Preview

Epilepsy and paroxysmal conditions

Advanced search

Features of brain electrical activity in adult patients with POLG-related disorders

https://doi.org/10.17749/2077-8333/epi.par.con.2020.041

Full Text:

Abstract

Introduction. Epilepsy is a common feature of mitochondrial disorders, including those associated with mutations in the POLG gene. Nevertheless, brain electrical activity features of POLG-related disorders in adult patients have not been adequately studied.
Objective. To study the features and characteristics of the electroencephalography (EEG) pattern in adult patients with POLG-related disorders.
Material and methods. Eight patients were examined: 7 with SANDO (Sensory Ataxic Neuropathy, Dysarthria, Ophthalmoparesis) syndrome, and 1 with MEMSA (Myoclonic Epilepsy Myopathy Sensory Ataxia) syndrome; median age was 32.5 years. All patients underwent routine EEG monitoring using a 19-channel electroencephalograph according to the generally accepted method.
Results. Epileptic seizures were found in 3 patients, for 2 of them – as the first manifestation of the disease. In 6 patients, theta waves predominated in the occipital regions. Of those 6 patients, in 5 bilateral synchronous bursts of theta and delta wave groups were identified being more prominent in the frontocentral regions; 4 patients had transient non-lateralized delta activity in the occipital and parieto-occipital brain regions. In all patients, opening eyes led to the depression of rhythms and burst suppression. After photostimulation, in 2 cases bilateral synchronous bursts of delta and theta wave groups were recorded predominantly in frontal lobes. In 3 patients during hyperventilation an increase in delta activity in the occipital lobes and bilateral synchronous bursts of delta wave groups were observed. Epileptiform activity was recorded in 2 cases.
Conclusion. In adult patients with POLG-related disorders, regardless of the clinical manifestation, typical EEG features include generalized background slowing, theta and delta bursts in occipital lobes with their suppression by opening eyes.

About the Authors

P. A. Fedin
Research Center of Neurology
Russian Federation

Pavel A. Fedin – Cand. Med. Sc., Leading Researcher, Laboratory of Clinical Neurophysiology

RSCI SPIN-code: 4717-2751

80 Volokolamskoye shosse, Moscow 125367



E. P. Nuzhnyi
Research Center of Neurology
Russian Federation

Evgenii P. Nuzhnyi – Cand. Med. Sc., Neurologist, 5th Neurological Department

RSCI SPIN-code: 5571-3386

80 Volokolamskoye shosse, Moscow 125367



T. Yu. Noskova
Research Center of Neurology
Russian Federation

Tatiana Yu. Noskova – Cand. Med. Sc., Senior Researcher, Scientific and Consulting Department

RSCI SPIN-code: 2742-2148

80 Volokolamskoye shosse, Moscow 125367



Yu. A. Seliverstov
Research Center of Neurology
Russian Federation

Yury A. Seliverstov – Cand. Med. Sc., Researcher, Department of Scientific Coordination and Education

RSCI SPIN-code: 3876-6987

80 Volokolamskoye shosse, Moscow 125367



S. A. Klyushnikov
Research Center of Neurology
Russian Federation

Sergey A. Klyushnikov – Cand. Med. Sc., Leading Researcher, 5th Neurological Department

RSCI SPIN-code: 1769-2262

80 Volokolamskoye shosse, Moscow 125367



T. D. Krylova
Bochkov Research Centre for Medical Genetics
Russian Federation

Tatiana D. Krylova – Researcher, Laboratory of Hereditary Metabolic Diseases

RSCI SPIN-code: 8335-2050

1 Moskvorechye Str., Moscow 115522



P. G. Tsygankova
Bochkov Research Centre for Medical Genetics
Russian Federation

Polina G. Tsygankova – Cand. Biol. Sc., Senior Researcher, Laboratory of Hereditary Metabolic Diseases

