Update on Sudden Unexpected Death in Epilepsy.

Persons with epilepsy (PWE) have an up to 34-fold increased risk of dying suddenly and unexpectedly compared with the general population. Despite being potentially preventable by optimal care, sudden unexpected death in epilepsy (SUDEP) is one of the most frequent causes of death in PWE, especially in children and younger adults. The incidence of SUDEP in the general epilepsy population is rather consistent at 1.2 to 1.3 per 1000 person-year across series. Several risk factors for SUDEP have been identified, but with focal-to-bilateral or generalized tonic-clonic seizures and sleeping alone as the most significant. Thereby, optimal care and nocturnal surveillance might decrease the risk of SUDEP. Finally, PWE wants information about SUDEP, and providing this information might increase adherence to the treatment and thereby good seizure control. This narrative review provides an update on SUDEP.

[Sudden unexpected death in epilepsy].

Sudden and unexpected death is defined as sudden death without any obvious cause and where the person was seen in habitual conditions within the last 24 hours before death. Persons with epilepsy have a 34-fold increased risk of dying suddenly and unexpectedly compared with the background population. In persons with epilepsy these deaths are referred to as sudden unexpected death in epilepsy (SUDEP). This review finds that the risk is highest in younger adults, and SUDEP is the second leading cause of death in persons with epilepsy aged 1-49 years. Good seizure control is important in the prevention of SUDEP.

[Basic and advanced treatment of children and adults with epilepsy].

This review finds that, in children and adults with epilepsy, there are several treatment options. Multiple antiseizure medications are available and in case of drug-resistant epilepsy, a non-pharmacological approach is recommended, including epilepsy surgery, vagus nerve stimulation, or ketogenic diet treatment. The aim of the treatment is to avoid further seizures, but also to avoid negative cognitive, psychological, and social consequences of epilepsy.

Epilepsy-Related Mortality in Children and Young Adults in Denmark: A Nationwide Cohort Study.

BACKGROUND AND OBJECTIVES: Mortality is increased in epilepsy, but the important issue is that a proportion of epilepsy-related death is potentially preventable by optimized therapy and therefore needs to be identified. A new systematic classification of epilepsy-related mortality has been suggested to identify these preventable deaths. We applied this classification to an analysis of premature mortality in persons with epilepsy who were <50 years of age. METHODS: The study was a population-based retrospective cohort of all Danish citizens with and without epilepsy 1 to 49 years of age during 2007 to 2009. Information on all deaths was retrieved from the Danish Cause of Death Registry, autopsy reports, death certificates, and the Danish National Patient Registry. The primary cause of death in persons with epilepsy was evaluated independently by 3 neurologist, 1 neuro-pediatrician, and 2 cardiologists. In case of uncertainty, a pathologist was consulted. All deaths were classified as either epilepsy related or not epilepsy related, and the underlying causes or modes of death were compared between persons with and without epilepsy. RESULTS: During the study period, 700 deaths were identified in persons with epilepsy, and 440 (62.9%) of these were epilepsy related, 169 (38%) directly related to seizures and 181 (41%) due to an underlying neurologic disease. Sudden unexpected death in epilepsy accounted for 80% of deaths directly related to epilepsy. Aspiration pneumonia was the cause of death in 80% of cases indirectly related to epilepsy. Compared with the background population, persons with epilepsy had a nearly 4-fold increased all-cause mortality (adjusted mortality hazard ratio 3.95 [95% confidence interval [CI] 3.64-4.27], p < 0.0001) and a higher risk of dying of various underlying causes, including alcohol-related conditions (hazard ratio 2.91 [95% CI 2.23-3.80], p < 0.0001) and suicide (hazard ratio 2.10 [95% CI 1.18-3.73], p = 0.01). DISCUSSION: The newly proposed classification for mortality in persons with epilepsy was useful in an unselected nationwide cohort. It helped in classifying unnatural causes of death as epilepsy related or not and in identifying potentially preventable deaths. The leading causes of premature mortality in persons <50 years of age were related to epilepsy and were thus potentially preventable by good seizure control.

