Functional neurological disorder in children and young people: Incidence, clinical features, and prognosis.

AIM: To report incidence, demographic and clinical characteristics, and symptom outcome of functional neurological disorder (FND) in children. METHOD: Children diagnosed with FND at a regional children's hospital were prospectively recruited by weekly active surveillance for 36 months. Demographic, clinical, and follow-up data were retrospectively extracted by review of electronic records. Descriptive statistical analyses were used. RESULTS: Ninety-seven children (age range 5-15 years) met the case definition of FND (annual incidence 18.3 per 100 000 children). Children with FND were likely to be female (n = 68 [70%]) and older (median 13 years) with no difference in the Scottish Index of Multiple Deprivation (marker of socioeconomic status) compared with the general childhood population. Functional motor (41%) and sensory (41%) symptoms were most common; other somatic symptoms such as headache (31%) and pain (27%) were frequent. Self-reported psychiatric symptoms and infection/inflammation were the most common predisposing and precipitating factors respectively. At a median of 15 months follow-up, 49% of 75 children reported improvement or resolution of FND symptoms with no prognostic factors found. INTERPRETATION: At this regional centre, FND in children had a higher incidence than previously reported and a less optimistic outcome than in some other studies.

Early childhood epilepsies: epidemiology, classification, aetiology, and socio-economic determinants.

Epilepsies of early childhood are frequently resistant to therapy and often associated with cognitive and behavioural comorbidity. Aetiology focused precision medicine, notably gene-based therapies, may prevent seizures and comorbidities. Epidemiological data utilizing modern diagnostic techniques including whole genome sequencing and neuroimaging can inform diagnostic strategies and therapeutic trials. We present a 3-year, multicentre prospective cohort study, involving all children under 3 years of age in Scotland presenting with epilepsies. We used two independent sources for case identification: clinical reporting and EEG record review. Capture-recapture methodology was then used to improve the accuracy of incidence estimates. Socio-demographic and clinical details were obtained at presentation, and 24 months later. Children were extensively investigated for aetiology. Whole genome sequencing was offered for all patients with drug-resistant epilepsy for whom no aetiology could yet be identified. Multivariate logistic regression modelling was used to determine associations between clinical features, aetiology, and outcome. Three hundred and ninety children were recruited over 3 years. The adjusted incidence of epilepsies presenting in the first 3 years of life was 239 per 100 000 live births [95% confidence interval (CI) 216-263]. There was a socio-economic gradient to incidence, with a significantly higher incidence in the most deprived quintile (301 per 100 000 live births, 95% CI 251-357) compared with the least deprived quintile (182 per 100 000 live births, 95% CI 139-233), χ2 odds ratio = 1.7 (95% CI 1.3-2.2). The relationship between deprivation and incidence was only observed in the group without identified aetiology, suggesting that populations living in higher deprivation areas have greater multifactorial risk for epilepsy. Aetiology was determined in 54% of children, and epilepsy syndrome was classified in 54%. Thirty-one per cent had an identified genetic cause for their epilepsy. We present novel data on the aetiological spectrum of the most commonly presenting epilepsies of early childhood. Twenty-four months after presentation, 36% of children had drug-resistant epilepsy (DRE), and 49% had global developmental delay (GDD). Identification of an aetiology was the strongest determinant of both DRE and GDD. Aetiology was determined in 82% of those with DRE, and 75% of those with GDD. In young children with epilepsy, genetic testing should be prioritized as it has the highest yield of any investigation and is most likely to inform precision therapy and prognosis. Epilepsies in early childhood are 30% more common than previously reported. Epilepsies of undetermined aetiology present more frequently in deprived communities. This likely reflects increased multifactorial risk within these populations.

Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies.

Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), presumed monogenic T1Is (pT1I), childhood systemic lupus erythematosus with neuropsychiatric features (nSLE), non-IFN-related autoinflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital ELISA. Eighty-two and 63 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison (taking one sample per individual), median CSF IFN-alpha levels were elevated in AGS, SAVI, pT1I, and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I, and nSLE. Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, our data suggest the primary sites of IFN production in the monogenic T1I AGS and SAVI are, respectively, the CNS and the periphery. These results inform the diagnosis of, and future therapeutic approaches to, monogenic and multifactorial T1Is.

