神経核内封入体病（neuronal intranuclear inclusion …

1 60 653.. neuronal intranuclear inclusion disease; NIID . 1 *. neuronal intranuclear inclusion disease; NIID . 2011 . 2019 NOTCH2 NLC GGC . NIID MRI DWI . 2 . NIID NIID .. 2020;60:653-662 . Key words NOTCH2 NLC DWI. NIID .. NIID 10 16 . neuronal intranuclear inclusion disease; 2011 NIID . NIID, neuronal intranuclear hyaline inclusion disease; NIHID NIID . intranuclear inclusion body disease; INIBD NIID 2016. 17 . H&E . glia . Schwann . 1 3 Fig. 1 NIID NOTCH2 NLC . p62 GGC 2019 . 18 19 Fig. 3 . 4 6 NIID NIID.. 5 7 NIID . 60 NIID . NIID NIID 1968 Lindenberg . 7 Acta Neuropathologica 1 . NIID . 8 . 7 . 2011 NIID 24 . NIID 9 . 28 . MRI DWI.

2 Fig. 2 . *Corresponding author: 513-8501 3 2 1 .. 1). Received January 14, 2020; Accepted May 22, 2020; Published online in J-STAGE on September 5, 2020 . doi: 60 654 60 10 2020 10 . Fig. 1 Histopathological findings of neuronal intranuclear inclusion disease (NIID). A F: Sporadic NIID, G L: Familial NIID. A: sympathetic ganglion (H&E), B: neuron in temporal lobe (ubiquitin), C: renal tubule cells (ubiquitin), D: astrocyte (EM), E: sweat gland cell of skin (ubiquitin), F: fibroblast of skin (EM), G: dorsal root ganglion neuron (H&E), H: neuron in parietal lobe (ubiquitin), I: Schwann cell (ubiquitin), J: astrocyte (EM), K: fibroblast of skin (ubiquitin), L: fibroblast of skin (EM).

3 Scale bars in A C, E, G I and K = 10 m; in D, F, J and L =1 m. NIID 60 655. Fig. 2 Head MRI findings of neuronal intranuclear inclusion disease (NIID). Both sporadic and familial NIID cases show leukoencephalopathy and DWI high intensity signal in corticomedullary junction. MRI findings of sporadic NIID cases with dementia (A and B) and sporadic NIID cases with weakness (C and D). MRI findings of familial NIID case with dementia at the onset of encephalitic episode (E and F) shows obvious edema in left hemisphere. MRI findings of familial NIID cases with weakness (G and H). T2 weighted image (A, C, E), FLAIR image (G) and DWI (B, D, F and H).

4 1969 Martin . 71 . 20 7 .. 60 656 60 10 2020 10 . Fig. 3 Result of linkage analysis, the position of NOTCH2 NLC gene and GGC repeat. Linkage analysis with maicrosatellite markers shows high LOD score area in wide range of chromosome1 including centromere. Long-read next generation sequencer identified GGC repeat expansion in NOTCH2 NLC exon 1 of isoform 2 and isoform 1 (Orange bar shows the position of GGC repeat). 23 . 3 5 24 . NIID .. Lindenberg . PCR . 1990 . NIID Lindenberg Goutieres NIID . 21 25 11 . Freidreich ataxia . 22 .. NIID 60 657. 7 NIID .. NIID 9 . 10 NIID .. NIID 1990 NOTCH2 NLC . NIID .. H&E . 3 .. NIID NIID .. 2003 Takahashi-Fujigasaki 30 FXTAS Fragile X.

5 NIID NIID premutation tremor/ataxia syndrome 31 32 NIID. 33 . 7 . NIID FXTAS .. NIID . 70 . NIID.. NIID NIID. 25 26 NIID 121 98 . Schwann 27 23 Table 1 . NIID . NIID . 28 .. NIID .. NIID . 38 . 2005 NIID . NIID . NIID 24 . 2011 MRI . NIID NIID . 9 2014 . MRI DWI . NIID . 29 .. 10 cm 30 .. p62 MRI DWI . T2 . DAB .. H&E . Fig. 1E, K mini mental state examination MMSE . 60 658 60 10 2020 10 . Table 1 Summary of neuronal intranuclear inclusion disease (NIID) clinical manifestation. Sporadic NIID total n = 98 Familial NIID total n = 23. Dementia Weakness Dementia Weakness n = 97 n=1 n = 12 n = 11. Diagnosis Skin biopsy 96 ( ) 1 (100%) 11 ( ) 8 ( ).

