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Long-term prognosis of patients with West syndrome in Japan: medical aspects
Brain & Development 23 (2001) 692–694 www.elsevier.com/locate/braindev
Original article
Long-term prognosis of patients with West syndrome in Japan: medical aspects Mikiko Ito a,b,*, Tamaki Kumagai a,c, Yoshihiko Yamazaki a,c, Kayoko Sekijima a,d, Kazue Sakakibara a,e, Yoko Matsutomo a, Fumiko Hijikigawa a, Hisako Yamada a b
a Japanese Epilepsy Association: The Research Committee of Tokyo Chapter, Tokyo, Japan School of Health Sciences Osaka University, 1-7 Yamada-oka, Suita, Osaka565-0871, Japan c Graduate School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan d School of Health Sciences, University of Niigata, Niigata, Japan e Ikeda Public Health Center, Osaka, Japan
Received 22 June 2001; received in revised form 13 July 2001; accepted 29 August 2001
Abstract In this study, West syndrome prognosis over 20 years was described. All information was obtained from the primary caregivers of patients with West syndrome thorough questionnaires. Of the 259 respondents, 117 patients born between 1960 and 1980 were analyzed. At the age of 20 years two patients were deceased, of the surviving patients, 40% of patients had seizures daily or weekly and 25.2% had been seizure-free for at least 3 years. There was significant difference in the seizure persistence value between West syndrome etiologies but not between the birth cohorts; of those born in the 1960s and 1970s. Compared with severe seizure persistence, which was the duration of the existing daily or weekly seizures at each age, there were no significant difference between birth cohorts and West syndrome etiologies. q 2001 Elsevier Science B.V. All rights reserved. Keywords: West syndrome in Japan; Long-term prognosis; Seizure prognosis; Adults with West syndrome history
1. Aims The purpose of this study was to investigate the needs and problems concerning the quality of life of patients with West syndrome (WS) and those of their families. Firstly, with a retrospective cohort study, WS prognoses over the 20 years since the patients were born were described. One of the unique characteristics of this study was the usage of a participatory action research method where the patients’ families were not only the ‘subjects’ but also the ‘objects’, raising research questions and points of discussion. 2. Subjects and methods All information was obtained voluntarily from the primary caregivers of patients with WS through questionnaires by mail. Subjects were recruited through the Japanese Epilepsy Association and referrals from several hospitals. Of the 256 respondents, 117 patients born between 1960 and 1980 were analyzed. The patient data: seizure persistence, * Corresponding author. Fax: 181-6-6879-2553. E-mail address: [email protected] (M. Ito).
the duration of daily seizures and the accomplishments development was compared with influencing factors; the onset of seizure, WS etiologies and their birth cohorts; those born in the 1960s (60s) and 1970s (70s). 2.1. Seizure persistence and the duration of daily seizures Seizure persistence is defined as the sum of years of the existing WS with at least one seizure at each year of age. The duration of daily seizures is defined as the sum of years of the existing daily or weekly seizures at each age, which indicates the degree of intractable epilepsy. To describe the seizure persistence, only 85 of the surviving patients with complete data were used. 2.2. Demographic backgrounds Of the 117 patients, two patients died at the ages of 8 and 16. The mortality rate in this study is lower than in previous studies. The surviving patients ranged from 20 to 40 years of age. The proportion of patients from the birth cohorts of the 60s, the first half of the 70s and the second half of 70s were 27.4, 42.7 and 29.9%, respectively. Seventy-one percent of the respondents were from Tokyo or its municipalities. The
0387-7604/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S03 87- 7604(01)0031 5-1
M. Ito et al. / Brain & Development 23 (2001) 692–694
693
Fig. 1. Histogram of the age of Lennox–Gastaut syndrome diagnosis.
