TY - JOUR
T1 - Natural history of spinal and bulbar muscular atrophy (SBMA)
T2 - A study of 223 Japanese patients
AU - Atsuta, Naoki
AU - Watanabe, Hirohisa
AU - Ito, Mizuki
AU - Banno, Haruhiko
AU - Suzuki, Keisuke
AU - Katsuno, Masahisa
AU - Tanaka, Fumiaki
AU - Tamakoshi, Akiko
AU - Sobue, Gen
N1 - Funding Information:
This study was supported by a COE grant from the Ministry of Education, Science and Sports of Japan and grants from the Ministry of Welfare, Health and Labor of Japan.
PY - 2006/6
Y1 - 2006/6
N2 - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motoneuron disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene and for which no curative therapy exists. However, since recent research may provide opportunities for medical treatment, information concerning the natural history of SBMA would be beneficial in planning future clinical trials. We investigated the natural course of SBMA as assessed by nine activities of daily living (ADL) milestones in 223 Japanese SBMA patients (mean age at data collection = 55.2 years; range = 30-87 years) followed from 1 to 20 years. All the patients were diagnosed by genetic analysis. Hand tremor was an early event that was noticed at a median age of 33 years. Muscular weakness occurred predominantly in the lower limbs, and was noticed at a median age of 44 years, followed by the requirement of a handrail to ascend stairs at 49, dysarthria at 50, dysphagia at 54, use of a cane at 59 and a wheelchair at 61 years. Twenty-one of the patients developed pneumonia at a median age of 62 and 15 of them died at a median age of 65 years. The most common cause of death in these cases was pneumonia and respiratory failure. The ages at onset of each ADL milestone were strongly correlated with the length of CAG repeats in the AR gene. However CAG-repeat length did not correlate with the time intervals between each ADL milestone, suggesting that although the onset age of each ADL milestone depends on the CAG-repeat length in the AR gene, the rate of disease progression does not. The levels of serum testosterone, an important triggering factor for polyglutamine-mediated motoneuron degeneration, were maintained at relatively high levels even at advanced ages. These results provide beneficial information for future clinical therapeutic trials, although further detailed prospective studies are also needed.
AB - Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motoneuron disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene and for which no curative therapy exists. However, since recent research may provide opportunities for medical treatment, information concerning the natural history of SBMA would be beneficial in planning future clinical trials. We investigated the natural course of SBMA as assessed by nine activities of daily living (ADL) milestones in 223 Japanese SBMA patients (mean age at data collection = 55.2 years; range = 30-87 years) followed from 1 to 20 years. All the patients were diagnosed by genetic analysis. Hand tremor was an early event that was noticed at a median age of 33 years. Muscular weakness occurred predominantly in the lower limbs, and was noticed at a median age of 44 years, followed by the requirement of a handrail to ascend stairs at 49, dysarthria at 50, dysphagia at 54, use of a cane at 59 and a wheelchair at 61 years. Twenty-one of the patients developed pneumonia at a median age of 62 and 15 of them died at a median age of 65 years. The most common cause of death in these cases was pneumonia and respiratory failure. The ages at onset of each ADL milestone were strongly correlated with the length of CAG repeats in the AR gene. However CAG-repeat length did not correlate with the time intervals between each ADL milestone, suggesting that although the onset age of each ADL milestone depends on the CAG-repeat length in the AR gene, the rate of disease progression does not. The levels of serum testosterone, an important triggering factor for polyglutamine-mediated motoneuron degeneration, were maintained at relatively high levels even at advanced ages. These results provide beneficial information for future clinical therapeutic trials, although further detailed prospective studies are also needed.
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U2 - 10.1093/brain/awl096
DO - 10.1093/brain/awl096
M3 - Article
C2 - 16621916
AN - SCOPUS:33745115069
SN - 0006-8950
VL - 129
SP - 1446
EP - 1455
JO - Brain
JF - Brain
IS - 6
ER -