Clinical study on mitochondrial encephalomyopathy in 11 subjects_Journal of Epilepsy

Authors：

 LIQiufeng ^1,2 ,  CHENYangmei ¹ , ZENGKebin ³ , XIAOFei ³ , HONGSiqi ⁴

1. Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China;
2. Department of Neurology, Raditional Chinese Medical Hospital of Yubei District, Chongqing 401120, China;
3. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400042, China;
4. Department of Neurology, Children's Hospital of Chongqing Medical University, Chongqing 400014, China;

Corresponding author：

CHENYangmei, Email: chenym1997@sina.com

Keywords：

Mitochondrial encephalomyopathy; Epilepsy; Muscle biopsy; Genetic testing

DOI：

10.7507/2096-0247.20160004

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Objective Mitochondrial encephalomyopathy is a series of diseases that drag in central nervous system and generalized muscles. The pathogenesis of the disease is lack of ATP for the dysfunction of mitochondria. The misdiagnosis rate of the disease is high and the purpose of this study is to improve the recognition and diagnosis of mitochondrial encephalomyopathy and thus, clinicians could take rational treatment in time and improve patients' prognosis. Methods The clinical data of 11 patients with mitochondrial encephalomyopathy were analyzed including the physical data, clinical presentations, laboratory data, neuroimaging findings, muscle biopsy, genetic testing, treatment and prognosis. Reviewing literature and summarizing the clinical characteristics of mitochondrial encephalomyopathy. Results Among the 11 patients with mitochondrial encephalomyopathy, the mean age was 17 years old. 1 case had family history. 7 cases were misdiagnosed in the first clinic visit. The onset of the 11 cases, 9 were paroxysmal and 2 were hidden. In the course, 10 cases had an epileptic seizure. Among the 9 cases who took the determination of serum lactate, 8 was in high level.9 cases had MRI examination and all found abnormality, 10 patients had EEG examination, and 9 cases found abnormality, 6 cases had muscle biopsy and all found the ragged red fiber(RRF). 6 cases had molecular genetic testing, and all found mutations in mitochondrial DNA. Among the 10 cases who had epileptic seizure, 3 cases can be controlled with single kind of antiepileptic drug. The other 7 cases had a recurrence of epilepsy with single kind of antiepileptic drugs, but can be cotrolled after drug adjusting or drug combination. Conclusion Mitochondrial encephalomyopathy is often accompanied by seizure, which is usually found in children, and also often accompanied by systemic muscle symptoms. The clinical manifestations of the disease is not typical, but is complex and varied symptoms, so the clinical misdiagnosis rate is high. Mitochondrial encephalomyopathy mainly involves the main intracranial artery distribution area (parietal lobe, temporal lobe, occipital lobe, etc.) in central nervous system, and can involve more than one part. Patients with mitochondrial myopathy brain are usually detected the elevation of serum lactate levels, but if the lactic acid level is normal, it does not rule out the possibility of the disease, the confirmation of the disease is mainly by muscle biopsy or genetic tests. There is no specific treatment for mitochondrial encephalomyopathy till now, and it still give priority to symptomatic treatment. And the prognosis is poorer.

Citation： LIQiufeng, CHENYangmei, ZENGKebin, XIAOFei, HONGSiqi. Clinical study on mitochondrial encephalomyopathy in 11 subjects. Journal of Epilepsy, 2016, 2(1): 18-23. doi: 10.7507/2096-0247.20160004 Copy