Are you tuned in? The challenges of seizure identification in children with intellectual disability - A potential for video-based care-pathway.

This qualitative study explores the challenges parents/carers face in seizure identification in children with coexisting epilepsy and intellectual disability (ID). Semi-structured interviews with parents/carers provided ten hours of data, transcribed verbatim for data analysis. Themes and subthemes were identified and grouped to reflect the findings. The importance of knowing the child's usual behavior and recognizing changes to this was a consistent theme. All participants reported that being 'in tune' with their child helped in seizure recognition. Participants felt that the healthcare professionals (HCP) were poor at recognizing seizures in their children at times. They had mixed thoughts on the difficulty the presence of an ID contributes to seizure recognition. The severity of ID and the seizure type were the two main variables discussed. The study concludes that knowing the child well and understanding the usual behavior of the child is crucial to seizure recognition. A video-based care pathway with videos of both usual behavior and seizure activity available to the HCP to classify the events correctly may be potentially beneficial to improve patient care.

Children's understanding of epilepsy: A qualitative study.

PURPOSE: To use a qualitative research approach to determine children's understandings of epilepsy and their epilepsy treatment. METHODS: Children aged 7-16 years with physician-confirmed active epilepsy (i.e., having had an epileptic seizure in the past year and or currently taking antiepileptic drugs (AEDs), and not known to have an intellectual disability, were invited to participate. Children had semi-structured interviews separately on two occasions. Between the first and second interviews, an observation of a routine epilepsy clinic appointment of individual children was conducted, and was then discussed during the second interview. Participatory research tools were used in both child interviews to facilitate discussions. Interviews were audio recorded and transcribed, pseudonymized and entered into NVivo (version 12, QSR International). Data were analyzed using a thematic approach. RESULTS: Twenty-three children of mean age 10.1 years (range 8-14), mean duration of epilepsy of 4.6 years (range 2-10) were enrolled. Twelve were 12 female; 7 had focal, 14 had generalized, and 2 had combined epilepsy; 20 were on monotherapy; and 16 had tried previous AEDs. All had an initial (first) interview; 20 were observed during a clinic appointment and had a second interview. Five broad themes emerged: understanding of epilepsy; understanding of seizures; understanding of medication; understanding of children's role in clinical appointments; influences on children's understanding. Children spoke about what epilepsy meant by describing the physical sensations of having a seizure or through the act of taking medication. Children described the role they had, or felt they should have, but reported challenges in being meaningfully involved in clinical appointments. While healthcare professionals were initial information nodes, epilepsy information from parents appeared to be more significant for children. CONCLUSIONS: The perspectives of children with epilepsy are valuable for clinicians to understand; assumptions should not be made that children's views can be accessed via parents. Clinicians need to be constantly aware of children's views and ways of understanding and communicating about their epilepsy. To support this, the research - drawing on children's words, meanings, and stories - was used to inform an easily accessible, gender-neutral, animation about epilepsy that provides information about the condition, seizures, and medication (https://youtu.be/MO7xXL2ZXP8).

Pilot project of psychological services integrated into a pediatric epilepsy clinic: Psychology Adding Value - Epilepsy Screening (PAVES).

RATIONALE: Children and young people with epilepsy (CYPwE) are particularly vulnerable to developing social, emotional, behavioral, and learning difficulties, which, if not identified or addressed at an early stage, can impact adversely on quality of life and long-term psychosocial outcomes. This paper describes the development of a screening protocol and a pathway of early, 'stepped' intervention, which aims to address this issue, together with initial outcomes. METHODS: The Strengths and Difficulties Questionnaire (SDQ) was completed by CYPwE and their parents prior to routine epilepsy clinic appointments. A traffic light system was devised to indicate the reported level of concern and a potential route through the early intervention pathway. RESULTS: Of those CYPwE screened, 53% were found to be experiencing elevated levels of mental health difficulties, which had not previously been identified, and had the opportunity to access an appropriate early intervention. Initial feedback on the PAVES pathway has been positive, with high levels of feasibility and acceptability indicated by young people, parents, and clinicians. CONCLUSIONS: The PAVES approach enables mental health difficulties to be identified and appropriate intervention accessed at an early stage, potentially improving long-term psychosocial outcomes for CYPwE. In addition, if found to be effective in larger trials, PAVES has potential to be adapted and generalized to other populations.

