Adult-Onset Neuronal Intranuclear Inclusion Disease with Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like (MELAS-like) Episode: A Case Report and Review of Literature

Abstract

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease with highly heterogeneous manifestations. Curvilinear hyperintensity along the corticomedullary junction on diffusion-weighted images (DWI) is a vital clue for diagnosing NIID. DWI hyperintensity tends to show an anterior-to-posterior propagation pattern as the disease progresses. The rare cases of its disappearance may lead to misdiagnosis. Here, we reported a NIID patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like (MELAS-like) episode, and reversible DWI hyperintensities. A review of the literature on NIID with MELAS-like episodes was conducted. A 69-year-old woman stated to our clinics for recurrent nausea/vomiting, mixed aphasia, altered mental status, and muscle weakness for 2 weeks. Neurological examination showed impaired mental attention and reaction capacity, miosis, mixed aphasia, decreased muscle strength in limbs, and reduced tendon reflex. Blood tests were unremarkable. The serological examination was positive for antibody against dipeptidyl-peptidase-like protein 6 (DPPX) (1:32). Brain magnetic resonance imaging (MRI) revealed hyperintensities in the left temporal occipitoparietal lobe on DWI and correspondingly elevated lactate peak in the identified restricted diffusion area on magnetic resonance spectroscopy, mimicking the image of MELAS. Skin biopsy and genetic testing confirmed the diagnosis of NIID. Pulse intravenous methylprednisolone and oral prednisolone were administered, ameliorating her condition with improved neuroimages. This case highlights the importance of distinguishing NIID and MELAS, and reversible DWI hyperintensities can be seen in NIID.

Prevalence and Characterization of NOTCH2NLC GGC Repeat Expansions in Koreans

“… 12 We observed that encephalitis-like episodes were frequently accompanied by headache, fever, and visual disturbances, which have also been observed in previous studies. 30 , 35 - 37 Noticeably, we observed that patients with NIID experiencing encephalitis-like episodes tended to have significantly shorter repeat counts in the expanded alleles than the others ( p = 0.016, Figure 2A ). Despite the marginal p value ( p = 0.06), this negative association between the number of GGC repeats and encephalitis-like episodes was also observed in a Chinese cohort ( n = 247).…”

A comment on a case report about perfusion abnormality in neuronal intranuclear inclusion disease with stroke-like episode

“…A TIA usually goes along without DWI lesions. Only a single NIID patient with a SLL has been previously reported [5] .…”

Adult-Type Neuronal Intranuclear Inclusion Disease with Limb Tremor Onset: Case Report and Literature Review

“…Researchers have proposed several hypotheses regarding the pathogenesis of NIID, including the toxicity of polyamino acid proteins (17)(18)(19), toxic RNA gain-offunction (19,20), and aberrant methylation of GGC repeat sequences (21). Recently, some studies have suggested that dysfunction of ribosome biogenesis and translation and mitochondrial dysfunction might be related to the pathogenesis of NIID (22,23). However, the speci c mechanisms driving the pathogenesis of NIID remain unclear, and extensive experiments in cellular and animal models are required for further studies.…”

“…Advances in the study of disease mechanisms form the basis for the development of preventive and therapeutic interventions. It has been suggested that NIID may be associated with mitochondrial dysfunction; therefore, therapeutic measures for mitochondrial disease may be effective for patients with NIID(23). Yan et al suggested that in ammation might also play an important role in the pathogenesis of NIID(29).…”