1.	Thorburn DR. Mitochondrial disorders: prevalence, mythsand advances. J Inherit Metab Dis, 2004, 27(3): 349-362.
2.	Lee HF, Chi CS, Tsai CR, et al. Epileptic seizures ininfants and children with mitochondrial diseases. Pediatr Neurol, 2011, 45(11): 169-174.
3.	NI Wolf, JAM Smeitink. Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology, 2002, 59(20): 1402-1405.
4.	J Schmiedel, S Jackson, J Schäfer, et al. Mitochondrial cytopathies. J Neurol, 2003, 250 (31): 267-277.
5.	Khurana DS, Salganicoff L, Melvin JJ, et al. Epilepsy andrespiratory chain defects in children with mitochondrial encephalopathies.Neuro Pediatrics, 2008, 39(1): 8-13.
6.	Parikh S, Cohen BH, Gupta A, et al. Metabolic testing in the pediatric epilepsy unit.PediatrNeurol, 2008, 38(2): 191-195.
7.	Oliveira AR, Valente R, Ramos J, et al. Persistenthyperlactacidaemia: about a clinical case. BMJ Case Rep, 2013, 22(5): 009485.
8.	Jackson MJ, Schaefer JA, Johnson MA, et al.Presention and clinicalinvestigation of mitochondrial respiratory chain disease: a study of 51patients. Brain, 1995, 118( 2): 339-357.
9.	高素琴, 焉传祝, 刘淑萍, 等.单纯型线粒体肌病的临床和病理特点.临床神经病学杂志, 2005, 18( 1): 7-9.
10.	Gieraerts C, Demaerel P, van Damme P, et al. Mitochondrialencephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis on imaging studies. J Comput Assist Tomogr, 2013, 37(10): 279-281.
11.	Iizuka T, Sakai F, Ide T, et al. Regional cerebral bloodflow and cerebrovascular reactivity during chronicstage of stroke-like episodes in MELAS-implication of neurovascular cellular mechanism. Brain Dev, 2008, 30(7): 100-105.
12.	Gilchrist JM, Sikirica M, Stipa E, et al. Adult-onset MELAS Evidence for involvement of neurons as well as cerebral vasculature in stroke-like episodes. Stroke, 1996, 27(5): 420-423.
13.	Clark JM, Marks MP, Adalsteinsson E, et al. MELAS:clinical and pathologic correlations with MRI, xenon/CT, and MR spectroscopy. Neurology, 1996, 46(9): 223-227.
14.	Hoon-Chul Kang, Young-Mock Lee, Heung Dong Kim. Mitochondrial disease and epilepsy. Brain & Development, 2013, 35 (23): 757-761.
15.	Lin CM, Thajeb P. Valproic acid aggravates epilepsy due to MELAS in a patient with an A3243G mutation of mitochondrial DNA. Metab Brain Dis, 2007, 22 (16): 105-109.
16.	Lam CW, Lau CH, Williams JC, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy. Eur J Pediatr, 1997, 15(6): 562-564.
17.	Galimberti CA, Diegoli M, Sartori I, et al. Brain pseudoatrophy and mental regression on valproate and a mitochondrial DNA mutation. Neurology, 2006, 67(12): 1715-1717.
18.	Chabrol B, Mancini J, Chretien D, et al. Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency. Eur J Pediatr, 1994, 153(22): 133-135.
19.	Isohanni P, Hakonen AH, Euro L, et al. POLG1 manifestationsin childhood. Neurology, 2011, 76(10): 811-815.
20.	Uusimaa J, Hinttala R, Rantala H, et al. Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. Epilepsia, 2008, 49(23): 1038-1045.
21.	Wolf NI, Rahman S, Schmitt B, et al. Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features. Epilepsia, 2009, 50(13): 1596-1607.
22.	Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila), 2009, 47(11):101-111.
23.	李文娜, 韩涛, 王雪, 等.线粒体脑肌病癫痫的药物治疗进展.中华神经科杂志, 2012, 45(2): 144-146.
24.	田冉, 陈金亮.线粒体肌病10例临床分析.中风与神经疾病杂志, 2014, 13(8): 103-107.
25.	Khurana DS, Valencia I, Goldenthal MJ, et al. Mitochondrial dysfunction in epilepsy. Semin Pediatr Neurol, 2013, 20(3):176-187.

