How do children with focal epilepsies perceive the moment they realize that they are about to have a seizure? A pilot study.

PROBLEM: A seizure is a challenging situation for children with epilepsy. Little is known regarding the experience of children who perceive in advance that they are about to have a seizure. METHODS: From September 2020 to February 2021, we invited children with focal epilepsies aged 6-18 years to participate in a semi-structured interview. RESULTS: Of 52 children with focal epilepsies, 22 (42 %) said they perceive in advance that they are about to experience a seizure [11 with self-limited epilepsy with centro-temporal spikes (SELECTs), 11 with other focal epilepsies]. All 22/22 (100 %) children described physical symptoms such as headache or a numb feeling in one half of the body. Of those children, 17/22 (77 %) stated they try to do something about the seizure. Those strategies were perceived as helpful by 0/11 (0 %) children with SELECTs and 9/11 (86 %) children with other focal epilepsies (p < 0.001). Of the children with SELECTs 5/11 (45 %), and of those with other focal epilepsies 9/11 (86 %) stated they would like to know in the morning if they are to experience a seizure that day (n.s.). CONCLUSION: Children who perceive in advance that they are about to have a seizure are well able to describe their experience. Most children take measures to manage their seizures. Those measures were regarded as helpful by most children with other focal epilepsies, but by no child with SELECTs. Larger studies are necessary to determine the factors contributing to the child's perception as well as the nature of the support that they require.

Comorbidities and predictors of health-related quality of life in Dravet syndrome: A 10-year, prospective follow-up study.

OBJECTIVE: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy, leading to reduced health-related quality of life (HRQOL). Prospective outcome data on HRQOL are sparse, and this study investigated long-term predictors of HRQOL in DS. METHODS: One hundred thirteen families of SCN1A-positive patients with DS, who were recruited as part of our 2010 study were contacted at 10-year follow-up, of which 68 (60%) responded. The mortality was 5.8%. Detailed clinical and demographic information was available for each patient. HRQOL was evaluated with two epilepsy-specific instruments, the Impact of Pediatric Epilepsy Scale (IPES) and the Epilepsy & Learning Disabilities Quality of Life Questionnaire (ELDQOL); a generic HRQOL instrument, the Pediatric Quality of Life Inventory (PedsQL); and a behavioral screening tool, the Strength and Difficulties Questionnaire (SDQ). RESULTS: Twenty-eight patients were 10-15 years of age (0-5 years at baseline) and 40 were ≥16 years of age (≥6 years at baseline). Patients 0- to 5-years-old at baseline showed a significant decline in mean scores on the PedsQL total score (p = .004), physical score (p < .001), cognitive score (p = .011), social score (p = .003), and eating score (p = .030) at follow-up. On multivariate regression, lower baseline and follow-up HRQOL for the whole cohort were associated with worse epilepsy severity and a high SDQ total score (R2  = 33% and 18%, respectively). In the younger patient group, younger age at first seizure and increased severity of epilepsy were associated with a lower baseline HRQOL (R2  = 35%). In the older age group, worse epilepsy severity (F = 6.40, p = .016, R2  = 14%) and the use of sodium-channel blockers were independently associated with a lower HRQOL at 10-year follow-up (F = 4.13, p = .05, R2  = 8%). SIGNIFICANCE: This 10-year, prospective follow-up study highlights the significant HRQOL-associated cognitive, social, and physical decline particularly affecting younger patients with DS. Sodium channel blocker use appears to negatively impact long-term HRQOL, highlighting the importance of early diagnosis and disease-specific management in DS.

An estimate of Lyme borreliosis incidence in Western Europe†.

Background: Lyme borreliosis (LB) is the most common zoonotic disease transmitted by ticks in the USA and Europe. This review aims to estimate the regional burden of LB in Western Europe. Data from previous publications will be used to calculate the mean incidence. The mean incidence rates will then be combined to estimate the regional burden and a population-weighted regional burden of disease based on the standardized incidence rate from the included studies and the total population at risk. Methods: Reviews and surveillance reports identified by the initial database search were assessed for eligibility first by their title and abstract and subsequently by a more detailed review of the source by two independent authors for the most recent data regarding LB. Eleven sources of incidence data were included in the review representing 17 countries in total. Incidence estimates were calculated from reported values and population data. Results: Countries in Western Europe have a large variance in the incidence rates. The highest reported incidences for LB were reported in southern Sweden with 464/100 000 and the lowest in Italy of 0.001/100 000. The unweighted mean for the included data provided an incidence rate of 56.3/100 000 persons per year, equating to ∼232 125 cases in 1 year throughout the region. The calculated population-weighted average incidence rate for the regional burden of LB in Western Europe was 22.05 cases per 100 000 person-years. Conclusions: LB is a continually emerging disease and the most common zoonotic infection in Western Europe approaching endemic proportions in many European countries. The population-weighted incidence rate has been estimated by this study to be 22.04/100 000 person-years. Concordant and well-conducted surveillance and disease awareness should continue to be encouraged to monitor LB, as tick numbers and activity are increasing, leading to greater risks of infection.

Long-term predictors of developmental outcome and disease burden in SCN1A-positive Dravet syndrome.

