Abstract
Objective: To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. Methods: We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives). Results: Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives. Conclusions: Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1965-1971 |
| Number of pages | 7 |
| Journal | Neurology |
| Volume | 77 |
| Issue number | 22 |
| DOIs | |
| State | Published - Nov 29 2011 |
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ASJC Scopus subject areas
- Clinical Neurology
- Arts and Humanities (miscellaneous)
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Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype. / Kaufmann, Petra; Engelstad, K.; Wei, Y.; Kulikova, R.; Oskoui, M.; Sproule, D. M.; Battista, V.; Koenigsberger, D. Y.; Pascual, J. M.; Shanske, S.; Sano, M.; Mao, X.; Hirano, M.; Shungu, D. C.; DiMauro, S.; De Vivo, D. C.
In: Neurology, Vol. 77, No. 22, 29.11.2011, p. 1965-1971.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Natural history of MELAS associated with mitochondrial DNA m.3243A>G genotype
AU - Kaufmann, Petra
AU - Engelstad, K.
AU - Wei, Y.
AU - Kulikova, R.
AU - Oskoui, M.
AU - Sproule, D. M.
AU - Battista, V.
AU - Koenigsberger, D. Y.
AU - Pascual, J. M.
AU - Shanske, S.
AU - Sano, M.
AU - Mao, X.
AU - Hirano, M.
AU - Shungu, D. C.
AU - DiMauro, S.
AU - De Vivo, D. C.
PY - 2011/11/29
Y1 - 2011/11/29
N2 - Objective: To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. Methods: We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives). Results: Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives. Conclusions: Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.
AB - Objective: To describe the natural history of clinical and laboratory features associated with the m.3243A>G mitochondrial DNA point mutation. Natural history data are needed to obtain prognostic information and for clinical trial planning. Methods: We included 85 matrilineal relatives from 35 families with at least 2 visits in this prospective cohort study. Thirty-one were fully symptomatic with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and 54 were carrier relatives. Evaluations included standardized questionnaires (medical history and daily living functioning), physical examination, neuropsychological testing, and a battery of imaging and laboratory tests. We evaluated changes in clinical and laboratory features over time and survival. Outcomes are reported over a follow-up period of up to 10.6 years (mean 3.8 ± 2.2 years for patients and 5.5 ± 3.0 for carrier relatives). Results: Neurologic examination, neuropsychological testing, and daily living scores significantly declined in all patients with MELAS, whereas no significant deterioration occurred in carrier relatives. Cerebral MRI scores declined significantly in patients with MELAS. Magnetic resonance spectroscopy estimates of lactate in the lateral ventricles increased over time, and high lactate was associated with increased mortality. Symptom onset in childhood often was associated with worse outcome. Patients with MELAS had a greater death rate than carrier relatives. Conclusions: Patients with MELAS carrying the m.3243A>G mutation show a measurable decline in clinical and imaging outcomes. It is hoped that these data will be helpful in anticipating the disease course and in planning clinical trials for MELAS.
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U2 - 10.1212/WNL.0b013e31823a0c7f
DO - 10.1212/WNL.0b013e31823a0c7f
M3 - Article
C2 - 22094475
AN - SCOPUS:82955225292
VL - 77
SP - 1965
EP - 1971
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 22
ER -