RSCI SPIN-code: 1121-3671

1 Moskvorechye Str., Moscow 115522



E. Yu. Zakharova
Bochkov Research Centre for Medical Genetics
Russian Federation

Ekaterina Yu. Zakharova – Dr. Med. Sc., Head of Laboratory of Hereditary Metabolic Diseases

RSCI SPIN-code: 7296-6097

1 Moskvorechye Str., Moscow 115522



S. N. Illarioshkin
Research Center of Neurology
Russian Federation

Sergey N. Illarioshkin – Dr. Med. Sc., Professor, Corresponding Member of RAS, Head of the Department of Brain Research

RSCI SPIN-code: 8646-9426

80 Volokolamskoye shosse, Moscow 125367



References

1. Rudenskaya G.E., Zakharova E.Yu. Hereditary neurometabolic diseases of youth and adult age. Мoscow: GEOTAR-Media; 2018 (in Russ.).

2. Rahman S., Copeland W.C. POLG-related disorders and their neurological manifestations. Nat Rev Neurol. 2019; 15 (1): 40–52. https://doi.org/10.1038/s41582-018-0101-0.

3. Stumpf J.D., Saneto R.P., Copeland W.C. Clinical and molecular features of POLG-related mitochondrial disease. Cold Spring Harb Perspect Biol. 2013; 5 (4): a011395. https://doi.org/10.1101/cshperspect.a011395.

4. Horvath R., Hudson G., Ferrari G., et al. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain. 2006; 129 (Pt 7): 1674–84. https://doi.org/10.1093/brain/awl088.

5. Engelsen B.A., Tzoulis C., Karlsen B., et al. POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection. Brain. 2008; 131 (Pt 3): 818–28. https://doi.org/10.1093/brain/awn007.

6. Anagnostou M.E., Ng Y.S., Taylor R.W., McFarland R. Epilepsy due to mutations in the mitochondrial polymerase gamma (POLG) gene: a clinical and molecular genetic review. Epilepsia. 2016; 57 (10): 1531–45. https://doi.org/10.1111/epi.13508.

7. Mikhailova S.V., Zakharova E.Yu., Tsygankova P.G., et al. Clinical polymorphism of mitochondrial encephalomyopathies caused by polymerase gamma gene mutations. Russian Bulletin of Perinatology and Pediatrics. 2012; 57 (4-2): 54–61 (in Russ.).

8. Zavadenko N.N., Kholin A.A. Epilepsy in children with mytochondrial diseases: diagnostics and treatment features. Epilepsy and Paroxysmal Conditions. 2012; 4 (2): 21–7 (in Russ.).

9. Batysheva T.T., Trepilets V.M., Akhadova L.Y., Golosnaya G.S. Alpers–Huttenlocher syndrome. Epilepsy and Paroxysmal Conditions. 2015; 7 (1): 46–55 (in Russ.).

10. Abramycheva N.Yu., Fedotova E.Yu., Klyushnikov S.A., et al. An original target genetic panel to diagnose neurodegenerative diseases on the basis of next-generation sequencing: first experience. Modern Technologies in Medicine. 2016; 8 (4): 185–90 (in Russ.). https://doi.org/0.17691/stm2016.8.4.23.

11. Guidelines for carrying out of routine EEG of neurophysiology expert board of Russian League Against Epilepsy. Epilepsy and Paroxysmal Conditions. 2016; 8 (4): 99–108 (in Russ.).

12. Nuzhniy Ye.P., Klyushnikov S.A., Seliverstov Yu.A., et al. Sensory ataxic neuropathy, dysarthria and ophthalmoparesis (SANDO syndrome): characteristics of a series of clinical observations in Russia. Annals of Clinical and Experimental Neurology. 2019; 13 (2): 5–13 (in Russ.). https://doi.org/10.25692/ACEN.2019.2.1.