Dravet syndrome is a severe infantile onset developmental and epileptic encephalopathy associated with mutations in the sodium channel alpha 1 subunit gene SCN1A. Prospective data on long-term developmental and clinical outcomes are limited; this study seeks to evaluate the clinical course of Dravet syndrome over a 10-year period and identify predictors of developmental outcome. SCN1A mutation-positive Dravet syndrome patients were prospectively followed up in the UK from 2010 to 2020. Caregivers completed structured questionnaires on clinical features and disease burden; the Epilepsy & Learning Disability Quality of Life Questionnaire, the Adaptive Behavioural Assessment System-3 and the Sleep Disturbance Scale for Children. Sixty-eight of 113 caregivers (60%) returned posted questionnaires. Developmental outcome worsened at follow-up (4.45 [SD 0.65], profound cognitive impairment) compared to baseline (2.9 [SD 1.1], moderate cognitive impairment, P < 0.001), whereas epilepsy severity appeared less severe at 10-year follow-up (P = 0.042). Comorbidities were more apparent at 10-year outcome including an increase in autistic features (77% [48/62] versus 30% [17/57], χ2 = 19.9, P < 0.001), behavioural problems (81% [46/57] versus 38% [23/60], χ2 = 14.1, P < 0.001) and motor/mobility problems (80% [51/64] versus 41% [24/59], χ2 = 16.9, P < 0.001). Subgroup analysis demonstrated a more significant rise in comorbidities in younger compared to older patients. Predictors of worse long-term developmental outcome included poorer baseline language ability (P < 0.001), more severe baseline epilepsy severity (P = 0.003) and a worse SCN1A genetic score (P = 0.027). Sudden unexpected death in epilepsy had not been discussed with a medical professional in 35% (24/68) of participants. Over 90% of caregivers reported a negative impact on their own health and career opportunities. Our study identifies important predictors and potential biomarkers of developmental outcome in Dravet syndrome and emphasizes the significant caregiver burden of illness. The negative impact of epilepsy severity at baseline on long-term developmental outcomes highlights the importance of implementing early and focused therapies whilst the potential impact of newer anti-seizure medications requires further study.

Paediatric inflammatory multisystem syndrome temporally associated with COVID-19: a new virus and a new case presentation.

An 11-year-old boy presented with features resembling those described in health alerts on Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS), including persistent fever, haemodynamic instability and abdominal pain. Laboratory tests, including raised inflammatory markers, D-dimer, troponin and a coagulopathy, were consistent with PIMS-TS. Our patient required transfer to the paediatric intensive care unit; an echocardiography revealed left ventricular dysfunction. He was treated with intravenous immunoglobulins (Igs), corticosteroids and aspirin, with full resolution of clinical symptoms. A follow-up echocardiogram 1 month after discharge was unremarkable.Three SARS-CoV-2 PCRs on respiratory samples, taken over the initial 4-day period, were negative, as was a SARS-CoV-2 PCR on faeces 1 month after presentation; titres of IgG were clearly elevated. The negative PCRs in the presence of elevated titres of IgG suggest that the inflammatory syndrome might have developed in a late phase of COVID-19 infection when the virus was no longer detectable in the upper airway.

[Relapsing fever after travelling in the tropics; a story with a twist]. / Terugkerende koorts na een reis in de tropen.

BACKGROUND: Relapsing fever is an infectious disease caused by Spirochaetes. The presentation is characterised by recurrent episodes of fever. CASE DESCRIPTION: At the end of her trip through South Africa and Botswana, a 54-year-old woman had symptoms of fever and dry cough. Back in the Netherlands, physical examination at the emergency department did not reveal any abnormalities besides fever. Laboratory investigation found thrombocytopenia and elevated infection markers. Thick blood smear revealed the presence of Spirochaetes. Following a working diagnosis of 'relapsing fever', the patient was treated with doxycycline. There was no Jarisch-Herxheimer reaction. At a follow-up outpatient appointment two weeks later, the patient had fully recovered. CONCLUSION: Relapsing fever is a rare disease without specific symptoms. The diagnosis is therefore easily overlooked. Untreated, mortality is high. During episodes of fever, the diagnosis can be established with a thick blood smear.

Recommendations for enterovirus diagnostics and characterisation within and beyond Europe.

Enteroviruses (EV) can cause severe neurological and respiratory infections, and occasionally lead to devastating outbreaks as previously demonstrated with EV-A71 and EV-D68 in Europe. However, these infections are still often underdiagnosed and EV typing data is not currently collected at European level. In order to improve EV diagnostics, collate data on severe EV infections and monitor the circulation of EV types, we have established European non-polio enterovirus network (ENPEN). First task of this cross-border network has been to ensure prompt and adequate diagnosis of these infections in Europe, and hence we present recommendations for non-polio EV detection and typing based on the consensus view of this multidisciplinary team including experts from over 20 European countries. We recommend that respiratory and stool samples in addition to cerebrospinal fluid (CSF) and blood samples are submitted for EV testing from patients with suspected neurological infections. This is vital since viruses like EV-D68 are rarely detectable in CSF or stool samples. Furthermore, reverse transcriptase PCR (RT-PCR) targeting the 5'noncoding regions (5'NCR) should be used for diagnosis of EVs due to their sensitivity, specificity and short turnaround time. Sequencing of the VP1 capsid protein gene is recommended for EV typing; EV typing cannot be based on the 5'NCR sequences due to frequent recombination events and should not rely on virus isolation. Effective and standardized laboratory diagnostics and characterisation of circulating virus strains are the first step towards effective and continuous surveillance activities, which in turn will be used to provide better estimation on EV disease burden.