Comparing Seizure-Related Death and Suicide in Younger Adults with Epilepsy.

Younger adults with epilepsy have an increased mortality. Some deaths are seizure-related, for example, sudden unexpected death in epilepsy (SUDEP), whereas others, for example, suicide, have multiple causes, including adverse effects of the treatment on mood. In this retrospective population-based study of all Danish persons with epilepsy aged 18 to 49 years during 2007 to 2009 we evaluated the risk of death from seizures and suicide. SUDEP comprised 82.7% of all seizure-related death. Younger adults with epilepsy had an 8.3-fold increased risk of death from seizure-related causes compared with suicide. This underpins the importance of effective seizure control in preventing premature death. ANN NEUROL 2021;90:983-987.

Sudden unexpected death in epilepsy in persons younger than 50 years: A retrospective nationwide cohort study in Denmark.

OBJECTIVE: Persons with epilepsy have an increased mortality including a high risk of sudden unexplained death (SUD), also referred to as sudden unexpected death in epilepsy (SUDEP). We aimed to evaluate the risk of SUDEP in comparison to other causes of death and the risk of SUD in persons with and without epilepsy. METHODS: We undertook a retrospective population-based cohort study of all Danish citizens with and without epilepsy aged 1-49 years during 2007-2009. All deaths in the population were evaluated, and all cases of SUD identified. Primary causes of death in persons with epilepsy were evaluated independently by three neurologists and one neuropediatrician, using the unified SUDEP criteria. RESULTS: The three most frequent causes of death in persons with epilepsy were cancer (2.38 per 1000 person-years), SUDEP (1.65 per 1000 person-years), and pneumonia (1.09 per 1000 person-years) compared with cancer (.17 per 1000 person-years), accident-related deaths (.14 per 1000 person-years), and cardiovascular disease (.09 per 1000 person-years) in persons without epilepsy. Considering definite, definite plus, and probable cases, the SUDEP incidence was .27 per 1000 person-years (95% confidence interval [CI] = .11-.64) in children aged 1-17 years and 1.21 per 1000 person-years (95% CI = .96-1.51) in adults aged 18-49 years. Adjusted for age and sex, persons with epilepsy younger than 50 years had a 10.8-fold (95% CI = 9.97-11.64, p < .0001) increased all-cause mortality and a 34.4-fold (95% CI = 23.57-50.28, p < .0001) increased risk of SUD compared with persons without epilepsy. SUDEP accounted for 23.3% of all SUD. SIGNIFICANCE: This nationwide study of all deaths in persons with epilepsy younger than 50 years found a lower SUDEP risk in children compared with adults, and that epilepsy was a major risk factor for SUD in the background population. This underlines the importance of addressing risk factors for SUDEP to prevent premature death.

Deciphering the premature mortality in PIGA-CDG - An untold story.

OBJECTIVE: Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have suggested that patients with PIGA-CDG have a high risk of premature mortality. This study aimed to evaluate the observed high mortality and the causes of death in PIGA-CDG patients. METHODS: We reviewed the literature and collected additional unpublished patients through an international network. RESULTS: In total, we reviewed the data of 88 patients of whom 30 patients born alive were deceased, and the overall mortality before the age of 20 years was 30 % (26/88). Age at death ranged from 15 days to 48 years of life. The median age at death was two years and more than half of the patients deceased in early childhood. The PIGA-specific mortality rate/1000 person-years was 44.9/1000 person-years (95 %, CI 31.4-64.3). There were no cases of definite or probable sudden unexpected death in epilepsy (SUDEP) and half of the patients died due to respiratory failure (15/30, 50 %) or possible SUDEP (3/30, 10 %). Three patients (10 %) died from severe cardiomyopathy, liver failure and gastrointestinal bleeding, respectively. The cause of death was unclassified in nine patients (30 %). Autopsies were rarely performed and the true cause of death remains unknown for the majority of patients. SIGNIFICANCE: Our data indicate an increased risk of premature death in patients with PIGA-CDG when compared to most monogenic developmental and epileptic encephalopathies.