male to female ratio was equal. The proportion of respondents with cryptogenic WS was 12.8%, symptomatic WS was 65.0% and unidentified was 22.2%. At the age of 20 years, 40.0% of patients had seizures daily or weekly, and 25.2% had been seizure free for at least 3 years. 3. Results 1. In previous studies, an early onset of seizures could lead to the prediction of a poor prognosis from an etiological perspective. We investigated the initial medical access patients were given prior to an accurate diagnosis of WS. The age at the onset of seizures, as noted by caregivers, was between 1 and 46 months with a median of 6.5 months in the 60s’ cohort. In both the 70s’ cohorts, the median was 5 months, significantly earlier than that of the 60s’ cohort. Similarly, the time when patients were diagnosed was significantly earlier in both the 70s’ cohorts than in the 60s’ patients. The mean number of medical facilities that patients availed prior to an accurate diagnosis of WS was fewer in younger cohorts. These results show that the accessibility and availability of medicine had improved. 2. The proportion of patients with Lennox–Gastaut syndrome (LGS) was 33.3%. The mean age at diagnosis with LGS was 6.6 years (range: 8 months to 20 years), and 80% were diagnosed by the age of 10. There were no significant differences between the transition rate and birth cohorts, the onset of seizures and WS etiologies (Fig. 1). 3. Treatments used for WS: Of patients with cryptogenic WS, 23.1% received high dose vitamin B6 therapy, as Table 1 Administration rate for WS therapies a
did 6.9% of symptomatic WS patients. The ketogenic diet was given to 15.4% of cryptogenic WS patients and 30.6% of symptomatic WS patients (Table 1). Adrenocorticotropic hormone (ACTH) therapy was given to 66.0% of all WS patients. The administration rate of ACTH therapy appeared to be of no significance with the birth cohorts. The short-term ‘seizure free’ effects of ACTH therapy, in the 60s’ cohort was 15.0%, ‘seizure free’ increased by three times in both 70s’ cohorts. This shows that the ACTH therapy is more effective in the younger cohorts (Table 2). 4. There was no significant difference between the seizure persistence values of the 60s’ cohort (15.4 ^ 7.4) and the two 70s’ cohorts (14.5 ^ 7.3, 12.1 ^ 8.7) (Table 3). Seizure persistence in patients with symptomatic WS was 16:5 ^ 5:7 which was significantly greater than the other WS etiologies (cryptogenic WS, 12:5 ^ 9:0; unidentified, 9:0 ^ 8:8). In the duration of daily seizures, there were no significant differences between WS etiologies. Therefore, WS etiologies had no influence on severe seizure persistence. No significance was found in seizure persistence between the onset of seizures, and age of diagnosis with cerebral palsy. The patients who transited to LGS also appeared to have greater seizure persistence than non-LGS patients. The duration of daily seizures of LGS patients ð14:6 ^ 7:4Þ is 2.4 times as great as in non-LGS patients ð6:2 ^ 8:2Þ. We also analyzed whether the short-term ACTH therapy effects predict a good long-term outcome. The patients with ‘seizure free’ soon after the ACTH therapy was 7:2 ^ 7:3, which was significantly lower than in the other groups including the non-ACTH therapy group. The patients with a ‘seizure decreased’ effect soon after the ACTH therapy were almost as numerous as the Table 2 Short-term effect of ACTH therapy on WS birth cohorts a
Symptomatic WS (%) ðn ¼ 72Þ
Cryptogenic WS Unidentified (%) ðn ¼ 13Þ (%) ðn ¼ 25Þ
98.6 65.3 30.6 6.9 6.9 2.8
100 61.5 15.4 0 23.1 0
1960–1970 Administration rate (%)
Anticonvulsants ACTH Ketogenic diet TRH Vitamin B6 IgG therapy a
Missing data was excluded in this analysis.
100 52 8 4 4 4
1971–1975
71.4 56.8 Mean: 66.0%
Short-term effect of ACTH therapy (%) Free 15.0 48.0 Decreased 45.0 40.0 Remained 40.0 12.0 a
*P , 0:10, n.s., no significance.
1976–1980 74.2
n.s.
47.6 23.8 28.6
*
694
M. Ito et al. / Brain & Development 23 (2001) 692–694
Table 3 Seizure persistence and the duration of daily seizure comparison a By one-way analysis Seizure persistence b
The duration of daily seizure c
Birth cohort 1960–1970 (n ¼ 21) 1971–1975 (n ¼ 44) 1976–1980 (n ¼ 20)
15.4 ^ 7.4 14.5 ^ 7.3 12.1 ^ 8.7
n.s.
9.0 ^ 9.2 10.2 ^ 8.7 8.4 ^ 9.3
n.s.
