Isolated Paravermal Hyperintensities in Neuronal Intranuclear Inclusion Disease

Abstract

A 69-year-old woman without a remarkable family history presented with a 5-year history of dizziness and gait difficulty. Neurologic examinations revealed saccadic eye movement and mild limb and truncal ataxia. She had tremor, hyporeflexia, and miosis. Fluid-attenuated inversion recovery images showed isolated bilateral paravermal hyperintensities1 (Figure). Skin biopsy demonstrated eosinophilic intranuclear inclusions positive for ubiquitin and p62 in the adipocytes and sweat gland cells. Expanded CGG repeats in NOTCH2NLC2 lead to the diagnosis of neuronal intranuclear inclusion disease (NIID). Corticomedullary lesions are sometimes absent in the early stages of NIID and isolated paravermal hyperintensities can be the initial radiologic findings.

Recent advances in CGG repeat diseases and a proposal of fragile X-associated tremor/ataxia syndrome, neuronal intranuclear inclusion disease, and oculophryngodistal myopathy (FNOP) spectrum disorder

“…(3) Core features include leukoencephalopathy, neuropathy, and oculopharyngeal-type myopathy. MRI findings share similar findings such as MCP signs [7], paravermal hyperintensities [39][40][41], or diffusion hyperintensities in the corticomedullary junction [7,17,41] in addition to white matter changes in the cerebrum. However, there is substantial interfamilial and intrafamilial variability in clinical status and neuroradiological findings [40].…”

“…Leukoencephalopathy and diffusion hyperintensity in the corticomedullary junction are characteristic findings in brain MRI. MCP signs are also observed [ 7 ], and paravermal hyperintensity is another neuroradiological finding in NIID1 [ 39 , 40 ], all of which are found in FXTAS [ 41 ]. Reflecting peripheral neuropathy, slowing of motor and sensory nerve velocities with or without decreased amplitudes of compound muscle action potentials or sensory nerve action potentials are also frequently observed.…”

“…MRI findings share similar findings such as MCP signs [ 7 ], paravermal hyperintensities [ 39 – 41 ], or diffusion hyperintensities in the corticomedullary junction [ 7 , 17 , 41 ] in addition to white matter changes in the cerebrum. However, there is substantial interfamilial and intrafamilial variability in clinical status and neuroradiological findings [ 40 ]. (4) Ubiquitin- or p62-positive inclusions are a pathological hallmark.…”

Unraveling rare form of adult-onset NIID by characteristic brain MRI features: A single-center retrospective review

“…In our study, all patients had Fazekas grade 2 or 3 confluent white matter hyperintensity throughout the entire lobes and the corpus callosum, internal and external capsule, thalamus, basal ganglia, and middle cerebellar peduncles consistent with previous studies ( 11 , 20 , 33 ). Isolated paravermal hyperintensities on T2WI/FLAIR were reported to be the initial radiologic findings in NIID patients ( 34 ). We also found additional involvement on T2WI/FLAIR of the pons that was not previously well-reported, suggesting that extensive white matter lesions in the cerebral hemispheres brainstem and cerebellum can be involved in NIID.…”

Clinical and neuroimaging review of triplet repeat diseases

“…The paravermal FLAIR hyperintensity (paravermal sign) is frequently observed in NIID [19]. It is worth noting that paravermal sign can appear before other imaging findings and be the only neuroimaging clue to NIID diagnosis [98][99][100]. The MCP sign can also be observed in NIID.…”