For medical professionals

Neuronal intranuclear inclusion disease (NIID) is an intractable neurodegenerative disease that can cause higher brain dysfunction, peripheral neuropathy, limb muscle weakness, ataxia, and occasionally subacute encephalitic symptoms ^1-6). The first NIID case was reported in 1968 ⁶⁾, and since then NIID had been diagnosed based on common histopathological features, but in 2011, we discovered that NIID can be diagnosed from skin biopsy tissue ⁷⁾. In 2014, we reported that it is possible to make a diagnosis by skin biopsy also in elderly onset cases with abnormal high intensity signals along the cortico-medullary junction in DWI ⁸⁾. As a result, the number of cases diagnosed with NIID has dramatically increased.
In 2019, our research group became the very first in the world to clarify the causative gene of NIID ⁹⁾ as NOTCH2NLC GGC expansion.
Based on these research results, JaNIIDS has been conducting research with the aim of clarifying the pathophysiology of NIID and of developing a radical treatment method. By collecting and analyzing the clinical findings of NIID patients, we target to clarify the natural history and pathophysiology of NIID, along with conducting research at the molecular level such as genes and proteins to develop radical therapeutic methods.

Currently, the following researches are in progress. Please contact the JaNIIDS Secretariat for NIID diagnosis, skin biopsy, genetic testing and research.

• Ministry of Health, Labor and Welfare (MHLW), Research program on rare and intractable diseases
  The research about the establishment of the disease concept and diagnostic criteria of NIID
• The Ministry of Education, Culture, Sports, Science and Technology (MEXT). Grant-in-Aid for Scientific Research (B)
  The study of NIID causative gene and pathophysiology.

Reference

1. Sone J, Mori K, Inagaki T et al. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. Brain;139(12):3170-3186, 2016.
2. Takahashi-Fujigasaki J: Neuronal intranuclear hyaline inclusion disease. Neuropathology, 23(4):351-359. 2003.
3. Patel, H., M. G. Norman, T. L. Perry and K. E. Berry. Multiple system atrophy with neuronal intranuclear hyaline inclusions. Report of a case and review of the literature. J Neurol Sci 67(1): 57-65. 1985.
4. Oyer, C. E., S. Cortez, P. O'Shea and M. Popovic. Cardiomyopathy and myocyte intranuclear inclusions in neuronal intranuclear inclusion disease: a case report. Hum Pathol 22(7): 722-724. 1991.
5. Sone J, Hishikawa N, Koike H et al. :Neuronal intranuclear hyaline inclusion disease showing motor-sensory and autonomic neuropathy. Neurology;65(10):1538-1543, 2005.
6. Lindenberg R, Rubinstein LJ, Herman MM et al. A light and electron microscopy study of an unusual widespread nuclear inclusion body disease. A possible residuum of an old herpesvirus infection. Acta Neuropathol (Berl) , 10(1):54-73.1968.
7. Sone J, Tanaka F, Koike H et al. :Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease. Neurology 76(16): 1372-1376, 2011.
8. Sone J, Kitagawa N, Sugawara E et al.: Neuronal intranuclear inclusion disease cases with leukoencephalopathy diagnosed via skin biopsy. J Neurol Neurosurg Psychiatry; 85(3): 354-6, 2014.
9. Sone J, Mitsuhashi S, Fujita A et al. Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease. Nature Genetics, DOI:10.1038/s41588-019-0459-y. 2019.