Growth of children in Greenland exceeds the World Health Organization growth charts.

AIM: Previous studies have found high rates of stunted linear growth in Greenlandic children. We measured growth patterns in Greenland and compared them with international growth charts. METHODS: The study cohort comprised 279 healthy children aged 6-10 years in 2012. They participated in two pregnancy and birth cohorts in Greenland and longitudinal growth data as birth was extracted from their medical records. Growth reference ranges were estimated with the lambda-mu-sigma (LMS) method and compared with growth charts from Denmark and the World Health Organization (WHO). RESULTS: The children's mean length, weight and head circumference were significantly larger than the WHO growth charts (p < 0.001). We found that 21-28% of the children aged zero to one years exceeded the WHO growth chart for length by more than two standard deviations. For weight and head circumference, 9-16% of the children aged 0-10 years and 9-11% of the children from zero to two years exceeded the WHO charts by more than two standard deviations. The Danish references were exceeded to a lesser degree. CONCLUSION: This study showed that the growth of Greenlandic children up to 10 years was no longer stunted. Major determining factors suggested are genetic admixture, maternal overweight, changes in nutrition and improved health.

Children in Greenland: disease patterns and contacts to the health care system.

BACKGROUND: Previous studies of Greenlandic children's disease pattern and contacts to the health care system are sparse and have focused on the primary health care sector. OBJECTIVE: We aimed to identify the disease pattern and use of health care facilities of children aged 0-10 in two Greenlandic cohorts. METHODS AND DESIGN: In a retrospective, descriptive follow-up of the Ivaaq (The Greenland Child Cohort) and the CLEAR (climate changes, environmental contaminants and reproductive health) birth cohorts (total n=1,000), we reviewed medical records of children aged 6-10 in 2012 with residence in Nuuk or Ilulissat (n=332). Data on diseases and health care system contacts were extracted. Diagnoses were validated retrospectively. Primary health care contacts were reviewed for a random sample of 1:6. RESULTS: In 311 children with valid social security number, the total number of health care system contacts was 12,471 equalling 4.6 contacts per child per year. The annual incidence rate of hospital admissions was 1:10 children (total n=266, 1,220 days, 4.6 days/admission), outpatient contacts 2:10 children and primary care 3.6 per child. Contacts were overall more frequent in boys compared with girls, 39.5 versus 34.6 during the study period, p=0.02. The highest annual contact rates for diseases were: hospitalisations/acute respiratory diseases 13.9:1,000; outpatient contacts/otitis media 5.1:1,000; primary care/conjunctivitis or nasopharyngitis 410:1,000 children. Outpatient screening for respiratory tuberculosis accounted 6.2:1,000, primary care non-disease (Z-diagnosis) 2,081:1,000 annually. Complete adherence to the child vaccination programme was seen in 40%, while 5% did not receive any vaccinations. CONCLUSIONS: In this first study of its kind, the health care contact pattern in Greenlandic children showed a relatively high hospitalisation rate and duration per admission, and a low primary health care contact rate. The overall contact rate and disease pattern resembled those in Denmark, except for tuberculosis screening. Adherence to the vaccination programme was low. These findings may be helpful for the organisation and dimensioning of the Greenlandic health care system for children.

[Atypical presentation of tuberous sclerosis].

Tuberous sclerosis complex (TSC) is an inherited disorder with a prevalence of 1/20,000. The diagnosis is based on clinical criteria and/or genetic testing. Most cases are found during childhood. Yet, the intra- and interfamiliar expressivity is variable, so the diagnosis should be considered in adults too. This is a case report about a 20-year-old female with an atypical presentation of TSC. The case highlights that TSC can be suspected in adults with a first-time seizure. The diagnosis is important because it leads to multidisciplinary follow-up.