Phenotypic spectrum of iron-sulfur cluster assembly gene IBA57 mutations: c.286 T > C identified as a hotspot mutation in Chinese patients with a stable natural history.

Mutations in IBA57 disrupt iron-sulfur clusters maturation, causing a rare mitochondrial disease. Clinical manifestations vary from neonatal lethality to childhood-onset spastic paraparesis, yet the ethnic heterogeneity and natural history remain unclear, necessitating further exploration. This study aimed to delineate the genotype-phenotype correlation of IBA57 mutations by analyzing diverse clinical presentations. We report 11 Chinese patients and include literature-reported cases, totaling 61 patients enrolled for analysis. Clinical, neuroimaging, genetic, and disease progression information were collected. Among these, 46 presented as multiple mitochondrial dysfunctions syndrome 3 (MMDS3), with 58.7% originating from Chinese population. Based on disease course, we propose three clinical subtypes: neonatal, infant and childhood subtypes. Neonatal cases universally displayed hypotonia and respiratory distress at presentation, deceased within three months. Most infancy and childhood cases exhibited developmental regression and impaired motor function. Cavitating leukoencephalopathy was a typical neuroimaging finding in MMDS3 patients. The c.286 T > C mutation was reported in 85.2% of Chinese patients. A significantly lower mortality rate was observed compared to the non-Chinese group (P = 0.002), with a survival rate exceeding 90% at 5 years, indicating a relatively stable disease progression. Fifteen cases from three families manifested the spastic paraplegia 74 phenotype, demonstrating normal development before onset, with common clinical manifestations including spastic paraplegia (14/15), visual impairment (10/13), and peripheral neuropathy (9/13). In conclusion, this study indicates a hotspot mutation in Chinese and analyses the disease progression with different clinical subtypes.

Abnormal intrinsic functional hubs and connectivity in patients with post-stroke depression.

OBJECTIVE: The present study aimed to investigate the specific alterations of brain networks in patients with post-stroke depression (PSD), and further assist in elucidating the brain mechanisms underlying the PSD which would provide supporting evidence for early diagnosis and interventions for the disease. METHODS: Resting-state functional magnetic resonace imaging data were acquired from 82 nondepressed stroke patients (Stroke), 39 PSD patients, and 74 healthy controls (HC). Voxel-wise degree centrality (DC) conjoined with seed-based functional connectivity (FC) analyses were performed to investigate the PSD-related connectivity alterations. The relationship between these alterations and depression severity was further examined in PSD patients. RESULTS: Relative to both Stroke and HC groups, (1) PSD showed increased centrality in regions within the default mode network (DMN), including contralesional angular gyrus (ANG), posterior cingulate cortex (PCC), and hippocampus (HIP). DC values in contralesional ANG positively correlated with the Patient Health Questionnaire-9 (PHQ-9) scores in PSD group. (2) PSD exhibited increased connectivity between these three seeds showing altered DC and regions within the DMN: bilateral medial prefrontal cortex and middle temporal gyrus and ipsilesional superior parietal gyrus, and regions outside the DMN: bilateral calcarine, ipsilesional inferior occipital gyrus and contralesional lingual gyrus, while decreased connectivity between contralesional ANG and contralesional supramarginal gyrus. Moreover, these FC alterations could predict PHQ-9 scores in PSD group. INTERPRETATION: These findings highlight that PSD was related with increased functional connectivity strength in some areas within the DMN, which might be attribute to the specific alterations of connectivity between within DMN and outside DMN regions in PSD.

Functional network reorganization after endovascular thrombectomy in patients with anterior circulation stroke.

BACKGROUND: Endovascular thrombectomy has been confirmed to be an effective therapy for acute ischemic stroke (AIS). However, how functional brain networks reorganize after restoration of blood supply in AIS patients, and whether the degree of reperfusion associates with functional network changes remains unclear. METHODS: Resting-state fMRI data were collected from 43 AIS patients with anterior circulation occlusion after thrombectomy and 37 healthy controls (HCs). Both static and dynamic functional connectivity (FC) within four advanced functional networks including dorsal attention network (DAN), ventral attention network (VAN), executive control network (ECN) and default mode network (DMN), were calculated and compared between post-thrombectomy patients and HCs, and between two subgroups of post-thrombectomy patients with different reperfusion conditions. RESULTS: As compared to HCs, patients showed significant differences in static FC of four functional networks, and in dynamic FC of DAN, ECN and DMN. Furthermore, patients with better reperfusion conditions exhibited increased static FC with precuneus, and altered dynamic FC within precuneus. Moreover, these alterations were associated with clinical assessments of stroke severity and functional recovery in post-thrombectomy patients. CONCLUSIONS: Collectively, these findings may provide the potential imaging markers for assessment of thrombectomy efficacy and help establish the specific rehabilitation treatments for post-thrombectomy patients.