Cryptogenic (n ¼ 12) Symptomatic (n ¼ 53) Unidentified (n ¼ 20)
12.5 ^ 9.0 16.5 ^ 5.7 9.0 ^ 8.8
***
7.5 ^ 9.4 10.8 ^ 11.8 7.0 ^ 8.5
n.s.
LGS (n ¼ 27) Non-LGS (n ¼ 57)
17.4 ^ 5.6 11.9 ^ 8.2
***
14.6 ^ 7.4 6.2 ^ 8.2
***
7.2 ^ 7.3 16.2 ^ 6.0 17.6 ^ 6.3 15.0 ^ 7.5
***
2.6 ^ 5.0 13.2 ^ 8.2 12.5 ^ 9.5 9.4 ^ 8.8
***
West symdrome etiologies
Lennox–Gastaut syndrome
Short-term effect following ACFH therapy Free (n ¼ 19) Decreased (n ¼ 17) Remained (n ¼ l0) Non-ACTH (n ¼ 28) a b c
Missing data was excluded. ***P , 0.001; n.s., no significance. Seizure persistence is defined as the sum of years of the existing WS with at least one seizure at each year of age. The duration of daily seizures is defined as the sum of years of the existing daily or weekly seizures at each age.
‘frequency remained’ effect patients. We consider that only a good short-term ACTH therapy effect could predict a good long-term outcome. 5. Patients showed poor development with only 53.8% of patients having gained the ability to walk without assistance by age 3. Only 19.1% of patients were able to communicate in a simple manner at age 3, this increasing to 40.9% by age 6. At the time of this investigation, 26.7% of patients were unable to walk without assistance, and 67.9% of patients were unable to utilize public transportation independently. The social lives of adult patients without assistance were limited.
4. Conclusions Over the 40 years since 1960, that the medical establishment has demonstrated its ability, the early diagnosis of WS and ACTH therapy has demonstrated short-term improvements. Seizure persistence and WS etiologies have shown significant difference in their relationship. But no significant differences have been found between the duration of daily seizures and WS etiologies. Only one-fourth of the patients were free from seizures at the age of 20. The data was not compared with medical records, which has limited the results of the study.
Original article
Long-term prognosis of patients with West syndrome in Japan: medical aspects Mikiko Ito a,b,*, Tamaki Kumagai a,c, Yoshihiko Yamazaki a,c, Kayoko Sekijima a,d, Kazue Sakakibara a,e, Yoko Matsutomo a, Fumiko Hijikigawa a, Hisako Yamada a b
a Japanese Epilepsy Association: The Research Committee of Tokyo Chapter, Tokyo, Japan School of Health Sciences Osaka University, 1-7 Yamada-oka, Suita, Osaka565-0871, Japan c Graduate School of Health Sciences and Nursing, University of Tokyo, Tokyo, Japan d School of Health Sciences, University of Niigata, Niigata, Japan e Ikeda Public Health Center, Osaka, Japan
Received 22 June 2001; received in revised form 13 July 2001; accepted 29 August 2001
Abstract In this study, West syndrome prognosis over 20 years was described. All information was obtained from the primary caregivers of patients with West syndrome thorough questionnaires. Of the 259 respondents, 117 patients born between 1960 and 1980 were analyzed. At the age of 20 years two patients were deceased, of the surviving patients, 40% of patients had seizures daily or weekly and 25.2% had been seizure-free for at least 3 years. There was significant difference in the seizure persistence value between West syndrome etiologies but not between the birth cohorts; of those born in the 1960s and 1970s. Compared with severe seizure persistence, which was the duration of the existing daily or weekly seizures at each age, there were no significant difference between birth cohorts and West syndrome etiologies. q 2001 Elsevier Science B.V. All rights reserved. Keywords: West syndrome in Japan; Long-term prognosis; Seizure prognosis; Adults with West syndrome history
1. Aims The purpose of this study was to investigate the needs and problems concerning the quality of life of patients with West syndrome (WS) and those of their families. Firstly, with a retrospective cohort study, WS prognoses over the 20 years since the patients were born were described. One of the unique characteristics of this study was the usage of a participatory action research method where the patients’ families were not only the ‘subjects’ but also the ‘objects’, raising research questions and points of discussion. 2. Subjects and methods All information was obtained voluntarily from the primary caregivers of patients with WS through questionnaires by mail. Subjects were recruited through the Japanese Epilepsy Association and referrals from several hospitals. Of the 256 respondents, 117 patients born between 1960 and 1980 were analyzed. The patient data: seizure persistence, * Corresponding author. Fax: 181-6-6879-2553. E-mail address: [email protected] (M. Ito).