Epidemiology and outcome of status epilepticus in children: a Scottish population cohort study.

AIM: To describe the epidemiology and outcomes of convulsive status epilepticus (CSE) since the introduction of buccal midazolam and the change in International League Against Epilepsy definition of CSE to include seizures of at least 5 minutes. METHOD: All children presenting to paediatric emergency departments with CSE (2011-2017) in Lothian, Scotland, were identified. Data, collated from electronic health records, included patient demographics, clinical characteristics, acute seizure management, and adverse outcomes (for example admission to intensive care). RESULTS: Six hundred and sixty-five children were admitted with CSE who had 1228 seizure episodes (381 males, 284 females; median age 3y 8mo; age range 0-20y 11mo). CSE accounted for 0.38% (95% confidence interval 0.34-0.42) of annual attendances at emergency departments. Annual prevalence was 0.8 per 1000 children aged 0 to 14 years. Thirty-four per cent of children had recurrent CSE. Sixty-nine per cent of seizures lasted 5 to 29 minutes (median duration 10min). Buccal midazolam was given to 30% of children with CSE and had no effect on need for ventilatory support. Seventy per cent of children with CSE required hospital admission. Four per cent resulted in adverse outcome and there were only two deaths. Recurrent seizures, longer duration, and unprovoked seizures increased the odds of adverse outcome. INTERPRETATION: Adverse outcomes have decreased and the use of buccal midazolam is promising. Identifying high-risk groups provides an opportunity for early intervention. These data form the basis for an extensive evaluation of acute seizure management and monitoring long-term outcomes. What this paper adds The annual prevalence of convulsive status epilepticus in Lothian, Scotland, was 0.8 per 1000 children. There was a decrease in case-fatality proportion from 3-9% to 0.2%. Use of buccal midazolam has increased, with no increase in adverse outcomes.

Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort.

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (>10 min) febrile seizures; febrile or afebrile status epilepticus (>30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children's hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9-57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26-14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93-12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24-9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07-7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy.

Analysis of EEG networks and their correlation with cognitive impairment in preschool children with epilepsy.

OBJECTIVE: Cognitive impairment (CI) is common in children with epilepsy and can have devastating effects on their quality of life. Early identification of CI is a priority to improve outcomes, but the current gold standard of detection with psychometric assessment is resource intensive and not always available. This paper proposes exploiting network analysis techniques to characterize routine clinical electroencephalography (EEG) to help identify CI in children with early-onset epilepsy (CWEOE) (0-5 years old). METHODS: Functional networks from routinely acquired EEGs of 51 newly diagnosed CWEOE were analyzed. Combinations of connectivity metrics with subnetwork analysis identified significant correlations between network properties and cognition scores via rank correlation analysis (Kendall's τ). Predictive properties were investigated using a cross-validated classification model with healthy cognition, mild/moderate CI, and severe CI classes. RESULTS: Network analysis revealed phase-dependent connectivity having higher sensitivity to CI and significant functional network changes across EEG frequencies. Nearly 70.5% of CWEOE were aptly classified as having healthy cognition, mild/moderate CI, or severe CI using network features. These features predicted CI classes 55% better than chance and halved misclassification penalties. CONCLUSIONS: Cognitive impairment in CWEOE can be detected with sensitivity at 85% (in identifying mild/moderate or severe CI) and specificity of 84%, by network analysis. SIGNIFICANCE: This study outlines a data-driven methodology for identifying candidate biomarkers of CI in CWEOE from network features. Following additional replication, the proposed method and its use of routinely acquired EEG forms an attractive proposition for supporting clinical assessment of CI.

