- Email: [email protected]
Life expectancy in epilepsy
Comment
could lead to use of treatments that lower albumin in the urine and improve renal and cardiac prognosis and reduce the risk of developing diabetic renal disease. Such a screening campaign and primary preventive intervention is feasible.11,12 A consensus of the Amsterdam meeting was presented to the Chief Medical Officer of Europe, Herre Kingma, who promised to take this further to his European colleagues. In the Netherlands, Kingma is considering the possibility to complement the traditional health-screening centres for infants and young children, currently used for monitoring general health and providing vaccinations, with a similar function for adults aimed at early detection and prevention of chronic diseases, for which measurement of albuminuria could be one of the variables to monitor. The ISN is particularly committed to promote the implementation of preventive strategies for kidney and generalised vascular diseases in developing countries. In the mid-1990s, ISN created the Commission for the Global Advancement of Nephrology (COMGAN), with the aim to provide educational programmes for developing countries through teaching programmes, fellowship and visiting scholar programmes, and travel grants. COMGAN’s activities have grown to include programmes aimed to assess research needs, opportunities, and implementation strategies in developing countries and identify the necessary resources required. ISN is willing to promote and support collaborations with health-care authorities and local as well as international scientific societies to identify needs and design specific screening and intervention strategies.
Giuseppe Remuzzi, *Jan J Weening Mario Negri Institute for Pharmacological Research,
Laboratori Negri Bergamo, Bergamo, Italy (GR); and Academic Medical Centre, University of Amsterdam, Department of Pathology, 1105 AZ Amsterdam, Netherlands (JJW) [email protected] GR is chair of ISN COMGAN’s Research Committee and JJW is President of ISN, and both were involved in the organisation of some of the meetings mentioned above. 1
2
3
4 5 6 7
8
9
10
11
12
Xue JL, Ma JZ, Louis TA, Collins AJ. Forecast of the number of patients with end-stage renal disease in the United States to the year 2010. J Am Soc Nephrol 2001; 12: 2753–58. Wild SH, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030: response to Rathman and Giani. Diabetes Care 2004; 27: 2569–70. Moeller S, Gioberge S, Brown G. ESRD patients in 2001: global overview of patients, treatment modalities and development trends. Nephrol Dial Transplant 2002; 17: 2071–76. Lysaght MJ. Maintenance dialysis population dynamics: current trends and long-term implications. J Am Soc Nephrol 2002; 13 (suppl 1): S37–40. Barsoum RS. Overview: end-stage renal disease in the developing world. Artif Organs 2002; 26: 737–46. Brenner BM. Retarding the progression of renal disease. Kidney Int 2003; 64: 370–78. Brenner BM, Zagrobelny J. Clinical renoprotection trials involving angiotensin II-receptor antagonists and angiotensin-converting-enzyme inhibitors. Kidney Int Suppl 2003; Feb: S77–85. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–63. Brenner BM, Cooper ME, de Zeeuw D, for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–69. Hillege HL, Fidler V, Diercks GF, for the Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106: 1777–82. Ruggenenti P, Fassi A, Ilieva AP, for the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004; 351: 1941–51. Verhave JC, Gansevoort RT, Hillege HL, for the PREVEND Study Group. An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. Kidney Int Suppl 2004; Nov: S18–21.
