Pattern analysis of lower limb magnetic resonance images in Korean patients with distal myopathy

Hyung Jun Park; Ha Young Shin; Seung Min Kim; Kee Duk Park; Young-Chul Choi

doi:10.14253/acn.2019.21.2.79

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Park, Shin, Kim, Park, and Choi: Pattern analysis of lower limb magnetic resonance images in Korean patients with distal myopathy

Original Article

Ann Clin Neurophysiol 2017;21(2):79-86.

Published online: 5 January 2017

DOI: https://doi.org/10.14253/acn.2019.21.2.79

Pattern analysis of lower limb magnetic resonance images in Korean patients with distal myopathy

Hyung Jun Park^1,²

, Ha Young Shin²

, Seung Min Kim²

, Kee Duk Park³

, Young-Chul Choi²

¹Department of Neurology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea

²Department of Neurology, Yonsei University College of Medicine, Seoul, Korea

³Department of Neurology, Mokdong Hospital, Ewha Womans University School of Medicine, Seoul, Korea

Correspondence to Young-Chul Choi Department of Neurology, Gangnam Sever-ance Hospital, Yonsei University College of Medicine, 211 Eonju-ro, Gangnam-gu, Seoul 06273, Korea Tel: +82-2-2019-3323 Fax: +82-2-3462-5904 E-mail: ycchoi@yuhs.ac

Received 5 June 201810 July 2018 Accepted 18 July 2018

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

초록

Background

Magnetic resonance (MR) images are useful for diagnosing myopathy. The purpose of this study was to determine the usefulness of lower-limb MR images in Korean patients with distal myopathy.

Methods

We reviewed medical records in the myopathy database from January 2002 to Oc-tober 2016. We selected 21 patients from 91 unrelated families with distal myopathy: four with GNE myopathy, 11 with dysferlinopathy, and six with ADSSL1 myopathy.

Results

Ten (48%) of the 21 patients were men. The ages of the participants at symptom on-set and imaging were 19.2 ± 9.5 and 30.4 ± 9.0 years (mean ± standard deviation), respectively. Their grade on the modified Gardner-Medwin and Walton grade was 3.3 ± 1.7. The strength grade of the knee extensors was not correlated with the Mercuri scale for the quadriceps (r = –0.247, p = 0.115). However, the Medical Research Council grades of the knee flexors, ankle dorsiflexors, and ankle plantar flexors were significantly correlated with the Mercuri scale ratings of the knee flexors (r = –0.497, p = 0.001), tibialis anterior (r = –0.727, p < 0.001), and ankle plantar flexors (r = –0.620, p < 0.001), respectively. T1-weighted MR images showed character-istic fatty replacement patterns that were consistent with the causative genes. Unsupervised hierarchical clustering of the Mercuri scale showed that the main factors contributing to the dichotomy were the causative gene and the clinical severity.

Conclusions

This study is the first to reveal the usefulness of lower-limb MR images in the differential diagnosis of distal myopathy in Korea.

Keywords: Distal myopathies, Magnetic resonance imaging, DYSF, GNE, ADSSL1

REFERENCES

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Fig. 1.

Relationship between muscle strength and the degree of fatty replacement observed in lower-limb magnetic resonance (MR) images. (A) The Mercuri scale rating of the quadriceps (rectus femoris, vastus lateralis, vastus medialis, and vastus intermedius) was not significantly correlated with the Medical Research Council (MRC) grade of the knee extensors (r = –0.247, p = 0.115). (B) The Mercuri scale rating of the knee flexors (semitendinosus, semimembranosus, and the short and long heads of biceps femoris) was significantly correlated with the MRC grade of the knee flexors (r = –0.497, p = 0.001). (C) The Mercuri scale rating of the tibialis anterior was significantly correlated with the MRC grade of the ankle dorsiflexors (r = –0.727, p < 0.001). (D) The Mercuri scale rating of the ankle plantar flexors (soleus and medial/lateral gastrocnemius) was significantly correlated with the MRC grade of the ankle plantar flexors (r = –0.620, p < 0.001).

Fig. 2.

