- Email: [email protected]
Febrile seizures and risk of death
Comment
8
9
10
Ng R, Pond GR, Tang PA, et al. Correlation of changes between 2-year disease-free survival and 5-year overall survival in adjuvant breast cancer trials from 1966–2006. Ann Oncol 2008; 19: 482–86. Bukowski RM, Eisen T, Szczylik C, et al. Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: survival and biomarker analysis. J Clin Oncol 2007; 25 (suppl 18): 5023 (abstr). Figlin RA, Hutson TE, Tomczac P, et al. Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC). J Clin Oncol 2008; 26 (suppl May 20): 5024 (abstr).
11 12
13
Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal cell carcinoma. N Engl J Med 2007; 356: 2271–81. Escudier B, Pluzanska A, Korlewski P, et al, for the AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007; 370: 2103–11. Negrier S, Perol D, Ravaud A, et al. Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic RCC of intermediate prognosis. Cancer 2007; 110: 2468–77.
Febrile seizures and risk of death
www.thelancet.com Vol 372 August 9, 2008
temperatures, possibly reflecting that the same agent leads to seizure in older children and death in infants. The shared susceptibility hypothesis had little support, however, from large epidemiological studies that showed sudden infant death syndrome (SIDS) and febrile seizures occur in different populations. SIDS is more frequent in African-American children, for example,7–9 whereas this higher risk is not mirrored in febrile seizures.10 SIDS and febrile seizures do not seem to occur together in families.11 The idea of a shared cause between sudden death and febrile seizures was renewed by Kinney and colleagues,12 who showed developmental hippocampal changes in five toddlers who died suddenly. Of these five, one had a history of febrile seizures, one had a family history of febrile seizures, and one had both febrile seizures and a positive family history. The investigators speculated that the cause of death for these toddlers might be seizures during sleep. Their results were intriguing, but given the small sample and the high prevalence of febrile seizures
See Articles page 457
Science Photo Library
In today’s Lancet, Mogens Vestergaard and colleagues investigate the relation between febrile seizures and death, using data from nationwide registries in Denmark.1 A febrile seizure is defined as a seizure occurring during a febrile illness—excluding intracranial infection or inflammation—in a child between the ages of 3 months and 5 years who has not had a previous seizure in the absence of fever.2 A febrile seizure is called simple if the seizure is brief (less than 15 min), generalised, and does not recur during the same febrile illness. By contrast, a febrile seizure is called complex if there are focal features, long duration, or recurrence within 24 h. The outcome of febrile seizures is usually favourable, and changes in management of febrile seizures over the past few decades have reflected the generally good prognosis. Parental reassurance has replaced aggressive diagnostic workup and anticonvulsant therapy. Between 2% and 4% of children with febrile seizures go on to have epilepsy, which is defined as recurrent unprovoked seizures. Risk factors for the development of epilepsy include complex features of the initial attack and underlying neurodevelopmental abnormality.3 Younger age at onset and family history can also indicate a higher risk of recurrent seizures.4 Despite the general acceptance that children with febrile seizures have a good prognosis, the hypothesis persists that febrile seizures are linked aetiologically to sudden death in infants and children through a common infectious or environmental agent, anatomical abnormality, or genetic susceptibility to fever. This hypothesis came from experiments in kittens5 and found some support in a 1981 Lancet study6 that compared the ages and presenting temperatures of children with cot deaths and those with febrile seizures in a large population of children in Sheffield, UK. This study found that the children who died were younger than those with febrile seizures and many of them had high
429
Comment
in the general population, it is difficult to exclude chance as an explanation for their findings. In today’s study, Vestergaard and colleagues tested the hypothesis that febrile seizures are associated with an increased risk of death, by examining mortality data from a cohort of more than 1·6 million children, including over 55 000 children with febrile seizures and over 8000 deaths. They noted that in children who had a febrile seizure, there was an increased risk of death in the 2 years after the first febrile seizure, but that the absolute risk of death was still very low. In a nested case-control study, they attempted to find more clinical information than is usually available in registry data, through review of medical records. They report that the increased risk of death after febrile seizure was seen only in children with complex febrile seizures and in those with underlying neurological abnormalities. Vestergaard and colleagues’ study again seems to refute, for infants and children who have simple febrile seizures, the idea of a shared cause between febrile seizures and sudden death. Similar to previous studies, most recently that of Kinney and colleagues, the new study suggests there is a subset of children with febrile seizures—notably those with complex features and underlying neurological abnormalities—that might warrant closer attention and follow-up.
