the emergence of novel influenza A:H1N1 (2009), and other influenza viruses. We aimed to describe the features of adults and children with neurological manifestations associated with influenza in the UK. Method A surveillance study was performed in conjunction with the BNSU and BPNSU* over a 24–month period (February 2011 to February 2013). Inclusion criteria specified acute neurological illness within 1 month of proven influenza infection and prospective case definitions were applied. Results Twenty–five cases were identified: 4 adults and 21 children [6 (23%) with pre–existing neurological disorders]. Four (16%) cases (all with encephalopathy syndromes) died. Twenty cases (80%) required admission to intensive care. Seventeen (68%) had Glasgow Outcome Scores of 2–5 indicating poor outcome. Polymerase chain reaction (PCR) of respiratory secretions identified: influenza A in 21 (20 H1N1) and influenza B in 4 cases. Two had co–infection with Streptococcus pneumoniae (one adult with septicaemia; one child with meningitis). Cerebrospinal fluid (CSF) revealed a pleocytosis in 3 out of 18 cases (median 184×106 cells/litre [range 16–900]). Influenza PCR was negative in all 10 CSF samples tested. Cerebral magnetic resonance imaging was performed in 3 cases, computerised tomography in 6, and 14 had both. Recognised acute encephalopathy syndromes were seen in 5, and non–specific changes including cerebral oedema and/or diffusion restriction in 5. For the 4 adults, 2 presented with acute extrapyramidal movement disorders, 1 with Guillain–Barré syndrome and 1 with acute encephalopathy. Of the 21 children, 17 presented with acute encephalopathy, 3 with encephalitis and 1 with acute dyskinesia. Encephalopathy syndromes were documented in 7 cases (6 children, 1 adult). They were characterised by their clinical presentation and neuroimaging and included 4 with Acute Necrotising Encephalopathy (ANE), 1 Acute Infantile Encephalopathy Predominantly Affecting the Frontal Lobes (AIEF), 1 Haemorrhagic Shock & Encephalopathy (HSE) syndrome and 1 Acute Haemorrhagic Leukoencephalopathy (AHL). Treatments included: systemic steroids in 4 cases, 1 had intravenous immunoglobulin, and 3 cases received both. None received plasma exchange. Influenza vaccination was indicated in eight cases, but none had received it. Conclusion This paediatric and adult UK cohort identified a severity of influenza related neurological manifestation not reported previously. Cases were more common in children, particularly those with underlying neurological conditions. Encephalopathy syndromes such as ANE, AIEF, HSE and AHL were seen more frequently in children and were associated with a worse outcome. Acute movement disorders and Guillain–Barré syndrome were identified more commonly in adults. Influenza related encephalopathy may be more common in those with abnormal genetically determined host inflammatory responses, but the virus itself is rarely detected in the CSF. Influenza should be considered a cause of acute neurological syndromes in the winter months, especially in children with unexplained encephalopathy. Encephalopathy may be more common with the H1N1 strain. Importantly none of the cases had been vaccinated although many had indications for this.

Trismus in the paediatric population

Trismus is a rare presentation affecting neonates, children, and adults. In newborns there are serious implications, with potential to affect feeding, cause airway problems, and make intubation difficult. Causes of trismus seen in the paediatric patient are discussed in this review article; they are divided into intra‐ and extra‐articular types. The extra‐articular group consists of congenital and acquired disorders. The acquired group includes infective causes such as tetanus, iatrogenic causes related to drugs, cancer or dental treatment, and trauma causing articulation difficulty or triggering a rare type of bone growth in myositis ossificans. Changes in the mouth resulting from oral submucous fibrosis can undergo malignant transformation. This review aims to raise awareness of potential causes of trismus in paediatric populations, helping clinicians identify the underlying pathology so appropriate strategies for treatment be applied, with the ultimate aim of improving long‐term outlook and quality of life for affected children.

Clinical features, course, and outcomes of a UK cohort of pediatric moyamoya

Objective To describe characteristics and course of a large UK cohort of children with moyamoya from multiple centers and examine prognostic predictors. Methods Retrospective review of case notes/radiology, with use of logistic regression to explore predictors of outcome. Results Eighty-eight children (median presentation age 5.1 years) were included. Thirty-six presented with arterial ischemic stroke (AIS) and 29 with TIA. Eighty had bilateral and 8 unilateral carotid circulation disease; 29 patients had posterior circulation involvement. Acute infarction was present in 36/176 hemispheres and chronic infarction in 86/176 hemispheres at the index presentation. Sixty-two of 82 with symptomatic presentation had at least one clinical recurrence. Fifty-five patients were treated surgically, with 37 experiencing fewer recurrences after surgery. Outcome was categorized as good using the Recovery and Recurrence Questionnaire in 39/85 patients. On multivariable analysis, presentation with TIA (odds ratio [OR] 0.09, 95% confidence interval [CI] 0.02–0.35), headache (OR 0.10, 95% CI 0.02–0.58), or no symptoms (OR 0.08, 95% CI 0.01–0.68) was less likely to predict poor outcome than AIS presentation. Posterior circulation involvement predicted poor outcome (OR 4.22, 95% CI 1.23–15.53). Surgical revascularization was not a significant predictor of outcome. Conclusions Moyamoya is associated with multiple recurrences, progressive arteriopathy, and poor outcome in half of patients, especially with AIS presentation and posterior circulation involvement. Recurrent AIS is rare after surgery. Surgery was not a determinant of overall outcome, likely reflecting surgical case selection and presentation clinical status.

Neonatal seizure: what is the cause?

A 7 day old girl presented with a one day history of decreased feeding, lethargy, and shaking of her extremities. She was born at term by normal vaginal delivery. She did not have a fever and there were no maternal risk factors for sepsis. She was hypotonic and minimally responsive on examination, with no signs of focal neurology. Urea, electrolytes, calcium, and glucose values were normal. She was started empirically on intravenous antibiotics and aciclovir after full septic screen. She was ventilated and given an infusion of midazolam because her generalised clonic seizures with apnoea failed to respond to intravenous phenobarbital. Her seizures finally responded and she was extubated after 24 hours; she was maintained on regular phenobarbital with good effect. Urgent neuroimaging (figs 1⇓ and 2⇓) was arranged because of her acute presentation with seizures and a history of deep vein thrombosis and pulmonary embolism in her mother and maternal uncle. Fig 1 Sagittal T1 weighted magnetic resonance image of the brain Fig 2 Axial T1 weighted magnetic resonance image of the brain ### 1 What are the causes of seizures in a neonate? #### Short answer Common causes of neonatal seizures include hypoxic ischaemic encephalopathy, intracranial haemorrhage, intracranial infections, congenital cerebral malformations, metabolic disorders, and focal ischaemic stroke. #### Long answer Seizures are more common in the neonatal period than in any other time of life, with 80% occurring in the first week of life. This is because the immature …