Heat map representing muscle degeneration. GNE myopathy was characterized by the early involvement of the tibialis anterior and the short head of the biceps femoris, with relative sparing of the vastus lateralis. Dysferlinopathy showed the early involvement of the posterior compartment of the calf and thigh muscles, with relative sparing of the sartorius, gracilis, and rectus femoris. ADSSL1 myopathy showed fatty replacements of the gastrocnemius that began at the early stages. Each column in the heat map corresponds to one patient. Each row corresponds to one muscle, in de-scending order from cranial to caudal. A gray–blue–midnight-blue gradient in the heat map indicates increasing fatty substitution (legend at the top). The two rows at the left of the heat map denote individual clinical features: the myopathy group and grade on the modified Gardner-Medwin and Walton (GMW) grade, color coded as indicated in the legend on the left.

Fig. 3.

Hierarchically clustered heat map of Mercuri scale ratings from magnetic resonance (MR) images from 21 patients with distal myopathy. Hierar-chical clustering of the Mercuri scale ratings showed that the included patients could be divided into two distinct subpopulations: one with mild fatty replacement and the other with moderate/severe fatty replacement. The main factors contributing to this dichotomy were the causative gene and the clinical severity (as assessed using the modified GMW grade). Each column corresponds to one patient, and they are hierarchically clustered (dendrogram at the top) based solely on MR imaging data (using the Mercuri scale). Each row in the heat map corresponds to one muscle, in de-scending order from cranial to caudal. A gray-blue-midnight-blue gradient in the heat map indicates increasing fatty substitution (legend at the top). The two rows at the left of the heat map denote individual clinical features (not used in the hierarchical clustering algorithm): the myopathy group and grade on the modified GMW grade, color coded as indicated in the legend on the left. GMW, Gardner-Medwin and Walton.

Table 1.

Clinical and genetic data of the patients with distal myopathy

Patient designation and MF number	Sex	Age at on-set (years)	Age at imaging (years)	Disease duration (years)	Gene	Mutation	Modified gardner-med-win and Walton grade	Serum creatine kinase level (IU/l)	Immunohisto-chem-istry for dysferlin
II-1 in MF1077	M	31	32	1	GNE	c.527A>T + c.1765G>C	2	524	Positive
II-1 in MF1000	M	19	23	4	GNE	c.1219C>T + c.1765G>C	3	1,421	ND
II-1 in MF167	F	32	35	3	GNE	c.1219C>T + c.1765G>C	3	181	ND
II-1 in MF691	M	18	39	21	GNE	c.38G>C + c.1714G>C	8	112	ND
II-2 in MF693	M	21	23	2	DYSF	c.663+1G>C + c.1284+2T>C	1	10,260	ND
II-1 in MF919	M	15	17	2	DYSF	c.663+1G>C + c.1464delT	2	18,486	Positive
II-2 in MF1178	F	20	21	1	DYSF	c.706C>T + c.5884+6C>T	2	19,000	ND
II-1 in MF699	M	29	30	1	DYSF	c.1284+2T>C + c.2494C>T	2	4,578	ND
II-2 in MF1152	F	23	23	0	DYSF	-^a	2	7,022	Negative
II-2 in MF970	F	20	37	17	DYSF	c.663+1G>C + c.2997G>T	3	7,957	Negative
II-1 in MF731	F	16	26	10	DYSF	c.2248C>T + c.5090G>C	3	8,142	ND
II-1 in MF974	M	16	31	15	DYSF	c.2494C>T + c.2494C>T	4	8,350	Negative
I-2 in MF733	F	35	40	5	DYSF	c.2494C>T + c.2997G>T	4	6,706	ND
II-1 in MF571	F	29	39	10	DYSF	c.1464delT + c.3113G>A	5	7,158	Negative
II-5 in MF948	F	33	53	20	DYSF	c.2494C>T + c.2997G>T	7	1,462	ND
II-2 in MF1184	F	8	15	7	ADSSL1	c.910G>A + c.1048delA	2	281	Positive
II-2 in MF1191	F	12	24	12	ADSSL1	c.910G>A + c.1048delA	2	348	ND
II-2 in MF1004	M	6	34	28	ADSSL1	c.910G>A + c.1048delA	3	272	ND
II-1 in MF578	M	5	29	24	ADSSL1	c.910G>A + c.1048delA	3	420	Positive
II-2 in MF416	M	8	30	22	ADSSL1	c.910G>A + c.1048delA	3	250	Positive
I-2 in MF795	F	7	37	30	ADSSL1	c.910G>A + c.1048delA	5	108	ND

ND, not done; F, female; a II-2 in MF1152 patient d; M, male; IU, international unit. id not confirmed genetically, and was diagnosed by the absence of dysferlin staining in immunohistochemistry.

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