Life expectancy in epilepsy Does a diagnosis of epilepsy reduce a person’s life expectancy? According to Athanasios Gaitatzis and colleagues the answer is yes, but under certain circumstances and to a variable extent.1 These authors recently estimated life expectancy in people with epilepsy, with data from the prospective community-based UK National General Practice Study of Epilepsy (NGPSE),2 and made comparisons with the general population. Life expectancy can be reduced by up to 10 years when there is a known cause of the epilepsy, the estimated reduction being highest at the time of diagnosis. These observations are hardly surprising considering the wealth of literature that shows increased mortality rates in people with epilepsy. Traditionally, mortality has been expressed as the ratio of the observed and expected numbers of death: the standardised mortality ratio. Expected deaths are calculated by www.thelancet.com Vol 365 February 12, 2005
applying the death rates of an external reference population to the age distribution of the study population. The epilepsy population has an standardised mortality ratio of 2–3 (ie, a mortality that is 2–3 times higher than that of the general population).3–8 People with epilepsy of unknown cause have at most only a slight increase in mortality, while those with epilepsy as a symptom of a known underlying cause largely account for the overall increased mortality. The increase is evident during the first years after the onset of epilepsy, and mortality then declines to levels close to those in the general population. However, some studies show an increase in mortality later, a decade or more after disease onset.4,8 Relative survivorship, defined as the proportion of observed to expected number of survivors, provides a different perspective of mortality. The relative survivorship at 5, 10, and 15 years after diagnosis was 91%, 557
Comment
Science Photo Library
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
85% and 83%, respectively, in a pioneering study.9 In epilepsy of unknown cause relative survivorship is as high as 96% 25 years after diagnosis.6 Gaitatzis and colleagues introduce yet another way of analysing data on mortality in patients with epilepsy. The estimated life expectancy of people with new-onset nonfebrile seizures from the UK followed up for a median of 15 years was compared with that in people of the same age and sex in the general population. The difference in life expectancy between these populations gives the estimated years of life lost, which is presented at different intervals after the diagnostic seizure—for men and women, young and old, and epilepsy of known and unknown cause. With this analysis, the authors have expressed earlier knowledge in a new form, which serves to refine our understanding of an important prognostic aspect of epilepsy. The critical question is what the reasons might be for the reduced life expectancy in people with new-onset epilepsy. Gaitatzis’ data, as indeed other population-based studies, strongly suggest that the increased mortality is related to the underlying cause of epilepsy rather than to the seizures.2,4–8 One may therefore ask, for example, how different life expectancy would be for a person with poststroke epilepsy compared with someone who has had a stroke but not developed epilepsy. Indeed, such patients might constitute the most relevant control group to clarify the contribution of the epilepsy itself. In fact, the reported causes of death in the NGPSE cohort, mainly cancer, ischaemic heart disease, cerebrovascular disease, and pneumonia,2 also indicate that mortality as a consequence of seizures is rare in newly diagnosed patients. Although the estimates of life expectancy are of considerable interest for researchers and physicians, they are probably less useful in counselling patients and relatives. First, it is difficult to generalise from these data because Gaitatzis and colleagues included patients with single seizures and acute symptomatic seizures, while excluding those with brain tumours. Second, epilepsy is a heterogeneous disorder with
558
multiple causes, each affecting the prognosis differently. Because of the limited size of the cohort, patients with different causes were lumped into one group: symptomatic epilepsy. However, it does not make much sense to estimate life expectancy for an individual with epilepsy after a traumatic brain injury on the basis of data from patients with underlying cerebrovascular disease. Third, the concept of years of lost life might be difficult to communicate to patients. A person with idiopathic/cryptogenic epilepsy would probably consider an estimated reduction in life expectancy of up to 2 years highly significant rather than minimal. Although this extended analysis of the NGPSE data provides a new and interesting perspective on mortality risks, we now need to find ways to estimate the contribution of the epilepsy and seizures themselves10 and the causes of such deaths, and to analyse to what extent treatment can minimise risks and reduce years of lost life for people with epilepsy. Finally, we should acknowledge that the available data on mortality in epilepsy derive almost exclusively from western industrialised countries. We lack information from the rest of the world where the vast majority of the global epilepsy population resides and where epilepsy-related mortality and life expectancy is likely to be different.