13. Canafoglia L., Franceschetti S., Antozzi C., et al. Epileptic phenotypes associated with mitochondrial disorders. Neurology. 2001; 56 (10): 1340–6. https://doi.org/10.1212/wnl.56.10.1340.

14. Debray F.G., Lambert M., Chevalier I., et al. Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases. Pediatrics. 2007; 119 (4): 722–33. https://doi.org/10.1542/peds.2006-1866.

15. Khurana D.S., Salganicoff L., Melvin J.J., et al. Epilepsy and respiratory chain defects in children with mitochondrial encephalopathies. Epilepsia. 2008; 39 (11): 8–13. https://doi.org/10.1055/s-2008-1076737.

16. Rahman S. Pathophysiology of mitochondrial disease causing epilepsy and status epilepticus. Epilepsy Behav. 2015; 49: 71–5. https://doi.org/10.1016/j.yebeh.2015.05.003.

17. Whittaker R.G., Devine H.E., Gorman G.S., et al. Epilepsy in adults with mitochondrial disease: a cohort study. Ann Neurol. 2015; 78 (6): 949–57. https://doi.org/10.1002/ana.24525.

18. Winterthun S., Ferrari G., He L., et al. Autosomal recessive mitochondrial ataxic syndrome due to mitochondrial polymerase gamma mutations. Neurology. 2005; 64 (7): 1204–8. https://doi.org/10.1212/01.WNL.0000156516.77696.5A.

19. Hikmat O., Eichele T., Tzoulis C., Bindoff L. Understanding the epilepsy in POLG related disease. Int J Mol Sci. 2017; 18 (9): 1845. https://doi.org/10.3390/ijms18091845.

20. Wolf N.I., Rahman S., Schmitt B., et al. Status epilepticus in children with Alpers' disease caused by POLG1 mutations: EEG and MRI features. Epilepsia. 2009; 50 (6): 1596–1607. https://doi.org/10.1111/j.1528-1167.2008.01877.x.

21. Tzoulis C., Tran G.T., Coxhead J., et al. Molecular pathogenesis of polymerase gamma-related neurodegeneration. Ann Neurol. 2014; 76 (1): 76–81. https://doi.org/10.1002/ana.24185.

22. Twomey J.A., Abbott R.J., Franks A.J., Hakin N.J. Status epilepticus complicating migraine. Acta Neurol Scand. 1988; 77 (4): 335–8. https://doi.org/10.1111/j.1600-0404.1988.tb05919.x.

23. Ekstein D., Schachter S.C. Postictal headache. Epilepsy Behav. 2010; 19 (2): 151–5. https://doi.org/10.1016/j.yebeh.2010.06.023.

24. Roshal D., Glosser D., Zangaladze A. Parieto-occipital lobe epilepsy caused by a POLG1 compound heterozygous A467T/W748S genotype. Epilepsy Behav. 2011; 21 (2): 206–10. https://doi.org/10.1016/j.yebeh.2011.03.003.

25. McFarland R., Hudson G., Taylor R.W., et al. Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1). Arch Dis Child. 2008; 93 (2): 151–3. https://doi.org/10.1136/adc.2007.122911.

26. Bindoff L.A., Engelsen B.A. Mitochondrial diseases and epilepsy. Epilepsia. 2012; 53 (Suppl 4): 92–7. https://doi.org/10.1111/j.1528-1167.2012.03618.x.


For citation:


Fedin P.A., Nuzhnyi E.P., Noskova T.Yu., Seliverstov Yu.A., Klyushnikov S.A., Krylova T.D., Tsygankova P.G., Zakharova E.Yu., Illarioshkin S.N. Features of brain electrical activity in adult patients with POLG-related disorders. Epilepsy and paroxysmal conditions. 2020;12(4):205-215. (In Russ.) https://doi.org/10.17749/2077-8333/epi.par.con.2020.041

Views: 143


ISSN 2077-8333 (Print)
ISSN 2311-4088 (Online)