## 4 Discussion  
The principal result of this retrospective explorative study is that in stroke survivors undergoing rehabilitation, higher serum levels of total calcium at baseline significantly predict a better recovery in terms of disability, as measured by the change from baseline of the Barthel Index. This result is in  
Figure 1: Dot plots (with mean values and error bars) of (**A**) total calcium, (**B**) ionized calcium, (**C**) total protein, and (**D**) albumin percentage. Reference ranges are identified by grey areas enclosed by dashed lines. (**E**) Scatterplot of the change from baseline of the Barthel Index (\(\Delta\)BI) after 6 weeks of treatment versus the total calcium at baseline (rho = [PERSON]’s rank-order correlation coefficient). line with the study from [PERSON] et al., which reported that in 659 subjects elevated serum calcium levels measured 72 to 96 h after ischemic stroke predicted a greater independence score on the Barthel Index scale measured 3 months after the acute event [8]. This result was confirmed by the same research group on 237 ischemic stroke patients, evaluated for calcium levels within 24 h from ictus [13]. They found that higher total serum calcium associated with lesser admission stroke severity and better functional outcome at discharge [13]. In our study, although the sample was smaller, we found the same association between serum calcium levels and ability in daily activity before and after 6 weeks of rehabilitation treatment, within 3 months from stroke onset. Moreover, in our group of subacute post-stroke patients calcium levels were almost all into the range of normality, but we found that patients with a higher total calcium profile improved better, probably because these patients had an enhanced general musculoskeletal condition and bone health status. The studies on serum calcium levels and its role in recovery after stroke are very limited; most of the studies are focused on cellular calcium and its involvement in ischemia [14] or on the correlation between levels of calcium and stroke insult [15], as in a very recent study on patients with acute ischemic stroke performed to determine if admission calcium status associated with stroke outcomes after systemic thrombolysis [7]. Further studies probably are necessary to deepen our understanding of this topic and clarify the connection between clinical outcome and biochemical indices of calcium status. For example, in light of the investigation of the general calcium status in patients, it is also important to test Vitamin D, which regulates calcium levels. A very recent meta-analysis showed that Vitamin D serum concentrations--specifically 25(OH) vitamin D--had a positive association with post-stroke recovery [16; 17]. Unfortunately, we did not have the possibility to test 25(OH) vitamin D measurements, which would have better clarified this topic. Another significant result of our study is that in the group of patients analyzed, serum total protein levels and serum albumin percentages were below the reference ranges (Figure 1C,D). It is known that patients with stroke have low compliance regarding the prescribed diet, have poorer eating habits often due to dysphagia, and generally have low dietary quality. An old observational study reported that poor nutritional status on admission predicts poor outcomes after stroke [18]. We did not find a correlation between protein serum levels and recovery outcome, but this result highlights a compromised general nutritional status of patients when admitted to our rehabilitation center. A further study suggested that intensive nutritional supplements improved outcomes in stroke rehabilitation, as assessed with measures of motor function [19]; more recently, a supplementation of amino acids in post-stroke patients has been suggested [20].