Neurology India
menu-bar5 Open access journal indexed with Index Medicus
  Users online: 2046  
 Home | Login 
About Editorial board Articlesmenu-bullet NSI Publicationsmenu-bullet Search Instructions Online Submission Subscribe Videos Etcetera Contact
  Navigate Here 
  » Next article
  » Previous article 
  » Table of Contents
 Resource Links
  »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
  »  Article in PDF (138 KB)
  »  Citation Manager
  »  Access Statistics
  »  Reader Comments
  »  Email Alert *
  »  Add to My List *
* Registration required (free)  

  In this Article
 »  Abstract
 »  Case Report
 »  Discussion
 »  Acknowledgment
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    PDF Downloaded274    
    Comments [Add]    
    Cited by others 9    

Recommend this journal


Year : 2007  |  Volume : 55  |  Issue : 4  |  Page : 385-387

Magnetic resonance spectroscopy study in basal ganglia of patients with myoclonic epilepsy with ragged-red fibers

1 Department of Neurology, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan
2 Department of Medical Imaging, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan
3 Vscular and Genomic center, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500, Taiwan

Date of Acceptance13-Jun-2007

Correspondence Address:
Chin-San Liu
Department of Neurology, Changhua Christian Hospital, 135 Nanhsiao Street, Changhua, 500
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.37096

Rights and Permissions

 » Abstract 

Abnormal magnetic resonance spectroscopic (MRS) signals in the basal ganglia may be one of the characteristics in mitochondrial disease. We report MRS study in a family with myoclonic epilepsy with ragged-red fibers (MERRF). Their MRS studies over the basal ganglia revealed decreased N-acetylaspartate/creatine ratio and increased choline/creatine ratio in the four symptomatic members, but normal in the two asymptomatic members. However, negative MRI study was found in all members of this family. Our report suggests that the increased choline/creatine ratio in basal ganglia MRS may be one of the early information to suspect MERRF disease.

Keywords: Magnetic resonance spectroscopy, myoclonic epilepsy with ragged-red fibers

How to cite this article:
Chuang CS, Lo MC, Lee KW, Liu CS. Magnetic resonance spectroscopy study in basal ganglia of patients with myoclonic epilepsy with ragged-red fibers. Neurol India 2007;55:385-7

How to cite this URL:
Chuang CS, Lo MC, Lee KW, Liu CS. Magnetic resonance spectroscopy study in basal ganglia of patients with myoclonic epilepsy with ragged-red fibers. Neurol India [serial online] 2007 [cited 2021 Jun 18];55:385-7. Available from:

The brain magnetic resonance imaging (MRI) findings in patients with myoclonic epilepsy with ragged-red fibers (MERRF) disease were not specific. [1] The most common one was cerebral and cerebellar atrophy. [2] Some reports stated that the cerebral and cerebellar white matter may have low densities on CT and patchy T2 prolongation on MRI. However, in Kendall half the proven cases did not reveal any abnormality on neuroimage. [2] Basal ganglia of abnormal magnetic resonance spectroscopic (MRS) study may provide further information by looking into regional brain metabolic abnormalities and give a clue for early detection of mitochondrial disease. [3] Therefore we give a brief survey of MRS study, focusing on the basal ganglia, in a MERRF family.

 » Case Report Top

The proband (II-2), a 40-year-old man, presented with insidious onset, slowly progressive unsteadiness and mild cognition decline for 10 years; more difficult in walking or arising from chair in the recent few years. The patient did not have diabetes, hypertension, migraine, drinking or drug abuse. Physical examination showed no short stature or lipoma. Neurological examinations revealed mild wasting and weakness of shoulder and pelvic girdles; marked bilateral dysmetria in the finger-nose-finger test; occasional resting and action myoclonus of the extremities during daily activity. Blood tests disclosed elevated plasma lactate (2.75 mEq/L, normal range: 0.63-2.44 mEq/L), normal plasma vitamin B 12 level and normal RBC morphology. The cardiac ultrasound showed diffuse hypokinesis with impaired left ventricular function. Electroencephalogram revealed symmetric slowing and frequent intermittent generalized epileptiform discharges. The MRI examination was performed in a single session using Philips Intera, 1.5T; multislice transverse and coronal images (Single Voxel Specturm; repetition times 1500 msec; echo time 136msec, measurements 128; WS window 60 Hz; WS-EXC start angle 330; slice thickness, 5 mm) were obtained. The MRI demonstrated mild cerebral and moderate cerebellar atrophy. The MRS study, a box measuring 21 mm anteriorposterior x 15 mm left-right x 20 mm craniocaudal, positioned in the right basal ganglia as the volume of interest (VOI) with single-voxel placed in it, showed prominently reduced NAA/Cr ratio and elevated choline/Cr ratio [Figure - 1]. No lactate signal was noted in basal ganglion from each MRS study. Qualitative and semi-quantitative analyses of mtDNA A8344G point mutation were processed by the polymerase chain reaction and restriction fragment length polymorphism analysis by Nae I restriction enzyme [Figure - 2]. Subjects harboring higher proportion of mtDNA A8344G point mutation have higher choline/Cr ratio. Proband's elder sister (II-1), younger brother (II-3) and nephew (III-1) also have increased plasma lactate, similar MRS pictures and clinical features, including ataxic gait, mental retardation, proximal muscle weakness and myoclonic jerks. The demographic data and clinical findings of the family are summarized in [Table - 1].

