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J Clin Neurol
J Clin Neurol
JCN
Journal of Clinical Neurology (Seoul, Korea)
1738-6586
2005-5013
Korean Neurological Association

39227338
10.3988/jcn.2024.0086
Letter to the Editor
Myotonic Dystrophy Type 1 With Cerebellar Ataxia and Cerebellar Atrophy
https://orcid.org/0000-0001-5123-936X
Ling Chen ab
https://orcid.org/0009-0006-4266-0818
Wang Jianchun ab
https://orcid.org/0000-0001-7993-3054
Zheng Yiming ab
https://orcid.org/0000-0001-6069-695X
Sun Yunchuang ab
a Department of Neurology, Peking University First Hospital, Beijing, China.
b Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China.
Correspondence: Yunchuang Sun, MD. Department of Neurology, Peking University First Hospital, No.8, Xishiku Street, Xicheng District, Beijing 100034, China. Tel +86-10-83572588, sychuang0805@163.com
9 2024
22 8 2024
20 5 539541
19 2 2024
03 6 2024
04 7 2024
Copyright © 2024 Korean Neurological Association
2024
Korean Neurological Association
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://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.
National Natural Science Foundation of China >https://doi.org/10.13039/501100001809 82101355 82201550
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pmcDear Editor,

Myotonic dystrophy (DM) is a dominantly inherited muscular dystrophy involving multiple systems.1 We report a case with cerebellar ataxia and cerebellar atrophy that was finally diagnosed as DM type 1 (DM1).

A 50-year-old female presented with a 4-year history of progressive gait imbalance and slurred speech. She had been diagnosed with diabetes about 20 years previously, and had cataracts for 8 years. She developed grip myotonia at the age of 20 years. Her younger brother had diabetes for about 10 years and had been walking unsteadily for almost 2 years. Our patient presented with bilateral temporal muscle atrophy, frontal alopecia, and severe gait ataxia requiring support. A neurological examination revealed dysarthria and weakness of bilateral eyelids and neck flexion. Nystagmus was absent. Bilateral hyperalgesia and reduced vibratory sensation were found distal to the ankle joints. Light-touch and position senses were intact. The strengths of bilateral wrist flexion, bilateral grip and finger extension/flexion, bilateral plantar dorsiflexion, and all proximal limbs were grades 4+, 4, 4, and 5, respectively. Her tendon reflexes and muscle tone were decreased. A negative Romberg sign and clumsy rapidly alternating hand movements were observed. Bilateral finger-to-nose and heel-to-shin tests were abnormal. No pyramidal sign was observed.

Magnetic resonance imaging (MRI) demonstrated high-intensity T2-weighted lesions in the white matter of the temporal pole and the periventricular region (Fig. 1A). MRI also showed prominent cerebellar atrophy, which had deteriorated from 2018 to 2022 (Fig. 1B-D). Consistent with the MRI findings, in 2018 the patient starting developing unsteadiness and slurred speech, but she could still walk with assistance and engage in communication. However, by 2022 she had lost the ability to walk and communicate.

The Mini-Mental State Examination (19 points) and Montreal Cognitive Assessment (12 points) revealed impaired cognition. A nerve conduction velocity study revealed polyneuropathy mainly involving the sensory and motor axons. Electromyography indicated myogenic damage and myotonia potentials in multiple muscles. Electronystagmography revealed damage to the cerebellum and its related fibers. Genetic sequencing revealed the abnormal expansion of a CTG triplet repeat in the noncoding region of the DMPK gene (135 copies). However, we could not obtain genetic data for her younger brother. Based on genetic findings, the patient was diagnosed with DM1.

Manifestations supporting a diagnosis of multiple-system atrophy (MSA) or other neurodegenerative diseases were not found. Whole-exome sequencing did not reveal other pathogenic mutations. Repeat expansions associated with spinocerebellar ataxia were examined in genes including ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATXN8, PPP2R2B, TBP, ATN1, FXN, ATXN10, and NOP56, but no abnormality was found.

Neuroimaging abnormalities of DM1 are mainly found in the frontal and anterior temporal lobes, including cortical atrophy and subcortical white-matter hyperintensities.23 Previous Southern blot analyses of autopsy brain tissues revealed abnormal amplification of CTG in the cerebellum of patients with DM1.45 It was also found that toxic effects of RNA mediated by mutant genes can lead to abnormal discharges of Bergman’s glial cells and Purkinje cells in the cerebellum of DM1 mice.6 However, few previous studies have found clinical and neuroimaging manifestations of cerebellar degeneration in DM1 patients.3

There have been previous case reports of patients diagnosed with both DM1 and spinocerebellar ataxia.78 However, further genetic analysis of the present case revealed no other possible causative genetic variants except for DMPK. In addition, there is a case report of a patient with DM1 who developed vertical eye movement and posture adjustment disorders that was ultimately confirmed as progressive supranuclear palsy through autopsy.9 MSA is the most common neurodegenerative disease with prominent cerebellar degeneration.10 However, no other manifestations were found in the present case to support the diagnosis of MSA. Consideration should also be given to paraneoplastic cerebellar degeneration. However, our patient had been symptomatic for over 4 years, and no evidence of an underlying tumor was found. Meanwhile, the presence of similar symptoms in the patient’s younger brother could not be attributed to neurodegenerative diseases or paraneoplastic cerebellar degeneration. Additionally, severe peripheral neuropathy can also lead to ataxia. Despite evidence of peripheral neuropathy in this patient, her negative Romberg sign and electronystagmography findings all suggested cerebellar involvement.

In conclusion, we consider that the cerebellar degeneration in this patient was caused by DM1, although other unknown rare causes cannot be completely excluded. Given that DM is a disease with multisystem involvement, future studies should focus more on changes in the central nervous system and its possible underlying mechanisms.

Acknowledgments

The authors thank the patient and his family, nurses, and support staff involved in the care of this patient.

Availability of Data and Material

The data sets generated or analyzed during the study are available from the corresponding author upon reasonable request.

Fig. 1 Brain magnetic resonance imaging of the patient. A: T2-weighted sequences showing white-matter hyperintensities in the corona radiata and periventricular region (a) and in the anterior temporal lobes (b). B–D: T1-weighted sagittal (a) and axial (b) sequences showing atrophy throughout the cerebellum, which had deteriorated from 2018 (B) to 2019 (C) to 2022 (D).

Ethics Statement: This study was approved by the Institutional Review Board and Ethics Committee at Peking University First Hospital (2019-181). Written informed consent was obtained from the patient in this study.

Author Contributions: Conceptualization: Chen Ling, Yunchuang Sun.

Supervision: Yunchuang Sun.

Visualization: Chen Ling, Yiming Zheng, Yunchuang Sun.

Writing—original draft: Chen Ling, Jianchun Wang, Yunchuang Sun.

Writing—review & editing: all authors.

Conflicts of Interest: The authors have no potential conflicts of interest to disclose.

Funding Statement: This work was supported by the National Natural Science Foundation of China (82101355, 82201550).
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