Maitreyi Mazumdar Department of Neurology, Children’s Hospital Boston, Boston, MA 02115, USA [email protected] I declare that I have no conflict of interest. 1
2 3 4
5
6 7 8
9 10 11
12
Vestergaard M, Giørtz Pedersen M, Østergaard JR, Bøcker Pedersen C, Olsen J, Christensen J. Death in children with febrile seizures: a populationbased cohort study. Lancet 2008; 372: 457–63. Consensus development conference on febrile seizures, National Institutes of Health, May 19–21, 1980. Epilepsia 1981; 22: 377–81. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med 1976; 295: 1029–33. Offringa M, Bossuyt PM, Lubsen J, et al. Risk factors for seizure recurrence in children with febrile seizures: a pooled analysis of individual patient data from five studies. J Pediatr 1994; 124: 574–84. Lennox MA, Sibley WA, Zimmerman HM. Fever and febrile convulsions in kittens: a clinical, electroencephalographic, and histopathologic study. J Pediatr 1954; 45: 179–90. Sunderland R, Emery JL. Febrile convulsions and cot death. Lancet 1981; 2: 176–78. Hoyert DL, Arias E, Smith BL, Murphy SL, Kochanek KD. Deaths: final data for 1999. Natl Vital Stat Rep 2001; 49: 1–113. Mathews TJ, Menacker F, MacDorman MF. Infant mortality statistics from the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep 2004; 53: 1–29. Moon RY, Horne RS, Hauck FR. Sudden infant death syndrome. Lancet 2007; 370: 1578–87. Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures. Pediatrics 1978; 61: 720–27. Vestergaard M, Basso O, Henriksen TB, Ostergaard J, Olsen J. Febrile convulsions and sudden infant death syndrome. Arch Dis Child 2002; 86: 125–26. Kinney H, Armstrong D, Chadwick A, et al. Sudden death in toddlers associated with developmental abnormalities of the hippocampus: a report of five cases. Pediatr Dev Pathol 2007; 10: 208–23.
The rising tide of dementia worldwide Published Online July 28, 2008 DOI:10.1016/S01406736(08)61003-X See Articles page 464
430
Our grasp of the personal and public-health challenges that dementia poses worldwide keeps evolving. A major step is reported in today’s Lancet by Juan Llibre Rodriguez and colleagues from the 10/66 Dementia Research Group in a population-based study.1 Less than 40 years ago, Alzheimer’s disease was lumped with Pick’s disease as a presenile dementia; and cognitive decline, including extreme senility, was supposedly part of a continuum of normal ageing. That view became untenable when the numbers of elderly people in developed countries mushroomed. Dementias occur mainly in old people, doubling in prevalence about every 5 years after 65 years of age in developed countries2 and every 7 years in developing ones. More recently, dementia research has posited mild cognitive impairment, a curious and heterogeneous condition. Some call it a disease, but others say that
makes it into a process that can be part of normal ageing. Mild cognitive impairment is common in elderly people and affects nearly one in four older than 70 years of age.3 The condition does not necessarily lead to dementia. By itself, it characteristically causes no substantial dysfunction, other than subjective worry. Llibre Rodriguez and colleagues studied rates of dementia in elderly people in low-income and middleincome countries. They found that the rates of dementia varied widely between nations but tended to be higher than previously thought; and rates in urban Latin America (approaching 10%) resemble those in high-income countries. Populations worldwide are increasingly ageing, so late-life dementias have far-reaching consequences for health. Dementia is rare in people younger than 65 years of age, but incidence increases exponentially with age, www.thelancet.com Vol 372 August 9, 2008
8
9
10
Ng R, Pond GR, Tang PA, et al. Correlation of changes between 2-year disease-free survival and 5-year overall survival in adjuvant breast cancer trials from 1966–2006. Ann Oncol 2008; 19: 482–86. Bukowski RM, Eisen T, Szczylik C, et al. Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: survival and biomarker analysis. J Clin Oncol 2007; 25 (suppl 18): 5023 (abstr). Figlin RA, Hutson TE, Tomczac P, et al. Overall survival with sunitinib versus interferon (IFN)-alfa as first-line treatment of metastatic renal cell carcinoma (mRCC). J Clin Oncol 2008; 26 (suppl May 20): 5024 (abstr).
