Hereditary motor and sensory neuropathy Okinawa type mimicking proximal myopathy.

Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P), or, Okinawa type, is a rare neuromuscular disorder characterized by proximal dominant neurogenic atrophy and distal sensory alterations with an autosomal dominant inheritance pattern. We present a case of a Brazilian woman of Okinawan ancestry, with symmetrical proximal weakness, fasciculations, absent patellar reflexes and positive familial history for the same symptoms. These findings led to genetic testing, which identified a variant in the TFG gene (c.854 C>T;p.(Pro285Leu), confirming the diagnosis of HMSN-P. HMSN-P seemed to be restricted to populations in Okinawa, however, other HMSN-P cases were described in several parts of the world, especially in South America. This case report emphasizes the importance of considering HMSN-P in patients presenting with clinical features resembling proximal myopathy, especially in individuals with Okinawan ancestry.

The Role of MRI in Differentiating Demyelinating and Inflammatory (not Infectious) Myelopathies.

Demyelinating and inflammatory myelopathies represent a group of diseases with characteristic patterns in neuroimaging and several differential diagnoses. The main imaging patterns of demyelinating myelopathies (multiple sclerosis, neuromyelitis optica spectrum disorder, acute disseminated encephalomyelitis, and myelin oligodendrocyte glycoprotein antibody-related disorder) and inflammatory myelopathies (systemic lupus erythematosus-myelitis, sarcoidosis-myelitis, Sjögren-myelitis, and Behçet's-myelitis) will be discussed in this article, highlighting key points to the differential diagnosis.

Transcriptome analyses of the cortex and white matter of focal cortical dysplasia type II: Insights into pathophysiology and tissue characterization.

Introduction: Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant epilepsy. According to the 2022 International League Against Epilepsy classification, FCD type II is characterized by dysmorphic neurons (IIa and IIb) and may be associated with balloon cells (IIb). We present a multicentric study to evaluate the transcriptomes of the gray and white matters of surgical FCD type II specimens. We aimed to contribute to pathophysiology and tissue characterization. Methods: We investigated FCD II (a and b) and control samples by performing RNA-sequencing followed by immunohistochemical validation employing digital analyses. Results: We found 342 and 399 transcripts differentially expressed in the gray matter of IIa and IIb lesions compared to controls, respectively. Cholesterol biosynthesis was among the main enriched cellular pathways in both IIa and IIb gray matter. Particularly, the genes HMGCS1, HMGCR, and SQLE were upregulated in both type II groups. We also found 12 differentially expressed genes when comparing transcriptomes of IIa and IIb lesions. Only 1 transcript (MTRNR2L12) was significantly upregulated in FCD IIa. The white matter in IIa and IIb lesions showed 2 and 24 transcripts differentially expressed, respectively, compared to controls. No enriched cellular pathways were detected. GPNMB, not previously described in FCD samples, was upregulated in IIb compared to IIa and control groups. Upregulations of cholesterol biosynthesis enzymes and GPNMB genes in FCD groups were immunohistochemically validated. Such enzymes were mainly detected in both dysmorphic and normal neurons, whereas GPNMB was observed only in balloon cells. Discussion: Overall, our study contributed to identifying cortical enrichment of cholesterol biosynthesis in FCD type II, which may correspond to a neuroprotective response to seizures. Moreover, specific analyses in either the gray or the white matter revealed upregulations of MTRNR2L12 and GPNMB, which might be potential neuropathological biomarkers of a cortex chronically exposed to seizures and of balloon cells, respectively.