*Torbjörn Tomson, Lars Forsgren Department of Clinical Neuroscience, Section of Neurology, Karolinska Institutet, SE- 171 76 Stockholm, Sweden (TT): and Department of Pharmacology and Clinical Neuroscience, Section of Neurology, Umeå University, Umeå, Sweden (LF) [email protected] We declare that we have no conflict of interest. 1
2
3 4 5
6
7 8
9 10
Gaitatzis A, Johnson AL, Chadwick DW, Shorvon SD, Sander JW. Life expectancy in people with newly diagnosed epilepsy. Brain 2004; 127: 2427–32. Lhatoo SD, Johnson AL, Goodridge DM, MacDonald BK, Sander JWAS, Shorvon SD. Mortality in epilepsy in the first 11–14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort. Ann Neurol 2001; 49: 336–44. Zielinski JJ. Epilepsy and mortality rate and cause of death. Epilepsia 1974; 15: 191–201. Hauser WA, Annegers J, Elveback L. Mortality in patients with epilepsy. Epilepsia 1980; 21: 399–412. Cockerell O, Johnson A, Sander JWAS, Hart Y, Goodridge D, Shorvon S. Mortality from epilepsy: results from a prospective population based study. Lancet 1994; 344: 918–21. Olafsson E, Hauser WA, Gudmundsson G. Long-term survival of people with unprovoked seizures: a population-based study. Epilepsia 1998; 39: 89–92. Loiseau J, Picot M-C, Loiseau P. Short-term mortality after a first epileptic seizure: a population-based study. Epilepsia 1999; 40: 1388–93. Lindsten H, Nyström L, Forsgren L. Mortality in an adult cohort with newly diagnosed unprovoked epileptic seizure: a population-based study. Epilepsia 2000; 41: 1469–73. Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975; 16: 1–66. Forsgren L, Edvinsson S-O, Nyström L, Blomquist K. Influence of epilepsy on mortality in mental retardation: an epidemiologic study. Epilepsia 1996; 37: 956–63.
www.thelancet.com Vol 365 February 12, 2005
could lead to use of treatments that lower albumin in the urine and improve renal and cardiac prognosis and reduce the risk of developing diabetic renal disease. Such a screening campaign and primary preventive intervention is feasible.11,12 A consensus of the Amsterdam meeting was presented to the Chief Medical Officer of Europe, Herre Kingma, who promised to take this further to his European colleagues. In the Netherlands, Kingma is considering the possibility to complement the traditional health-screening centres for infants and young children, currently used for monitoring general health and providing vaccinations, with a similar function for adults aimed at early detection and prevention of chronic diseases, for which measurement of albuminuria could be one of the variables to monitor. The ISN is particularly committed to promote the implementation of preventive strategies for kidney and generalised vascular diseases in developing countries. In the mid-1990s, ISN created the Commission for the Global Advancement of Nephrology (COMGAN), with the aim to provide educational programmes for developing countries through teaching programmes, fellowship and visiting scholar programmes, and travel grants. COMGAN’s activities have grown to include programmes aimed to assess research needs, opportunities, and implementation strategies in developing countries and identify the necessary resources required. ISN is willing to promote and support collaborations with health-care authorities and local as well as international scientific societies to identify needs and design specific screening and intervention strategies.
