The investigation of genetic and clinical features in patients with hereditary spastic paraplegia in central-Southern China.

OBJECTIVE: Hereditary spastic paraplegias (HSP) is a clinically and genetically heterogeneous group of neurodegenerative disorders. We describe the genetic and clinical features of a cohort of five HSP families from central-southern China. METHODS: Using targeted exome-sequencing technology, we investigated the genetic and clinical features in five HSP families. We reviewed the clinical histories of these patients as well as the molecular and functional characterization of the associated gene variants. We also performed functional analysis of an intron variant of SPAST in vitro. RESULTS: We identified a known SPAST mutation (p.Pro435Leu) in a family with autosomal dominant HSP (AD-HSP) and four novel variants in two HSP families and a sporadic case. These identified four novel variants included a variant in SPG11 (p.Val1979Ter), two variants in B4GALNT1 (p.Ser475Phe and c.1002 + 2 T > G), and a splicing site variant in SPAST (c.1245+5G>A). Minigene analysis of the splicing variant in SPAST (c.1245+5G>A) revealed that the mutation resulted in mRNAs with a loss of exon 9. The SPG4 family carrying c.1245+5G>A variant in SPAST exhibited genetic anticipation, with a decreased age at onset and increased severity in successive generations. The proband with p.Val1979Ter variant in SPG11 showed characteristic clinical features of early-onset, severe spasticity, and corpus callosum atrophy which were highly suggestive of the diagnosis of SPG11-associated HSP. CONCLUSIONS: Our findings strongly support variable phenotype of B4GALNT1-related SPG26 and also expand the clinical and mutation spectrum of HSP caused by mutations in SPAST, SPG11, and B4GALNT1. These results will help to improve the efficiency of early diagnosis in patients clinically suspected of HSP.

Temporal changes of CT findings between non-severe and severe cases of COVID-19 pneumonia: a multi-center, retrospective, longitudinal Study.

Background and aim: To perform a longitudinal analysis of serial CT findings over time in patients with COVID-19 pneumonia. Methods: From February 5 to March 8, 2020, 73 patients (male to female, ratio of 43:30; mean age, 51 years) with COVID-19 pneumonia were retrospectively enrolled and followed up until discharge from three institutions in China. The patients were divided into the severe and non-severe groups according to treatment option. The patterns and distribution of lung abnormalities, total CT scores, single ground-glass opacity (GGO) CT scores, single consolidation CT scores, single reticular CT scores and the amounts of zones involved were reviewed by 2 radiologists. These features were analyzed for temporal changes. Results: In non-severe group, total CT scores (median, 9.5) and the amounts of zones involved were slowly increased and peaked in disease week 2. In the severe group, the increase was faster, with scores also peaking at 2 weeks (median, 20). In both groups, the later parameters began to decrease in week 4 (median values of 9 and 19 in the non-severe and severe groups, respectively). In the severe group, the dominant residual lung lesions were reticular (median single reticular CT score, 10) and consolidation (median single consolidation CT score, 7). In the non-severe group, the dominant residual lung lesions were GGO (median single GGO CT score, 7) and reticular (median single reticular CT score, 4). In both non-severe and severe groups, the GGO pattern was dominant in week 1, with a higher proportion in the severe group compared with the non-severe group (72% vs. 65%). The consolidation pattern peaked in week 2, with 9 (32%) and 19 (73%) in the non-severe and severe groups, respectively; the reticular pattern became dominant from week 4 (both group >40%). Conclusion: The extent of CT abnormalities in the severe and non-severe groups peaked in disease week 2. The temporal changes of CT manifestations followed a specific pattern, which might indicate disease progression and recovery.

Fangcang Shelter Hospital in Wuhan: A radiographic report on a cohort of 98 COVID-19 patients.

Objectives: To present the temporal changes of CT manifestations in COVID-19 patients from a single fangcang shelter hospital and to facilitate the understanding of the disease course. Materials and Methods: This retrospective study included 98 patients (males: females, 43:55, mean year, 49±12 years) with confirmed COVID-19 at Jianghan fangcang shelter hospital admitted between Feb 05, 2020, and Feb 09, 2020, who had initial chest CTs at our hospital. Radiographic features and CT scores were analyzed. Results: A total of 267 CT scans of 98 patients were evaluated. Our study showed a high median total CT score of 7 within the first week from symptom onset, peaked in the 2nd week at 10, followed by persistently high levels of CT score with 9.5, 7 and 7 for the week 3, 4, and >4, respectively, and a prolonged median disease course (30 days, the median interval between the onset of initial symptoms and discharge). Ground-glass opacity (GGO) (58%, 41/71) was the earliest and most frequent finding in week 1. Consolidation (26%, 14/53) and mixed pattern (40%, 21/53) were predominant patterns in 2nd week. GGO and reticular were the main patterns of later phase CT scans in patients with relatively advanced diseases who had longer illness duration (≥4 weeks). Among the 94 CT abnormalities obtained within 3 days from the twice RT-PCR test turned negative, the mixed pattern was mainly presented in patients with disease duration of 2-3 weeks, for GGO and reticular were common during the whole course. Conclusion: Discharged patients from fangcang shelter hospital demonstrated a high extent of lung abnormalities on CT within the first week from symptom onset, peaked at 2nd week, followed by persistence of high levels and a prolonged median disease course. GGO was the predominant pattern in week 1, consolidation and mixed pattern in 2nd week, whereas GGO and reticular patterns in later stages (≥4 weeks).