Neurobehavioral problems in children with early-onset epilepsy: A population-based study.

PURPOSE: Neurobehavioral problems (i.e., cognitive impairment/behavior problems) are a major challenge in childhood epilepsy. Yet there are limited data in children with early-onset epilepsy (CWEOE; onset ≤4 years), the period in which the incidence of childhood epilepsy is highest. This study aimed to determine the prevalence, spectrum, and risk factors for neurobehavioral problems CWEOE. METHODS: This prospective, population-based, case-controlled study identified children with newly diagnosed early-onset epilepsy in South East Scotland using active multisource capture-recapture surveillance (May 2013 - June 2015). The CWEOE and controls completed an age-appropriate neurobehavioral assessment battery across seven domains: general cognitive ability (GCA), adaptive behavior, externalizing, internalizing, executive functioning, social functioning, and Autism Spectrum Disorder (ASD) risk. RESULTS: Fifty-nine CWEOE were identified with an ascertainment of 98% (95% confidence interval [CI] 94, 103). Forty-six (78% [95% CI 65.9, 86.6]) CWEOE (27 male, median age 25.5, range 1-59, months) and 37 controls (18 male, median age 31.5, range 3-59, months) consented for study entry. The CWEOE were similar to controls in gender, age, prematurity, and family history of psychopathology, but not socioeconomic status (Fisher's exact test [FET] < .001). Neurobehavioral assessments were carried out a median of 2.97 (Interquartile range [IQR] 1.51-4.95) months post epilepsy diagnosis. More CWEOE (63% [95% CI 48.6, 75.5]) had neurobehavioral problems compared with controls (27% [95% CI 15.4, 43.0]); p < 0.01. This observation was independent of socioeconomic status. Multidimensional problems were prevalent in CWEOE with 43% having two or more different domain-level problems; GCA impairment, adaptive behavior, internalizing, social functioning, and ASD risk were particularly marked. Risk factors varied by domain. DISCUSSION: This novel study using comprehensive psychometric assessments found that neurobehavioral problems in CWEOE were detectable, common, and multidimensional. The degree of cooccurrence implies that problems are the norm, and multidimensional screening should be considered at epilepsy onset. The findings could aid policy development on health and educational provision in CWEOE.

Outcome of paediatric acute flaccid myelitis associated with enterovirus D68: a case series.

Enterovirus D68 (EV-D68) is an emerging infection associated with acute flaccid myelitis (AFM). Cases of AFM associated with EV-D68 infection have increased in recent years and the evidence for a causal link is growing. However, our understanding of the epidemiology, clinical features, prognosis, and neurological sequelae of EV-D68 requires ongoing surveillance and investigation. We report five cases of AFM in previously typically developing children (2-6y) from South East Scotland during September and October 2016 after infection with EV-D68 (all detected in the nasopharyngeal aspirates). All cases presented with significant neurological symptoms, which were severe in two cases requiring intensive care support because of respiratory paralysis. At 18-month follow-up, two cases remain ventilator-dependent with other cases requiring ongoing community rehabilitation. These cases represent one of the largest reported paediatric cluster of AFM associated with EV-D68 in Europe. The epidemiology and clinical information add to the knowledge base and the 18-month outcome will help clinicians to counsel families. WHAT THIS PAPER ADDS: Nasopharyngeal aspirate is more sensitive for viral isolation and isolated in all cases. Clinical outcome at 18 months after enterovirus D68 with acute flaccid myelitis provides information on extent of recovery and level of disability.

Cognitive impairment in early onset epilepsy is associated with reduced left thalamic volume.