11 12
13
Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal cell carcinoma. N Engl J Med 2007; 356: 2271–81. Escudier B, Pluzanska A, Korlewski P, et al, for the AVOREN Trial investigators. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet 2007; 370: 2103–11. Negrier S, Perol D, Ravaud A, et al. Medroxyprogesterone, interferon alfa-2a, interleukin 2, or combination of both cytokines in patients with metastatic RCC of intermediate prognosis. Cancer 2007; 110: 2468–77.
Febrile seizures and risk of death
www.thelancet.com Vol 372 August 9, 2008
temperatures, possibly reflecting that the same agent leads to seizure in older children and death in infants. The shared susceptibility hypothesis had little support, however, from large epidemiological studies that showed sudden infant death syndrome (SIDS) and febrile seizures occur in different populations. SIDS is more frequent in African-American children, for example,7–9 whereas this higher risk is not mirrored in febrile seizures.10 SIDS and febrile seizures do not seem to occur together in families.11 The idea of a shared cause between sudden death and febrile seizures was renewed by Kinney and colleagues,12 who showed developmental hippocampal changes in five toddlers who died suddenly. Of these five, one had a history of febrile seizures, one had a family history of febrile seizures, and one had both febrile seizures and a positive family history. The investigators speculated that the cause of death for these toddlers might be seizures during sleep. Their results were intriguing, but given the small sample and the high prevalence of febrile seizures
See Articles page 457
Science Photo Library
In today’s Lancet, Mogens Vestergaard and colleagues investigate the relation between febrile seizures and death, using data from nationwide registries in Denmark.1 A febrile seizure is defined as a seizure occurring during a febrile illness—excluding intracranial infection or inflammation—in a child between the ages of 3 months and 5 years who has not had a previous seizure in the absence of fever.2 A febrile seizure is called simple if the seizure is brief (less than 15 min), generalised, and does not recur during the same febrile illness. By contrast, a febrile seizure is called complex if there are focal features, long duration, or recurrence within 24 h. The outcome of febrile seizures is usually favourable, and changes in management of febrile seizures over the past few decades have reflected the generally good prognosis. Parental reassurance has replaced aggressive diagnostic workup and anticonvulsant therapy. Between 2% and 4% of children with febrile seizures go on to have epilepsy, which is defined as recurrent unprovoked seizures. Risk factors for the development of epilepsy include complex features of the initial attack and underlying neurodevelopmental abnormality.3 Younger age at onset and family history can also indicate a higher risk of recurrent seizures.4 Despite the general acceptance that children with febrile seizures have a good prognosis, the hypothesis persists that febrile seizures are linked aetiologically to sudden death in infants and children through a common infectious or environmental agent, anatomical abnormality, or genetic susceptibility to fever. This hypothesis came from experiments in kittens5 and found some support in a 1981 Lancet study6 that compared the ages and presenting temperatures of children with cot deaths and those with febrile seizures in a large population of children in Sheffield, UK. This study found that the children who died were younger than those with febrile seizures and many of them had high
429
Comment
in the general population, it is difficult to exclude chance as an explanation for their findings. In today’s study, Vestergaard and colleagues tested the hypothesis that febrile seizures are associated with an increased risk of death, by examining mortality data from a cohort of more than 1·6 million children, including over 55 000 children with febrile seizures and over 8000 deaths. They noted that in children who had a febrile seizure, there was an increased risk of death in the 2 years after the first febrile seizure, but that the absolute risk of death was still very low. In a nested case-control study, they attempted to find more clinical information than is usually available in registry data, through review of medical records. They report that the increased risk of death after febrile seizure was seen only in children with complex febrile seizures and in those with underlying neurological abnormalities. Vestergaard and colleagues’ study again seems to refute, for infants and children who have simple febrile seizures, the idea of a shared cause between febrile seizures and sudden death. Similar to previous studies, most recently that of Kinney and colleagues, the new study suggests there is a subset of children with febrile seizures—notably those with complex features and underlying neurological abnormalities—that might warrant closer attention and follow-up.
