A Case Report of Neuronal Intranuclear Inclusion Disease Presenting With Recurrent Migraine-Like Attacks and Cerebral Edema: A Mimicker of MELAS

Abstract

BackgroundNeuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease associated with the GGC repeats in the 5'-untranslated region (5'UTR) of NOTCH2NLC. NIID exhibits a wide range of clinical manifestations. However, patients presenting with recurrent migraine-like attacks and cerebral edema have only rarely been reported.Case PresentationA Chinese female suffered probable migraines with aura for 10 years. At age of 51, aggravating migraine-like attacks co-occurred with a sudden encephalopathy-like episode. Brain MRI showed right cerebral edema and cortical enhancement. Serum lactic acid level was elevated at rest and significantly increased after a simplified serum lactic acid exercise test. The initial diagnosis was MELAS, while NIID was suspected after faint DWI high-intensity signals in the corticomedullary junction was retrospectively recognized. Mitochondrial genome sequencing and gene panel analysis of nuclear genes related to mitochondrial diseases failed to find any causative variants. Repeat-primed PCR and fluorescence amplicon length PCR of NOTCH2NLC gene identified an abnormal expansion of 118 GGC repeats in the 5'UTR of NOTCH2NLC gene.ConclusionNIID should be taken into account for differential diagnosis of migraines and MELAS-like episodes. Besides the corticomedullary hyperintensity on DWI, cortical enhancement in contrast-enhanced brain MRI may also be a brain image marker for the differential diagnosis between MELAS and NIID with MELAS-like episodes.

A case report of neuronal intranuclear inclusion disease with paroxysmal peripheral neuropathy-like onset lacking typical signs on diffusion-weighted imaging

“…The sensory episodes in the present case were distinct from previously reported paroxysmal phenotype which usually involves diffused cortical lesions with unconsciousness, hemiplegia, aphasia, or epileptic seizures (6)(7)(8)(9). Related hyperintensity, edematous areas, and perfusion alterations in the brain imaging have been reported to characterize those typical encephalitic attacks (3).…”

Unraveling the Diagnostic Puzzle: Minor Stroke-Like Lesions and Normal Muscle Histopathology in MELAS Syndrome

“…2,5 In the differential diagnosis of the MELAS syndrome, clinicians should exclude cerebrovascular disease, encephalitis, central nervous system demyelinating diseases, and neuronal intranuclear inclusion disease. 4,6 In addition, differentiation among different subtypes of mitochondrial diseases, such as Leigh syndrome, should also be considered.…”

The polyG diseases: a new disease entity

“…Nevertheless, several studies have indicated that carriers with more than 300 repeats of expanded CGG show a mild or asymptomatic phenotype [ 20 , 127 ]. Beyond NIID, expanded CGG repeats in NOTCH2NLC are occasionally related to a small proportion of Parkinson's disease (PD) [ 65 , 97 , 110 ], multiple system atrophy (MSA) [ 29 ], essential tremor (ET) [ 105 ], degenerative dementia [ 4 , 101 ], ALS [ 46 , 130 ], inherited peripheral neuropathy [ 118 ], distal motor neuropathy [ 122 , 128 ], mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) [ 57 , 123 ], and oculopharyngodistal myopathy (OPDM) [ 127 ]. Intriguingly, CGG expansion in NOTCH2NLC was rarely detected in NIID cases reported in people of Caucasian descent, suggesting that NIID is likely to be genetically heterogeneous among different ethnic groups [ 15 ].…”