the duration of daily seizures and the accomplishments development was compared with influencing factors; the onset of seizure, WS etiologies and their birth cohorts; those born in the 1960s (60s) and 1970s (70s). 2.1. Seizure persistence and the duration of daily seizures Seizure persistence is defined as the sum of years of the existing WS with at least one seizure at each year of age. The duration of daily seizures is defined as the sum of years of the existing daily or weekly seizures at each age, which indicates the degree of intractable epilepsy. To describe the seizure persistence, only 85 of the surviving patients with complete data were used. 2.2. Demographic backgrounds Of the 117 patients, two patients died at the ages of 8 and 16. The mortality rate in this study is lower than in previous studies. The surviving patients ranged from 20 to 40 years of age. The proportion of patients from the birth cohorts of the 60s, the first half of the 70s and the second half of 70s were 27.4, 42.7 and 29.9%, respectively. Seventy-one percent of the respondents were from Tokyo or its municipalities. The
0387-7604/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S03 87- 7604(01)0031 5-1
M. Ito et al. / Brain & Development 23 (2001) 692–694
693
Fig. 1. Histogram of the age of Lennox–Gastaut syndrome diagnosis.
male to female ratio was equal. The proportion of respondents with cryptogenic WS was 12.8%, symptomatic WS was 65.0% and unidentified was 22.2%. At the age of 20 years, 40.0% of patients had seizures daily or weekly, and 25.2% had been seizure free for at least 3 years. 3. Results 1. In previous studies, an early onset of seizures could lead to the prediction of a poor prognosis from an etiological perspective. We investigated the initial medical access patients were given prior to an accurate diagnosis of WS. The age at the onset of seizures, as noted by caregivers, was between 1 and 46 months with a median of 6.5 months in the 60s’ cohort. In both the 70s’ cohorts, the median was 5 months, significantly earlier than that of the 60s’ cohort. Similarly, the time when patients were diagnosed was significantly earlier in both the 70s’ cohorts than in the 60s’ patients. The mean number of medical facilities that patients availed prior to an accurate diagnosis of WS was fewer in younger cohorts. These results show that the accessibility and availability of medicine had improved. 2. The proportion of patients with Lennox–Gastaut syndrome (LGS) was 33.3%. The mean age at diagnosis with LGS was 6.6 years (range: 8 months to 20 years), and 80% were diagnosed by the age of 10. There were no significant differences between the transition rate and birth cohorts, the onset of seizures and WS etiologies (Fig. 1). 3. Treatments used for WS: Of patients with cryptogenic WS, 23.1% received high dose vitamin B6 therapy, as Table 1 Administration rate for WS therapies a
did 6.9% of symptomatic WS patients. The ketogenic diet was given to 15.4% of cryptogenic WS patients and 30.6% of symptomatic WS patients (Table 1). Adrenocorticotropic hormone (ACTH) therapy was given to 66.0% of all WS patients. The administration rate of ACTH therapy appeared to be of no significance with the birth cohorts. The short-term ‘seizure free’ effects of ACTH therapy, in the 60s’ cohort was 15.0%, ‘seizure free’ increased by three times in both 70s’ cohorts. This shows that the ACTH therapy is more effective in the younger cohorts (Table 2). 4. There was no significant difference between the seizure persistence values of the 60s’ cohort (15.4 ^ 7.4) and the two 70s’ cohorts (14.5 ^ 7.3, 12.1 ^ 8.7) (Table 3). Seizure persistence in patients with symptomatic WS was 16:5 ^ 5:7 which was significantly greater than the other WS etiologies (cryptogenic WS, 12:5 ^ 9:0; unidentified, 9:0 ^ 8:8). In the duration of daily seizures, there were no significant differences between WS etiologies. Therefore, WS etiologies had no influence on severe seizure persistence. No significance was found in seizure persistence between the onset of seizures, and age of diagnosis with cerebral palsy. The patients who transited to LGS also appeared to have greater seizure persistence than non-LGS patients. The duration of daily seizures of LGS patients ð14:6 ^ 7:4Þ is 2.4 times as great as in non-LGS patients ð6:2 ^ 8:2Þ. We also analyzed whether the short-term ACTH therapy effects predict a good long-term outcome. The patients with ‘seizure free’ soon after the ACTH therapy was 7:2 ^ 7:3, which was significantly lower than in the other groups including the non-ACTH therapy group. The patients with a ‘seizure decreased’ effect soon after the ACTH therapy were almost as numerous as the Table 2 Short-term effect of ACTH therapy on WS birth cohorts a
Symptomatic WS (%) ðn ¼ 72Þ
Cryptogenic WS Unidentified (%) ðn ¼ 13Þ (%) ðn ¼ 25Þ
98.6 65.3 30.6 6.9 6.9 2.8
100 61.5 15.4 0 23.1 0
1960–1970 Administration rate (%)
Anticonvulsants ACTH Ketogenic diet TRH Vitamin B6 IgG therapy a
Missing data was excluded in this analysis.