OBJECTIVE: The objective of this study was to investigate whether reduction of thalamic volumes in children with early onset epilepsy (CWEOE) is associated with cognitive impairment. METHODS: This is a nested case-control study including a prospectively recruited cohort of 76 children with newly-diagnosed early onset epilepsy (onset <5years age) and 14 healthy controls presenting to hospitals within NHS Lothian and Fife. Quantitative volumetric analysis of subcortical structures was performed using volumetric T1-weighted magnetic resonance imaging (MRI) and correlated with the results of formal neurocognitive and clinical assessment. False discovery rate was used to correct for multiple comparisons as appropriate with q<0.05 used to define statistical significance. RESULTS: Age, gender, and intracranial volume (ICV)-adjusted left thalamic volumes were significantly reduced in CWEOE with cognitive impairment compared to CWEOE without impairment (5295mm3 vs 6418mm3, q=0.008) or healthy controls (5295mm3 vs 6410mm3, q<0.001). The differences in left thalamic volume remained if gray matter or cortical/cerebellar volumes were used as covariates rather than ICV (q<0.05). The degree of volume reduction correlated with the severity of cognitive impairment (q=0.048). SIGNIFICANCE: Reduced left thalamic volume may be a biomarker for cognitive impairment in CWEOE and could help inform the need for further formal cognitive evaluations and interventions.

A case-control study to investigate the prevalence of obstructive sleep apnea and the utility of the PSQ-SRBD questionnaire in children and young people with epilepsy.

STUDY OBJECTIVES: Epilepsy and obstructive sleep apnea syndrome (OSAS) are each relatively common in children. OSAS may affect cognition, such that recognition of OSAS is important for children and young people with epilepsy (CYPWE). Published pilot data reported 55% CYPWE had symptoms suggestive of OSAS, compared with 7% typically developing controls. The primary aim of this study was to ascertain OSAS prevalence by polysomnography (PSG) in CYPWE, with secondary aims being to evaluate the utility of sleep questionnaires in CYPWE. METHODS: Children and young people with epilepsy and age- and sex-matched typically developing controls were studied. A single night of level I attended PSG was undertaken, along with questionnaires [Pediatric Sleep Questionnaire (PSQ-SRBD), Pittsburgh Sleep Quality Index (PSQI) and the childhood and adolescent Epworth Sleepiness Scale (ESS-CHAD)]. OSAS was defined as obstructive apnea-hypopnea index (oAHI) of ≥ 1 event/h. RESULTS: Polysomnography was performed in 72 children including 48 CYPWE (60% male) and 24 controls (54% male). Mean age (11 years) was similar for CYPWE and controls, p= 0.42; with slightly higher BMI z scores (0.7 v 0.1, p=0.03) noted in CYPWE. Mean oAHI was 0.61 in CYPWE versus 0.42 (controls), p=0.62. Despite higher PSQ-SRBD scores in CYPWE (0.38 v 0.12, p<0.001), no difference in OSAS prevalence (10% vs. 4%, p=0.78) was found. Children and young people with epilepsy had higher ESS-CHAD (6 vs. 3.5, p=0.01) and PSQI (5 vs. 3.3, p=0.02) scores indicating greater levels of daytime sleepiness and poorer sleep quality. CONCLUSIONS: The study found no evidence for increased OSAS prevalence in CYPWE, whilst the utility of the PSQ-SRBD in predicting OSAS appears limited for CYPWE. Children and young people with epilepsy are, however demonstrably sleepier with poorer sleep quality. The cause for these findings remains unclear. CLINICAL TRIAL REGISTRATION: Investigation of Sleep Quality and Prevalence of Sleep-disordered Breathing in Children and Young People With Epilepsy; https://www.clinicaltrials.gov/study/NCT03103841.

Incidence of early-onset epilepsy: A prospective population-based study.

