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ALS-plus related clinical and genetic study from China

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Abstract

Background

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. An increasing number of researchers have found extra motor features in ALS, which are also called ALS-plus syndromes. Besides, a great majority of ALS patients also have cognitive impairment. However, clinical surveys of the frequency and genetic background of ALS-plus syndromes are rare, especially in China.

Methods

We investigated a large cohort of 1015 patients with ALS, classifying them into six groups according to different extramotor symptoms and documenting their clinical manifestations. Meanwhile, based on their cognitive function, we divided these patients into two groups and compared demographic characteristics. Genetic screening for rare damage variants (RDVs) was also performed on 847 patients.

Results

As a result, 16.75% of patients were identified with ALS-plus syndrome, and 49.5% of patients suffered cognitive impairment. ALS-plus group had lower ALSFRS-R scores, longer diagnostic delay time, and longer survival times, compared to ALS pure group. RDVs occurred less frequently in ALS-plus patients than in ALS-pure patients (P = 0.042) but showed no difference between ALS-cognitive impairment patients and ALS-cognitive normal patients. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus symptoms than ALS-cognitive normal group (P = 0.001).

Conclusion

In summary, ALS-plus patients in China are not rare and show multiple differences from ALS-pure patients in clinical and genetic features. Besides, ALS-cognitive impairment group tends to harbour more ALS-plus syndrome than ALS-cognitive normal group. Our observations correspond with the theory that ALS involves several diseases with different mechanisms and provide clinical validation.

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Acknowledgements

We are grateful to the participating patients for their involvement. We would like to thank the patients for permitting us to publish this information.

Data sharing and data accessibility

The original contributions presented in the study are included in the article/Supplementary material; further inquiries can be directed to the corresponding authors.

Funding

This work was supported by the Science and Technology Innovation 2030 (STI2030-Major Projects:2021ZD0201803 to J. W.); the National Key R&D Program of China (#2021YFA0805202 and #2018YFC1312003 to J. W; 2018YFC2000300 to X. Z); National Natural Science Foundation of China (#82171431, 81671120 and 81300981 to J. W.); the Natural Science Fund for Distinguished Young Scholars of Hunan Province, China (#2020JJ2057 to J. W.) and the Project Program of National Clinical Research Center for Geriatric Disorders at Xiangya Hospital (#2020LNJJ13 to J. W.).

Author information

Author notes

  1. Cheng Chang and Qianqian Zhao contributed equally to this work. Xuewei Zhang and Junling Wang jointly supervised this work.

Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, People’s Republic of China

    Cheng Chang, Qianqian Zhao, Pan Liu, Yanchun Yuan, Zhen Liu, Yiting Hu, Wanzhen Li, Xiaorong Hou, Xuxiong Tang, Bin Jiao, Jifeng Guo, Lu Shen, Hong Jiang, Beisha Tang & Junling Wang

  2. Health Management Center, Xiangya Hospital, Central South University, Changsha, People’s Republic of China

    Cheng Chang & Xuewei Zhang

  3. Department of Neurology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China

    Cheng Chang

  4. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Bin Jiao, Jifeng Guo, Lu Shen, Beisha Tang & Junling Wang

  5. Hunan International Scientific and Technological Cooperation Base of Neurodegenerative and Neurogenetic Diseases, Changsha, People’s Republic of China

    Bin Jiao, Jifeng Guo, Lu Shen, Hong Jiang, Beisha Tang & Junling Wang

  6. Engineering Research Center of Hunan Province in Cognitive Impairment Disorders, Central South University, Changsha, China

    Bin Jiao, Jifeng Guo, Lu Shen, Hong Jiang, Beisha Tang & Junling Wang

  7. National Clinical Research Center for Geriatric Diseases, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China

    Bin Jiao, Jifeng Guo, Lu Shen, Hong Jiang, Beisha Tang & Junling Wang

  8. School of Basic Medical Science, Central South University, Changsha, Hunan, People’s Republic of China

    Hong Jiang

Authors
  1. Cheng Chang
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  2. Qianqian Zhao
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  3. Pan Liu
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Contributions

C. C., Q. Z., P. L., L. S., J. G., B. T., J. W. and X. Z. contributed to the conception and design of the study; X. T., Z. L., W. L., Y. H., H. J., Y. Y., X. H. and B. J. contributed to the acquisition and analysis of the data; C. C., Q. Z., P. L., Y. Y., Z. L., X. Z. and J. W. contributed to the drafting of the manuscript and in preparing the figures.

Corresponding author

Correspondence to Junling Wang.

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Ethics approval and consent to participate

Written informed consent was obtained from all the participants and the study protocol was approved by the Ethics Committee and the Expert Committee of Xiangya Hospital, Central South University; the number of the approval is 202106134.

Conflict of interest

The authors declare no competing interests.

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Supplementary information

Supplementary file 1

Supplemental Figure 1 The frequency of different gene mutations in the ALS-pure or ALS-plus group.

Supplementary file 2

Supplemental Figure 2 The frequency of different gene mutations in the ALS-cognitive normal or ALS-cognitive impairment group.

Supplementary file 3

Supplemental Table 1 Logistic analysis between the ALS-pure and ALS-plus groups.

Supplementary file 4

Supplemental Table 2 RDVs and demographic characteristics in the ALS-pure and ALS-plus groups.

Supplementary file 5

Supplemental Table 3 Rare disease variants (RDVs) of PD-related gene in the ALS-pure and ALS-plus groups.

Supplementary file 6

Supplemental Table 4 Ratio of comorbidity among ALS subgroups.

Supplementary file 7

Supplemental Table 5 Cox analysis about factors associated with survival in ALS patients

Supplementary file 8

Supplemental Table 6 RDVs and demographic characteristics in the ALS-cognitive impairment and ALS-cognitive normal groups.

Supplementary file 9

Supplemental Table 7 Logistic analysis between the ALS-cognitive impairment and ALS-cognitive normal groups.

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Chang, C., Zhao, Q., Liu, P. et al. ALS-plus related clinical and genetic study from China. Neurol Sci 44, 3557–3566 (2023). https://doi.org/10.1007/s10072-023-06843-4

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