 » Discussion Top

Nonspecific brain MRI findings have been reported in patients with mitochondrial diseases, including generalized brain atrophy, hyperintense signal abnormalities in white matter, deep gray nuclei and the brainstem. [1],[2] In MELAS disease (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes) there were multiple stroke-like lesions primarily in the parietal and occipital cortex on T2-weighted MRI. [4] In MERRF disease, there were spongiform degeneration of cerebral white matter and calcifications in the cerebellum/basal ganglia, which showed as low densities in brain CT and hyperintense signal changes in MRI study. [1],[2] However, in Fukuhara's clinicopathological study on MERRF patients, there was neither abnormal signal change of brain MRI nor brain atrophy. [5] In our study, the proband had prominent cerebellar atrophy, which was disproportional with the cerebral atrophy; otherwise there was no any abnormal signal in T1, T2-weighted MRI study.

Proton MRS can provide further information than MRI by looking into regional brain metabolic abnormalities and biomedical pathology. [6] Mathews et al. found remarkable decrease of NAA/Cr ratio in MRS studies of patients with Kerns-Sayre syndrome and MELAS disease. Moreover, the NAA/Cr ratio was found to be decreased in MERRF disease. [4] Kaufmann et al. reported significantly increased ventricular lactate in MELAS family but not in MERRF family. [7]

If we can select the initial lesion site for MRS study, it may provide clues for early detection of the disease. Orcesi published that bilateral putaminal necrosis was associated with MERRF, even when the typical clinical picture was lacking. [8] Therefore, we used the MRS measurement of basal ganglia as a VOI in a family of MERRF disease. Our MRS studies showed reduced NAA/Cr ratio, increased choline/Cr ratio and absent lactate signal in the basal ganglia in all symptomatic patients with MERRF disease. However, normal study of basal ganglia MRS was found in the asymptomatic MERRF patients. Increase of intracellular choline component may be one of possible and rational explanations of the increased ratio of choline/Cr for that the level of Cr is relative constant and can be used as a landmark to indicate the significant alteration of other metabolite enlighten in MRS survey. Choline is the constituent of phospholipid. There are many phospholipids, such as phosphocholine, glycerophosphocholine, phosphatidylcholine and sphingomyelin; [9] and they are the building blocks of cell membranes. The inner and outer mitochondrial membranes also contain abundant phospholipids. Uyama et al. proved the abnormal phospholipid metabolism of mitochondrial membranes in MERRF disease. [10] Therefore the increased choline/Cr ratio may be served as a marker of membrane turnover, either in cell division or in breakdown. [11] Thus, the increased broken products of phospholipids in the brain-targeted region of MERRF patients will be reflected in the MRS study as increased choline/Cr ratio. The elevated choline/Cr ratio was not found in patients with MERRF disease in Mathews's study since the group selected the supraventricular or occipital region as the VOI. [4] However, some secondary damage of basal ganglia including brain tumor, demyelination, chronic hypoxia or HIV may show similar MRS findings, but it can be easily and carefully differentiated from other image study, CSF analysis, serum marker survey and past history. Thus, we prefer using basal ganglia as the VOI of MRS as it is the initial lesion site, especially under the normal study of MRI or CT. Finally, we suggest that increased choline/Cr ratio in basal ganglia MRS may provide useful information for MERRF diagnosis.

 » Acknowledgment Top

We acknowledge the assistance of Dr Shy-Lin Wu, the chief of the department of neurology, Changhua Christian Hospital and Miss Chin-Ling Kuo in the data analysis and figure construction.

