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Neuronal intranuclear inclusion disease with cortical involvement in left hemisphere: a case report

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Summary

Background

Neuronal intranuclear inclusion disease (NIID) is a rare highly heterogeneous disease. In this paper, we present a case of NIID featured in cortical involvement in left hemisphere of brain and the imaging changes in the process of the disease.

Case presentation

A 57-year-old female was hospitalized due to recurrent attacks of headache with cognitive impairment and tremor for 2 years. The symptoms of headache episodes were reversible. The characteristic radiologic change was high intensity signal involving the grey matter-white matter junction on the brain diffusion-weighted imaging (DWI), which existed in the frontal lobe and then extended backwards. Atypical features on fluid-attenuated inversion recovery (FLAIR) sequences showing small patchy high signals in the cerebellar vermis. High signals and edema were detected on FLAIR images along the cortex of the left occipito-parieto-temporal lobes, expanding and gradually shrinking in the follow-up visit. Besides, cerebral atrophy and bilateral symmetrical leukoencephalopathy were also detected. Skin biopsy and genetic testing confirmed the diagnosis of NIID.

Conclusion

Except for typical radiological change strongly suggesting NIID, it is also necessary to notice the insidious symptoms of NIID combining with some atypical imaging features to make an early diagnosis. Skin biopsies or genetic testing should be carried out early in patients with highly suspected NIID.

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References

  1. Sone J, Kitagawa N, Sugawara E, et al. Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed via skin biopsy. J Neurol Neurosurg Psychiatry. 2014;85(3):354–6. https://doi.org/10.1136/jnnp-2013-306084.

    Article  PubMed  Google Scholar 

  2. Sone J, Mori K, Inagaki T, et al. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain. 2016;139(Pt 12):3170–86. https://doi.org/10.1093/brain/aww249.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Liang H, Wang B, Li Q, et al. Clinical and pathological features in adult-onset NIID patients with cortical enhancement. J Neurol. 2020;267(11):3187–98. https://doi.org/10.1007/s00415-020-09945-7.

    Article  PubMed  Google Scholar 

  4. Sugiyama A, Sato N, Kimura Y, et al. MR imaging features of the cerebellum in adult-onset neuronal Intranuclear inclusion disease: 8 cases. AJNR Am J Neuroradiol. 2017;38(11):2100–4. https://doi.org/10.3174/ajnr.A5336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lindenberg R, Rubinstein LJ, Herman MM, Haydon GB. A light and electron microscopy study of an unusual widespread nuclear inclusion body disease. A possible residuum of an old herpesvirus infection. Acta Neuropathol. 1968;10(1):54–73. https://doi.org/10.1007/BF00690510.

    Article  CAS  PubMed  Google Scholar 

  6. Sone J, Tanaka F, Koike H, et al. Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease. Neurology. 2011;76(16):1372–6. https://doi.org/10.1212/WNL.0b013e3182166e13.

    Article  CAS  PubMed  Google Scholar 

  7. Sone J, Mitsuhashi S, Fujita A, et al. Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nat Genet. 2019;51(8):1215–21. https://doi.org/10.1038/s41588-019-0459-y.

    Article  CAS  PubMed  Google Scholar 

  8. Ma D, Tan YJ, Ng ASL, et al. Association of NOTCH2NLC repeat expansions with parkinson disease. JAMA Neurol. 2020;77(12):1559–63. https://doi.org/10.1001/jamaneurol.2020.3023.

    Article  PubMed  Google Scholar 

  9. Fang P, Yu Y, Yao S, et al. Repeat expansion scanning of the NOTCH2NLC gene in patients with multiple system atrophy. Ann Clin Transl Neurol. 2020;7(4):517–26. https://doi.org/10.1002/acn3.51021.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sun QY, Xu Q, Tian Y, et al. Expansion of GGC repeat in the human-specific NOTCH2NLC gene is associated with essential tremor [published correction appears in Brain. 2020 Mar 1;143(3):e24. Brain. 2020;143(1):222–33. https://doi.org/10.1093/brain/awz372.

    Article  PubMed  Google Scholar 

  11. Jiao B, Zhou L, Zhou Y, et al. Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias. Neurobiol Aging. 2020;89:142.e1–142.e7. https://doi.org/10.1016/j.neurobiolaging.2020.01.010.

    Article  CAS  PubMed  Google Scholar 

  12. Ariza J, Rogers H, Monterrubio A, Reyes-Miranda A, Hagerman PJ, Martínez-Cerdeño V. A majority of FXTAS cases present with Intranuclear inclusions within Purkinje cells. Cerebellum. 2016;15(5):546–51. https://doi.org/10.1007/s12311-016-0776-y.

    Article  CAS  PubMed  Google Scholar 

  13. Hagerman PJ, Hagerman RJ. Fragile X‑associated tremor/ataxia syndrome. Ann N Y Acad Sci. 2015;1338(1):58–70. https://doi.org/10.1111/nyas.12693.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Boivin M, Willemsen R, Hukema RK, Sellier C. Potential pathogenic mechanisms underlying Fragile X Tremor Ataxia Syndrome: RAN translation and/or RNA gain-of-function? Eur J Med Genet. 2018;61(11):674–9. https://doi.org/10.1016/j.ejmg.2017.11.001.