Giuseppe Remuzzi, *Jan J Weening Mario Negri Institute for Pharmacological Research,
Laboratori Negri Bergamo, Bergamo, Italy (GR); and Academic Medical Centre, University of Amsterdam, Department of Pathology, 1105 AZ Amsterdam, Netherlands (JJW) [email protected] GR is chair of ISN COMGAN’s Research Committee and JJW is President of ISN, and both were involved in the organisation of some of the meetings mentioned above. 1
2
3
4 5 6 7
8
9
10
11
12
Xue JL, Ma JZ, Louis TA, Collins AJ. Forecast of the number of patients with end-stage renal disease in the United States to the year 2010. J Am Soc Nephrol 2001; 12: 2753–58. Wild SH, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030: response to Rathman and Giani. Diabetes Care 2004; 27: 2569–70. Moeller S, Gioberge S, Brown G. ESRD patients in 2001: global overview of patients, treatment modalities and development trends. Nephrol Dial Transplant 2002; 17: 2071–76. Lysaght MJ. Maintenance dialysis population dynamics: current trends and long-term implications. J Am Soc Nephrol 2002; 13 (suppl 1): S37–40. Barsoum RS. Overview: end-stage renal disease in the developing world. Artif Organs 2002; 26: 737–46. Brenner BM. Retarding the progression of renal disease. Kidney Int 2003; 64: 370–78. Brenner BM, Zagrobelny J. Clinical renoprotection trials involving angiotensin II-receptor antagonists and angiotensin-converting-enzyme inhibitors. Kidney Int Suppl 2003; Feb: S77–85. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. Lancet 1997; 349: 1857–63. Brenner BM, Cooper ME, de Zeeuw D, for the RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–69. Hillege HL, Fidler V, Diercks GF, for the Prevention of Renal and Vascular End Stage Disease (PREVEND) Study Group. Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population. Circulation 2002; 106: 1777–82. Ruggenenti P, Fassi A, Ilieva AP, for the Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) Investigators. Preventing microalbuminuria in type 2 diabetes. N Engl J Med 2004; 351: 1941–51. Verhave JC, Gansevoort RT, Hillege HL, for the PREVEND Study Group. An elevated urinary albumin excretion predicts de novo development of renal function impairment in the general population. Kidney Int Suppl 2004; Nov: S18–21.
Life expectancy in epilepsy Does a diagnosis of epilepsy reduce a person’s life expectancy? According to Athanasios Gaitatzis and colleagues the answer is yes, but under certain circumstances and to a variable extent.1 These authors recently estimated life expectancy in people with epilepsy, with data from the prospective community-based UK National General Practice Study of Epilepsy (NGPSE),2 and made comparisons with the general population. Life expectancy can be reduced by up to 10 years when there is a known cause of the epilepsy, the estimated reduction being highest at the time of diagnosis. These observations are hardly surprising considering the wealth of literature that shows increased mortality rates in people with epilepsy. Traditionally, mortality has been expressed as the ratio of the observed and expected numbers of death: the standardised mortality ratio. Expected deaths are calculated by www.thelancet.com Vol 365 February 12, 2005
applying the death rates of an external reference population to the age distribution of the study population. The epilepsy population has an standardised mortality ratio of 2–3 (ie, a mortality that is 2–3 times higher than that of the general population).3–8 People with epilepsy of unknown cause have at most only a slight increase in mortality, while those with epilepsy as a symptom of a known underlying cause largely account for the overall increased mortality. The increase is evident during the first years after the onset of epilepsy, and mortality then declines to levels close to those in the general population. However, some studies show an increase in mortality later, a decade or more after disease onset.4,8 Relative survivorship, defined as the proportion of observed to expected number of survivors, provides a different perspective of mortality. The relative survivorship at 5, 10, and 15 years after diagnosis was 91%, 557
Comment
Science Photo Library
Rights were not granted to include this image in electronic media. Please refer to the printed journal.