6 Autopsy 0 (0%) 0 (0%) 3 ( ). Average onset age (range) (42 77) 39 (43 75) (16 39). Average disease duration (range) (1 24) 18 (1 15) (3 44). Sex ratio (male/female) 32/65 0/1 3/9 5/6. Clinical Muscles weakness + 100%. manifestations Sensory disturbance + Autonomic Vomiting impairment Bladder dysfunction Syncope 0% 0%. Miosis 60%. Dementia + 100% Tremor + 0%. Rigidity 0%. Ataxia 0%. Abnormal behavior 0%. Generalized convulsion 0%. Disturbance of consciousness Encephalitic episode 0%. Head-MRI Leukoencephalopathy + 100% 40%. DWI U-fiber high + 100% Ventricular distension + 100% 40%. SPECT Hypo perfusion in cerebral cortex + 100%. Executive function MMSE (<24) 20 0% 0%.

7 Tests FAB (<age matched average) 15 100% 100%. Laboratory Data CK M:>260 IU/l F:>170 IU/l 98 CSF Cell (>5/mm3) 0 0% 0%. Protein (>45 mg/dl) 30 Glucose(<50 mg/dl) 0% 65 0% 0%. HgbA1c (NGSP) ( ) 0% FMR1 premutation 0% 0% 0%. Nerve conduction Motor MCV slowing + 50% 100%. CMAP reduction + 0% Sensory SCV slowing + 50% 100%. SNAP reduction + 25% Except for Diagnosis, Average onset age, Average disease duration and Sex ratio, we described each value as the number of incidence case/ the number of available case (%). About sporadic weakness case, each column showed actual value. We calculated incidence rate(%) for each value with available case number for each item.

8 MCV slowing, SCV slowing, CMAP reduction and SNAP reduction were determined that each value below control average value 2SD. MMSE = mini mental state examination, FAB = frontal assessment battery, NGSP = national glycohemoglobin standardization program, CK = creatine kinase, MCV = motor nerve conduction velocity, CMAP = compound muscle action potential, SCV = sensory nerve conduction velocity, SNAP = sensory nerve action potential. NIID 60 659. frontal assessment battery T2 . FAB . NIID FAB 17 18 29 T2 . 1 DWI . NIID DWI .. NIID NIID . 2 . 16 .. Fig. 2E, F . 17 . DWI . NIID . DWI MRI T2 . 100 NCV DWI . 50 100 NOTCH2 NLC GGC . 81 35 NIID.

9 60 DWI . 100 DWI . MRI NIID . DWI . NIID .. MRI 2005 . DWI NIID 2 DNA . NIID . NIID 400 . 2007 . 20 Mbp Lod Score 4 . NIID Lod Score Fig. 3 . 20 Mbp . NIID . NIID . FXTAS31 32 20 Mbp .. NIID single nucleotide variant; SNV . 33 . NIID . 34 Lod Score NIID . Lod Score . NIID NOTCH2 NLC GGC . FXTAS . FMR1 GCC .. Oxford Nanopore . MRI MinION . NIID . NIID MRI T2 FLAIR NOTCH2 NLC GGC . Fig. 2 18 19 Fig. 3 NOTCH2 NLC . 60 660 60 10 2020 10 . 2013 hg38 .. NIID . NOTCH2 NLC . 36 . DWI . GGC . DWI NIID . Table 1 NIID . NIID NIID NIID . 56 GGC . 225 NIID . 1 61 NIID . 30 61 NIID . 1 . 30 NIID NIID 2019 .. NIID NIID . FXTAS . NIID 47 . NIID NIID.

10 NIID .. COI . 1968 Lindenberg NIID 1 .. H&E . NIID . NIID . Fig. 1 1 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 NIID NIID 1 . herpesvirus infection. Acta Neuropathol (Berl) 1968;10:54-73.. 2 Oyer CE, Cortez S, O ' Shea P, et al. Cardiomyopathy and 5 30 myocyte intranuclear inclusions in neuronal intranuclear 10 30 inclusion disease: a case report. Hum Pathol 1991;22:722-724. 3 Kimber TE, Blumbergs PC, Rice JP, et al. Familial neuronal 17 intranuclear inclusion disease with ubiquitin positive inclusions. NIID J Neurol Sci 1998;160:33-40.