    Article  PubMed  Google Scholar 

  15. Abe K, Fujita M. Over 10 years MRI observation of a patient with neuronal intranuclear inclusion disease. BMJ Case Rep. 2017;2017(2017):bcr2016218790. https://doi.org/10.1136/bcr-2016-218790.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yokoi S, Yasui K, Hasegawa Y, et al. Pathological background of subcortical hyperintensities on diffusion-weighted images in a case of neuronal intranuclear inclusion disease. Clin Neuropathol. 2016;35(6):375–80. https://doi.org/10.5414/NP300961.

    Article  PubMed  Google Scholar 

  17. Yu WY, Xu Z, Lee HY, et al. Identifying patients with neuronal intranuclear inclusion disease in Singapore using characteristic diffusion-weighted MR images. Neuroradiology. 2019;61(11):1281–90. https://doi.org/10.1007/s00234-019-02257-2.

    Article  PubMed  Google Scholar 

  18. El-Hattab AW, Adesina AM, Jones J, Scaglia F. MELAS syndrome: Clinical manifestations, pathogenesis, and treatment options. Mol Genet Metab. 2015;116(1–2):4–12. https://doi.org/10.1016/j.ymgme.2015.06.004.

    Article  CAS  PubMed  Google Scholar 

  19. Okamura S, Takahashi M, Abe K, Inaba A, Sone J, Orimo S. A case of neuronal intranuclear inclusion disease with recurrent vomiting and without apparent DWI abnormality for the first seven years. Heliyon. 2020;6(8):e4675. https://doi.org/10.1016/j.heliyon.2020.e04675.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Raza HK, Singh S, Rai P, et al. Recent progress in neuronal intranuclear inclusion disease: a review of the literature. Neurol Sci. 2020;41(5):1019–25. https://doi.org/10.1007/s10072-019-04195-6.

    Article  PubMed  Google Scholar 

  21. Yu J, Liufu T, Zheng Y, et al. CGG repeat expansion in NOTCH2NLC causes mitochondrial dysfunction and progressive neurodegeneration in Drosophila model. Proc Natl Acad Sci U S A. 2022;119(41):e2208649119. https://doi.org/10.1073/pnas.2208649119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We would like to thank the patient who agreed to publication of this case report. We thank Dr. Yu-hong Qin (from the Department of Radiology, First Affiliated Hospital of Guangxi Medical University, Nanning, China) for the imaging evaluation of this case. We also thank Dr. Zai-qiang Zhang and Dr. Hong-fei Tai (both from the Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China) for the pathological analysis.

Funding

Grant Support: this work was supported by National Natural Science Foundation of China (Grant numbers 82260241), the Natural Science Foundation of Guangxi Province (grant numbers 2015GXNSFAA139171 and 2020GXNSFAA259053), Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2022091), and Guangxi Scholarship Fund of Guangxi Education Department.

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Authors and Affiliations

  1. Department of Neurology, First Affiliated Hospital of Guangxi Medical University, 530021, Nanning, China

    Xiao-ju Wu, Yi-ying Jiang, Li-jie Chen, Guo-qiu Zhou, Dong-can Mo, Liu-yu Liu, Jian-li Li, Xiao-ling Li, Yu-lan Tang & Man Luo M.D., Ph.D.

  2. Guangxi Key Laboratory of Precision Medicine in Cardio-cerebrovascular Diseases Control and Prevention, 530021, Nanning, China

    Man Luo M.D., Ph.D.

  3. Guangxi Clinical Research Center for Cardio-cerebrovascular Diseases, 530021, Nanning, China

    Man Luo M.D., Ph.D.

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  1. Xiao-ju Wu
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  9. Yu-lan Tang
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Corresponding authors

Correspondence to Yu-lan Tang or Man Luo M.D., Ph.D..

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Conflict of interest

X.-j. Wu, Y.-y. Jiang, L.-j. Chen, G.-q. Zhou, D.-c. Mo, L.-y. Liu, J.-l. Li, X.-l. Li, Y.-l. Tang and M. Luo declare that they have no competing interests.

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Ethics approval and consent to participate: not applicable. Consent for publication: written informed consent was obtained from the patient for publication of this case report.

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Xiao-ju Wu and Yi-ying Jiang have contributed equally to this study and should be considered as first co-authors.

Availability of data and material

The datasets supporting the conclusions of this article are included in this article. A video on tremor was attached in the supplementary material.

Supplementary Information

A video on tremor of the case

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Wu, Xj., Jiang, Yy., Chen, Lj. et al. Neuronal intranuclear inclusion disease with cortical involvement in left hemisphere: a case report. Wien Klin Wochenschr 136, 67–72 (2024). https://doi.org/10.1007/s00508-023-02232-1

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