1. Thorburn DR. Mitochondrial disorders: prevalence, mythsand advances. J Inherit Metab Dis, 2004, 27(3): 349-362.
2. Lee HF, Chi CS, Tsai CR, et al. Epileptic seizures ininfants and children with mitochondrial diseases. Pediatr Neurol, 2011, 45(11): 169-174.
3. NI Wolf, JAM Smeitink. Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology, 2002, 59(20): 1402-1405.
4. J Schmiedel, S Jackson, J Schäfer, et al. Mitochondrial cytopathies. J Neurol, 2003, 250 (31): 267-277.
5. Khurana DS, Salganicoff L, Melvin JJ, et al. Epilepsy andrespiratory chain defects in children with mitochondrial encephalopathies.Neuro Pediatrics, 2008, 39(1): 8-13.
6. Parikh S, Cohen BH, Gupta A, et al. Metabolic testing in the pediatric epilepsy unit.PediatrNeurol, 2008, 38(2): 191-195.
7. Oliveira AR, Valente R, Ramos J, et al. Persistenthyperlactacidaemia: about a clinical case. BMJ Case Rep, 2013, 22(5): 009485.
8. Jackson MJ, Schaefer JA, Johnson MA, et al.Presention and clinicalinvestigation of mitochondrial respiratory chain disease: a study of 51patients. Brain, 1995, 118( 2): 339-357.
9. 高素琴, 焉传祝, 刘淑萍, 等.单纯型线粒体肌病的临床和病理特点.临床神经病学杂志, 2005, 18( 1): 7-9.
10. Gieraerts C, Demaerel P, van Damme P, et al. Mitochondrialencephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis on imaging studies. J Comput Assist Tomogr, 2013, 37(10): 279-281.
11. Iizuka T, Sakai F, Ide T, et al. Regional cerebral bloodflow and cerebrovascular reactivity during chronicstage of stroke-like episodes in MELAS-implication of neurovascular cellular mechanism. Brain Dev, 2008, 30(7): 100-105.
12. Gilchrist JM, Sikirica M, Stipa E, et al. Adult-onset MELAS Evidence for involvement of neurons as well as cerebral vasculature in stroke-like episodes. Stroke, 1996, 27(5): 420-423.
13. Clark JM, Marks MP, Adalsteinsson E, et al. MELAS:clinical and pathologic correlations with MRI, xenon/CT, and MR spectroscopy. Neurology, 1996, 46(9): 223-227.
14. Hoon-Chul Kang, Young-Mock Lee, Heung Dong Kim. Mitochondrial disease and epilepsy. Brain & Development, 2013, 35 (23): 757-761.
15. Lin CM, Thajeb P. Valproic acid aggravates epilepsy due to MELAS in a patient with an A3243G mutation of mitochondrial DNA. Metab Brain Dis, 2007, 22 (16): 105-109.
16. Lam CW, Lau CH, Williams JC, et al. Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy. Eur J Pediatr, 1997, 15(6): 562-564.
17. Galimberti CA, Diegoli M, Sartori I, et al. Brain pseudoatrophy and mental regression on valproate and a mitochondrial DNA mutation. Neurology, 2006, 67(12): 1715-1717.
18. Chabrol B, Mancini J, Chretien D, et al. Valproate-induced hepatic failure in a case of cytochrome c oxidase deficiency. Eur J Pediatr, 1994, 153(22): 133-135.
19. Isohanni P, Hakonen AH, Euro L, et al. POLG1 manifestationsin childhood. Neurology, 2011, 76(10): 811-815.
20. Uusimaa J, Hinttala R, Rantala H, et al. Homozygous W748S mutation in the POLG1 gene in patients with juvenile-onset Alpers syndrome and status epilepticus. Epilepsia, 2008, 49(23): 1038-1045.
21. Wolf NI, Rahman S, Schmitt B, et al. Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features. Epilepsia, 2009, 50(13): 1596-1607.
22. Lheureux PE, Hantson P. Carnitine in the treatment of valproic acid-induced toxicity. Clin Toxicol (Phila), 2009, 47(11):101-111.
23. 李文娜, 韩涛, 王雪, 等.线粒体脑肌病癫痫的药物治疗进展.中华神经科杂志, 2012, 45(2): 144-146.
24. 田冉, 陈金亮.线粒体肌病10例临床分析.中风与神经疾病杂志, 2014, 13(8): 103-107.
25. Khurana DS, Valencia I, Goldenthal MJ, et al. Mitochondrial dysfunction in epilepsy. Semin Pediatr Neurol, 2013, 20(3):176-187.

Journal of Epilepsy

Clinical study on mitochondrial encephalomyopathy in 11 subjects

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