 » References Top

1.Barkovich AJ, Good WV, Koch TK, Berg BO. Mitochondrial disorders: Analysis of their clinical and imaging characteristics. AJNR Am J Neuroradiol 1993;14:1119-37.  Back to cited text no. 1  [PUBMED]  
2.Kendall BE. Disorder of lysosomes, peroxysomes and mitochondria. AJNR Am J Neuroradiol 1992;13:621-53.  Back to cited text no. 2  [PUBMED]  
3.Vedolin L, Moura de Souza CF, Schwark R, Lopes B, Laybauer LS, Saraiva Pereira ML, et al . Conventional MRI and MR spectroscopy in nonclassical mitochondrial disease: Report of three patients with mitochondrial DNA deletion. Childs Nerv Syst 2006;22:1355-9.  Back to cited text no. 3    
4.Mathews PM, Andermann F, Silver K, Karpati G, Arnold DL. Proton MR spectroscopic characterization of differences in regional brain metabolic abnormalities in mitochondrial encephalomyopathies. Neurology 1993;43:2484-90.  Back to cited text no. 4  [PUBMED]  
5.Fukuhara N. MERRF: A clinicopathological study: Relationships between myoclonic epilepsies and mitochondrial myopathies. Rev Neurol 1991;147:476-9.  Back to cited text no. 5  [PUBMED]  
6.Parry A, Matthews PM. Roles for imaging in understanding the pathophysiology, clinical evaluation and management of patients with mitochondrial disease. J Neuroimaging 2003;13:293-302.  Back to cited text no. 6  [PUBMED]  
7.Kaufmann P, Shungu DC, Sano MC, Jhung S, Engelstad K, Mitsis E, et al . Cerebral lactic acidosis correlates with neurological impairment in MELAS. Neurology 2004;62:1297-302.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Orcesi S, Gorni K, Termine C, Uggetti C, Veggiotti P, Carrara F, et al . Bilateral putaminal necrosis associated with the mitochondrial DNA A8344G myoclonus epilepsy with ragged red fibers (MERRF) mutation: An infantile case. J Child Neurol 2006;21:79-82.  Back to cited text no. 8  [PUBMED]  
9.Kato T, Hamakawa H, Shioiri T, Murashita J, Takahashi Y, Takahashi S, et al . Choline-containing compounds detected by proton magnetic resonance spectroscopy in the basal ganglia in bipolar disorder. J Psychiatry Neurosci 1996;21:248-54.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Uyama E, Kutsukake Y, Hara A, Uemura K, Uchino M, Mita S, et al . Abnormal excretion of urinary phospholipids and sulfatide in patients with mitochondrial encephalomyopathies. Biochem Biophys Res Commun 1993;194:266-73.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Castillo M, Kwock L, Mukherji SK. Clinical applications of proton MR spectroscopy. AJNR Am J Neuroradiol 1996;17:1-15.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]


  [Figure - 1], [Figure - 2]

  [Table - 1]

This article has been cited by
1 “Myo-cardiomyopathy” is commonly associated with the A8344G “MERRF” mutation
Michela Catteruccia,Donato Sauchelli,Giacomo Della Marca,Guido Primiano,Cristina Cuccagna,Daniela Bernardo,Milena Leo,Antonella Camporeale,Tommaso Sanna,Alessandro Cianfoni,Serenella Servidei
Journal of Neurology. 2015; 262(3): 701
[Pubmed] | [DOI]
2 Myoclonic epilepsy with ragged-red fibers: A case report
Xue-Fan Yu,Jing Miao,Yan Li,Xin-Mei Jiang,Yu-Gang Ma,Hong-Mei Meng
Experimental and Therapeutic Medicine. 2014;
[Pubmed] | [DOI]
3 Congenital-Genetic Inborn Errors of Metabolism Presenting as an Adult or Persisting into Adulthood: Neuroimaging in the More Common or Recognizable Disorders
Shri H. Krishna,Alexander M. McKInney,Leandro T. Lucato
Seminars in Ultrasound, CT and MRI. 2013;
[Pubmed] | [DOI]
4 Mitochondrial dysfunctions in Myalgic Encephalomyelitis / chronic fatigue syndrome explained by activated immuno-inflammatory, oxidative and nitrosative stress pathways
Gerwyn Morris,Michael Maes
Metabolic Brain Disease. 2013;
[Pubmed] | [DOI]
5 Metabolite measurements in the caudate nucleus, anterior cingulate cortex and hippocampus among patients with mitochondrial disorders: a case-control study using proton magnetic resonance spectroscopy
R. E. Anglin,P. I. Rosebush,M. D. Noseworthy,M. Tarnopolsky,A. M. Weber,N. Soreni,M. F. Mazurek
CMAJ Open. 2013; 1(1): E48
[Pubmed] | [DOI]
6 Movement disorders and mitochondrial disease
Moustris, A., Edwards, M.J., Bhatia, K.P.
Handbook of Clinical Neurology. 2011; 100(173): 192
7 Altered mitochondria and Bcl-2 expression in the hippocampal CA3 region in a rat model of acute epilepsy
Cheng, J., Wu, L., Wang, Q., Gan, Y., Liu, G., Yu, H.
Neural Regeneration Research. 2009; 4(4): 276-280
8 Molecular diagnostics and mitochondrial dysfunction: a future perspective
Siciliano, G. and Pasquali, L. and Mancuso, M. and Murri, L.
Expert Review of Molecular Diagnostics. 2008; 8(4): 531-549
9 Molecular diagnostics and mitochondrial dysfunction: a future perspective
Gabriele Siciliano,Livia Pasquali,Michelangelo Mancuso,Luigi Murri
Expert Review of Molecular Diagnostics. 2008; 8(4): 531
[Pubmed] | [DOI]


Print this article  Email this article
Previous article Next article
Online since 20th March '04
Published by Wolters Kluwer - Medknow