What is NIID?

What kind of illness is NIID?

NIID: Neuronal Intranuclear Inclusion Disease is an intractable disease which observes foreign substances called "inclusion body" in the "cell nucleus" in the cells of nerve tissues such as the cerebrum, spinal cord, and peripheral nerves and the cells of general organs (Figure1). NIID has been reported to show various symptoms such as forgetfulness and weakness of limbs.
In 2011, we reported the usefulness of skin biopsy for the ante-mortem diagnosis of NIID cases (Figure3), since then, many NIID cases became to be reported by skin biopsy. But there are still many parts to be elucidated because few NIID cases had been diagnosed before the skin biopsy era. Full-scale research aimed at elucidating pathophysiology and development of treatment methods has just begun.

* 1 Inclusion body: Aggregates formed by gathering proteins, etc.

Figure 1

Common symptoms of NIID

Higher brain dysfunction such as forgetfulness and peripheral nerve disorders like weakened muscle strength and sensation of limbs are observed. Patients may also suffer from symptoms such as impairing fine control of limb movements, bladder dysfunction, Parkinson's disease-like tremor, and muscle rigidity. Moreover, some patients may be hospitalized urgently due to symptoms similar to acute encephalitis; headache, fever, and impaired consciousness.

Causes of NIID

As a result of JaNIIDS research, in 2019, the abnormality in the NOTCH2NLC gene was reported as one of the causes of NIID. In the NOTCH2NLC gene, there is a part of the nucleic acid sequence of GGC(Guanine-Guanine-Cytosine) repetition, called GGC repeats. In the case of NIID patients, the number of repetitions of this GGC repeats expanded markedly. However, some research on NIID in western countries reported NIID cases without NOTCH2NLC GGC repeat sequence expansion, so it is speculated that there are other unelucidated causes of NIID besides NOTCH2NLC.

What is the NIID treatment method?

At this time, there is no radical cure. However, it is possible to control the symptoms to some extent with medicine.

How to diagnose NIID?

Imaging tests

For NIID patients, especially those who have symptoms of forgetfulness, white matter encephalopathy (the deep part of the brain appears white as shown in the Figure 2) is observed on brain MRI, and a linear high signal is observed on diffusion weighted image (DWI) (Figure 2).

Figure 2   Brain MRI findings of NIID

Skin biopsy

a small amount of skin on the foot is taken and observed under a microscope. Intranuclear inclusion bodies are observed inside of the cell nucleus of the skin fibroblasts, sweat gland cells and adipocytes (Figure 3).

Figure 3

Genetic test

DNA is extracted from blood, and examined whether the GGC repeat sequence of the NOTCH2NLC gene is extended.