PURPOSE: The first five years of life reflect a critical period of development prior to formal education yet few epidemiological studies focus on children with early-onset epilepsy (CWEOE; onset <60 months). This study aimed to determine early-onset epilepsy incidence using a comprehensive case identification strategy, and examined socioeconomic status (SES) and ethnicity as risk factors. METHODS: Through a prospective, population-based study, newly diagnosed CWEOE from Fife and Lothian, Scotland, were identified using multiple-source, active surveillance capture-recapture between May 2013 and June 2015. Crude, ascertainment-adjusted, age-adjusted, age- and gender-specific, and epilepsy-type incidence rates were determined. Risk ratios (RR) were calculated to examine SES and ethnicity as risk factors. RESULTS: 59 (36 Male) CWEOE were identified. Ascertainment was 98% (95% CI 94-103). Crude annual incidence of epilepsy in children 0-59 months was 60.2 (95% CI 44.8-75.5) per 100,000 per year; ascertainment-adjusted annual incidence was 61.7 (95% CI 46.2-77.3) per year. Cumulative incidence of West Syndrome/Infantile Spasms was 6.7 per 10,000 live births (95% CI 3.6-12.3). Aetiology was unknown in almost two-thirds of CWEOE. Compared to White-British Isles (BI) children, Asian children (RR 2.6 [95% CI 1.2-5.7], p = .02) and White-non-BI children (RR 2.5 [95% CI 1.2-5.2], p = .02) had increased risk. SES was not a risk factor. CONCLUSION: The high incidence of early-onset epilepsy is similar to previous studies and demonstrates a substantial disease burden. Cause of epilepsy remains unknown in almost two thirds of CWEOE. Ethnicity but not SES affects early-onset epilepsy risk.

Acute flaccid myelitis caused by enterovirus D68: Case definitions for use in clinical practice.

Acute flaccid myelitis (AFM) was increasingly detected in recent years, coinciding with upsurges of enterovirus D68 (EV-D68) infections. We reviewed the evidence for a causal relationship between both. Based on reported cases, we provide case definitions for AFM caused by EV-D68 infections to enable a standard procedure for affected patients. Current case definitions are focussing on epidemiological aspects but clinical case definitions are still missing. We propose the following case definitions to be used in clinical practice in order to mirror clinical realities and facilitate a common systematic approach in case management: A possible case is defined as a person presenting with either acute myelitis/paralysis or Guillain-Barré Syndrome (GBS), particularly during periods of EV-D68 circulation. A probable case is defined as a person presenting with symptoms of either acute myelitis/paralysis or GBS and at least one of the following criteria: i) MRI abnormality representing with T2 hyperintensity in spinal cord grey matter with or without hyperintensity at dorsal brain stem, ii) investigations showing an axonal neuropathy including reduced compound motor action potentials with normal conduction velocities and absence of conduction blocks compatible with anterior horn cell disease or iii) detection of enteroviruses in a respiratory specimen obtained from the lower respiratory tract during periods of EV-D68 circulation. A confirmed case is defined as a person presenting with acute flaccid myelitis/paralysis, MRI abnormality and detection of enterovirus-D68-specific nucleic acids in a respiratory specimen using a validated PCR assay targeting the VP1 gene with subsequent sequencing and typing.

Industrial Enzymology: The Next Chapter.

This review focuses on recent developments in industrial enzymology, protein engineering, and the design and production of microorganisms. We highlight the latest recombinant DNA (rDNA) technology and tools of protein engineering. These advancements are delivering solutions that address the large unmet needs of customers and markets. To illustrate the progress made over the past three decades, several technological developments and applications are highlighted. High-throughput methods of cell and protein engineering have increased the pace of commercialization. Continuous innovations have impacted many areas of industrial biotechnology and its applications; for example, laundry and dish washing, textile processing, animal health, and human nutrition. The worldwide growth of this bioindustry reflects the potential of biotechnology, which in turn adds a new chapter to the field of industrial enzymology.

Acute Cerebellitis in Children: A Variable Clinical Entity.

Acute cerebellar ataxia is the most common cause of acute ataxia in children and it usually runs a self-limiting and ultimately benign clinical course. A small proportion of children have evidence of inflammatory swelling in the cerebellum. Many of these children suffer more severe and potentially life-threatening forms of cerebellar ataxia and may need more intensive treatments including urgent neurosurgical treatments. This more severe form of acute cerebellar ataxia is often termed acute cerebellitis. Many children with acute cerebellitis have long-term neurological sequela and evidence of structural cerebellar changes on follow-up imaging. Several patterns of cerebellar inflammation have been described. The authors describe the variabilities in the clinical and radiological patterns of disease in the cases that have been described in the literature.