100 52 8 4 4 4
1971–1975
71.4 56.8 Mean: 66.0%
Short-term effect of ACTH therapy (%) Free 15.0 48.0 Decreased 45.0 40.0 Remained 40.0 12.0 a
*P , 0:10, n.s., no significance.
1976–1980 74.2
n.s.
47.6 23.8 28.6
*
694
M. Ito et al. / Brain & Development 23 (2001) 692–694
Table 3 Seizure persistence and the duration of daily seizure comparison a By one-way analysis Seizure persistence b
The duration of daily seizure c
Birth cohort 1960–1970 (n ¼ 21) 1971–1975 (n ¼ 44) 1976–1980 (n ¼ 20)
15.4 ^ 7.4 14.5 ^ 7.3 12.1 ^ 8.7
n.s.
9.0 ^ 9.2 10.2 ^ 8.7 8.4 ^ 9.3
n.s.
Cryptogenic (n ¼ 12) Symptomatic (n ¼ 53) Unidentified (n ¼ 20)
12.5 ^ 9.0 16.5 ^ 5.7 9.0 ^ 8.8
***
7.5 ^ 9.4 10.8 ^ 11.8 7.0 ^ 8.5
n.s.
LGS (n ¼ 27) Non-LGS (n ¼ 57)
17.4 ^ 5.6 11.9 ^ 8.2
***
14.6 ^ 7.4 6.2 ^ 8.2
***
7.2 ^ 7.3 16.2 ^ 6.0 17.6 ^ 6.3 15.0 ^ 7.5
***
2.6 ^ 5.0 13.2 ^ 8.2 12.5 ^ 9.5 9.4 ^ 8.8
***
West symdrome etiologies
Lennox–Gastaut syndrome
Short-term effect following ACFH therapy Free (n ¼ 19) Decreased (n ¼ 17) Remained (n ¼ l0) Non-ACTH (n ¼ 28) a b c
Missing data was excluded. ***P , 0.001; n.s., no significance. Seizure persistence is defined as the sum of years of the existing WS with at least one seizure at each year of age. The duration of daily seizures is defined as the sum of years of the existing daily or weekly seizures at each age.
‘frequency remained’ effect patients. We consider that only a good short-term ACTH therapy effect could predict a good long-term outcome. 5. Patients showed poor development with only 53.8% of patients having gained the ability to walk without assistance by age 3. Only 19.1% of patients were able to communicate in a simple manner at age 3, this increasing to 40.9% by age 6. At the time of this investigation, 26.7% of patients were unable to walk without assistance, and 67.9% of patients were unable to utilize public transportation independently. The social lives of adult patients without assistance were limited.
4. Conclusions Over the 40 years since 1960, that the medical establishment has demonstrated its ability, the early diagnosis of WS and ACTH therapy has demonstrated short-term improvements. Seizure persistence and WS etiologies have shown significant difference in their relationship. But no significant differences have been found between the duration of daily seizures and WS etiologies. Only one-fourth of the patients were free from seizures at the age of 20. The data was not compared with medical records, which has limited the results of the study.