Maitreyi Mazumdar Department of Neurology, Children’s Hospital Boston, Boston, MA 02115, USA [email protected] I declare that I have no conflict of interest. 1
2 3 4
5
6 7 8
9 10 11
12
Vestergaard M, Giørtz Pedersen M, Østergaard JR, Bøcker Pedersen C, Olsen J, Christensen J. Death in children with febrile seizures: a populationbased cohort study. Lancet 2008; 372: 457–63. Consensus development conference on febrile seizures, National Institutes of Health, May 19–21, 1980. Epilepsia 1981; 22: 377–81. Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med 1976; 295: 1029–33. Offringa M, Bossuyt PM, Lubsen J, et al. Risk factors for seizure recurrence in children with febrile seizures: a pooled analysis of individual patient data from five studies. J Pediatr 1994; 124: 574–84. Lennox MA, Sibley WA, Zimmerman HM. Fever and febrile convulsions in kittens: a clinical, electroencephalographic, and histopathologic study. J Pediatr 1954; 45: 179–90. Sunderland R, Emery JL. Febrile convulsions and cot death. Lancet 1981; 2: 176–78. Hoyert DL, Arias E, Smith BL, Murphy SL, Kochanek KD. Deaths: final data for 1999. Natl Vital Stat Rep 2001; 49: 1–113. Mathews TJ, Menacker F, MacDorman MF. Infant mortality statistics from the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep 2004; 53: 1–29. Moon RY, Horne RS, Hauck FR. Sudden infant death syndrome. Lancet 2007; 370: 1578–87. Nelson KB, Ellenberg JH. Prognosis in children with febrile seizures. Pediatrics 1978; 61: 720–27. Vestergaard M, Basso O, Henriksen TB, Ostergaard J, Olsen J. Febrile convulsions and sudden infant death syndrome. Arch Dis Child 2002; 86: 125–26. Kinney H, Armstrong D, Chadwick A, et al. Sudden death in toddlers associated with developmental abnormalities of the hippocampus: a report of five cases. Pediatr Dev Pathol 2007; 10: 208–23.
The rising tide of dementia worldwide Published Online July 28, 2008 DOI:10.1016/S01406736(08)61003-X See Articles page 464
430
Our grasp of the personal and public-health challenges that dementia poses worldwide keeps evolving. A major step is reported in today’s Lancet by Juan Llibre Rodriguez and colleagues from the 10/66 Dementia Research Group in a population-based study.1 Less than 40 years ago, Alzheimer’s disease was lumped with Pick’s disease as a presenile dementia; and cognitive decline, including extreme senility, was supposedly part of a continuum of normal ageing. That view became untenable when the numbers of elderly people in developed countries mushroomed. Dementias occur mainly in old people, doubling in prevalence about every 5 years after 65 years of age in developed countries2 and every 7 years in developing ones. More recently, dementia research has posited mild cognitive impairment, a curious and heterogeneous condition. Some call it a disease, but others say that
makes it into a process that can be part of normal ageing. Mild cognitive impairment is common in elderly people and affects nearly one in four older than 70 years of age.3 The condition does not necessarily lead to dementia. By itself, it characteristically causes no substantial dysfunction, other than subjective worry. Llibre Rodriguez and colleagues studied rates of dementia in elderly people in low-income and middleincome countries. They found that the rates of dementia varied widely between nations but tended to be higher than previously thought; and rates in urban Latin America (approaching 10%) resemble those in high-income countries. Populations worldwide are increasingly ageing, so late-life dementias have far-reaching consequences for health. Dementia is rare in people younger than 65 years of age, but incidence increases exponentially with age, www.thelancet.com Vol 372 August 9, 2008