85% and 83%, respectively, in a pioneering study.9 In epilepsy of unknown cause relative survivorship is as high as 96% 25 years after diagnosis.6 Gaitatzis and colleagues introduce yet another way of analysing data on mortality in patients with epilepsy. The estimated life expectancy of people with new-onset nonfebrile seizures from the UK followed up for a median of 15 years was compared with that in people of the same age and sex in the general population. The difference in life expectancy between these populations gives the estimated years of life lost, which is presented at different intervals after the diagnostic seizure—for men and women, young and old, and epilepsy of known and unknown cause. With this analysis, the authors have expressed earlier knowledge in a new form, which serves to refine our understanding of an important prognostic aspect of epilepsy. The critical question is what the reasons might be for the reduced life expectancy in people with new-onset epilepsy. Gaitatzis’ data, as indeed other population-based studies, strongly suggest that the increased mortality is related to the underlying cause of epilepsy rather than to the seizures.2,4–8 One may therefore ask, for example, how different life expectancy would be for a person with poststroke epilepsy compared with someone who has had a stroke but not developed epilepsy. Indeed, such patients might constitute the most relevant control group to clarify the contribution of the epilepsy itself. In fact, the reported causes of death in the NGPSE cohort, mainly cancer, ischaemic heart disease, cerebrovascular disease, and pneumonia,2 also indicate that mortality as a consequence of seizures is rare in newly diagnosed patients. Although the estimates of life expectancy are of considerable interest for researchers and physicians, they are probably less useful in counselling patients and relatives. First, it is difficult to generalise from these data because Gaitatzis and colleagues included patients with single seizures and acute symptomatic seizures, while excluding those with brain tumours. Second, epilepsy is a heterogeneous disorder with
558
multiple causes, each affecting the prognosis differently. Because of the limited size of the cohort, patients with different causes were lumped into one group: symptomatic epilepsy. However, it does not make much sense to estimate life expectancy for an individual with epilepsy after a traumatic brain injury on the basis of data from patients with underlying cerebrovascular disease. Third, the concept of years of lost life might be difficult to communicate to patients. A person with idiopathic/cryptogenic epilepsy would probably consider an estimated reduction in life expectancy of up to 2 years highly significant rather than minimal. Although this extended analysis of the NGPSE data provides a new and interesting perspective on mortality risks, we now need to find ways to estimate the contribution of the epilepsy and seizures themselves10 and the causes of such deaths, and to analyse to what extent treatment can minimise risks and reduce years of lost life for people with epilepsy. Finally, we should acknowledge that the available data on mortality in epilepsy derive almost exclusively from western industrialised countries. We lack information from the rest of the world where the vast majority of the global epilepsy population resides and where epilepsy-related mortality and life expectancy is likely to be different.
*Torbjörn Tomson, Lars Forsgren Department of Clinical Neuroscience, Section of Neurology, Karolinska Institutet, SE- 171 76 Stockholm, Sweden (TT): and Department of Pharmacology and Clinical Neuroscience, Section of Neurology, Umeå University, Umeå, Sweden (LF) [email protected] We declare that we have no conflict of interest. 1
2
3 4 5
6
7 8
9 10
Gaitatzis A, Johnson AL, Chadwick DW, Shorvon SD, Sander JW. Life expectancy in people with newly diagnosed epilepsy. Brain 2004; 127: 2427–32. Lhatoo SD, Johnson AL, Goodridge DM, MacDonald BK, Sander JWAS, Shorvon SD. Mortality in epilepsy in the first 11–14 years after diagnosis: multivariate analysis of a long-term, prospective, population-based cohort. Ann Neurol 2001; 49: 336–44. Zielinski JJ. Epilepsy and mortality rate and cause of death. Epilepsia 1974; 15: 191–201. Hauser WA, Annegers J, Elveback L. Mortality in patients with epilepsy. Epilepsia 1980; 21: 399–412. Cockerell O, Johnson A, Sander JWAS, Hart Y, Goodridge D, Shorvon S. Mortality from epilepsy: results from a prospective population based study. Lancet 1994; 344: 918–21. Olafsson E, Hauser WA, Gudmundsson G. Long-term survival of people with unprovoked seizures: a population-based study. Epilepsia 1998; 39: 89–92. Loiseau J, Picot M-C, Loiseau P. Short-term mortality after a first epileptic seizure: a population-based study. Epilepsia 1999; 40: 1388–93. Lindsten H, Nyström L, Forsgren L. Mortality in an adult cohort with newly diagnosed unprovoked epileptic seizure: a population-based study. Epilepsia 2000; 41: 1469–73. Hauser WA, Kurland LT. The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia 1975; 16: 1–66. Forsgren L, Edvinsson S-O, Nyström L, Blomquist K. Influence of epilepsy on mortality in mental retardation: an epidemiologic study. Epilepsia 1996; 37: 956–63.
www.thelancet.com Vol 365 February 12, 2005