Association Between Early Mobilization and Functional Outcomes in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Propensity Score-Matched Study.

BACKGROUND: Early mobilization has been shown to promote functional recovery and prevent complications in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, the efficacy of early mobilization in patients with aSAH remains unclear. This study aimed to investigate the association between early mobilization and functional outcomes in patients with aSAH. METHODS: This multicenter retrospective study was conducted in Japan and included patients with aSAH who received physical therapy with or without occupational therapy from April 2014 to March 2019. The primary outcome was the modified Rankin Scale (mRS) score, with a favorable functional outcome defined as an mRS score of 0-2 and an unfavorable outcome with an mRS score of 3-5. Patients initiating walking training within 14 days of aSAH onset were classified into the early mobilization group, whereas those initiating training after 14 days were classified into the delayed mobilization group. Propensity score matching analysis was performed to assess the association between early mobilization and favorable outcomes. RESULTS: A total of 718 patients were screened, and 450 eligible patients were identified. Before matching, 229 patients (50.9%) were in the early mobilization group and 221 (49.1%) were in the delayed mobilization group. After matching, each group consisted of 122 patients, and the early mobilization group exhibited a higher proportion of favorable outcomes than did the delayed mobilization group (81.1% vs. 52.5%, risk difference 28.7%, 95% confidence interval 17.4-39.9, p < 0.001). CONCLUSIONS: This multicenter retrospective study suggests that initiating walking training within 14 days of aSAH onset is associated with favorable outcomes.

Initiating Mobilization Is Not Associated with Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage: A Retrospective Multicenter Case-control Study.

OBJECTIVE: The study aim was to investigate the association between initiating mobilization within 7 days after onset and symptomatic cerebral vasospasm (SCV) in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: This was a retrospective multicenter case-control study in Japan. Patients with a diagnosis of aSAH who underwent physical therapy with/without occupational therapy were included and categorized into 2 groups according to the presence or absence of SCV. Initiating mobilization was defined as sitting on the bed edge (at least once, with/without assist, regardless of duration) within 7 days after aSAH onset. Cox proportional hazards regression analysis was performed to evaluate the association between initiating mobilization within 7 days after onset and SCV. RESULTS: The analysis included 510 patients. Among all included patients, 57 (11.2%) patients had SCV. In the univariate Cox proportional hazards regression analysis, initiating of mobilization was not associated with SCV (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.45-1.32). In the multivariate analysis, only the modified Fisher scale was significantly associated with SCV (HR = 26.23; 95% CI = 1.21-571.0). CONCLUSION: Initiating mobilization within 7 days after aSAH onset was not associated with SCV in patients with aSAH.

Parental serum alkaline phosphatase activity as an auxiliary tool for prenatal diagnosis of hypophosphatasia.

OBJECTIVE: The objective of this study is to clarify the usefulness of parental alkaline phosphatase (ALP) for prenatal diagnosis of hypophosphatasia (HPP). METHODS: Maternal (m) and paternal (p) ALP values were measured in 77 cases from a multicenter cohort (fetal skeletal dysplasia forum in Japan) of cases with short limbs on ultrasonography during pregnancy. After birth, X-rays, cord blood ALP, and gene analysis were evaluated to achieve an exact diagnosis. The screening usefulness of ALP was examined retrospectively. RESULTS: Seventeen cases were eventually diagnosed as HPP and 60 as not HPP; the overall mean m-ALP and p-ALP (standard deviation) values were 133.4 (53) versus 197 (69) IU/L and 149.6 (71.8) versus 231 (61.4) IU/L (p < 0.001). Receiver operating characteristic curve analysis showed that the optimal m-ALP and p-ALP cutoff values were 123 and 165 IU/L, respectively. Presence of at least one of the m-ALP or p-ALP values abnormally low had a sensitivity, specificity, and positive predictive values of 82% (14/17), 93%, and 78%, respectively, for the diagnosis of HPP. CONCLUSION: Parental ALP measurement might be an auxiliary tool to hone in the prenatal diagnosis of fetal HPP. © 2017 John Wiley & Sons, Ltd.

Perinatal hypophosphatasia caused by uniparental isodisomy.

Hypophosphatasia (HPP) is an inherited disorder characterized by defective bone mineralization caused by mutations in the alkaline phosphatase gene (ALPL). Clinically, the disease spans a great continuum of disease severity and six forms can be distinguished according to the age of onset. The most severe is the autosomal recessive perinatal form, a major prenatal skeletal dysplasia in Japan. The ALPL mutation c.1559delT causes perinatal HPP and occurs frequently in the Japanese. Most patients with perinatal HPP in Japan are homozygous for c.1559delT, and their parents are usually heterozygous with no evidence of consanguinity. Here we identified a fetus with perinatal HPP resulting from an unusual mechanism known as paternal uniparental isodisomy (UPD) of chromosome 1. Sequence analysis of ALPL in the patient revealed the presence of the homozygous mutation c.1559delT. We suspected UPD because the father and mother were heterozygous and wild type, respectively. Analysis of polymorphic microsatellite markers spanning chromosome 1 and whole-genome arrays revealed a uniparental inheritance from the father and excluded deletions or de novo mutations. This is the first description of perinatal HPP caused by UPD. This report also emphasizes the low recurrence risk of a non-Mendelian inheritance pattern in UPD and the value of determining parental genotypes with homozygous mutations in a patient to confirm whether the condition is caused by UPD or not, even when the mutation is detected as a hot spot, as described in the literature.