# Vitamin D and Rehabilitation after Stroke: Status of Art
## 5 Vitamin D and Post Stroke Recovery: Focus on Rehabilitation
### Vitamin D and Outcome of Stroke  
Many studies investigated the relationship between Vitamin D levels and general outcome of stroke in post stroke patients, without specifying whether patients underwent rehabilitation treatment. A very recent meta-analysis [11] investigated the prognostic utility of serum 25(OH)D in patients with stroke (ischemic stroke, but not hemorrhagic) in terms of functional outcome, all-cause mortality and recurrence of stroke. Of the 429 articles found, only 11 articles were included which reported all the necessary data. Reported risk estimates with continuous 25(OH)D values were not included. The meta-analysis explored: a. the association of lowest 25(OH)D level with a higher risk of poor functional outcome (five studies; Relative Risk: 1.86; 95% CI 1.16-2.98); b. an increased risk of all-cause mortality (five studies; Relative Risk: 3.56; 95% CI 1.54-8.25). c. the recurrence of stroke (three studies; Relative Risk: 5.49; 95% CI 2.69-11.23). Note that, as the author underlined, the reviewed papers were heterogeneous due to differences in clinical setting, follow-up duration, stages or types of stroke, and only four of them considered the impact of vitamin D deficiency on functional outcome using the modified Rankin scale (a very simple scale used to measure the degree of disability in patients who have had a stroke). [PERSON] et al. [70] reported that patients with lower vitamin D levels at admission showed increased mortality after one year from insult. Another recent study from [PERSON] et al. [71], including 168 acute ischemic stroke patients and 118 controls, reported that patients had lower 25(OH)D levels, with higher frequency of vitamin D deficiency with respect to control. More importantly, 25(OH)D levels had a negative correlation with modified ranking scale after three-months follow-up independently of age, sex and neurological deficit, so Vitamin D deficiency could be deemed as an independent biomarker of ischemic stroke. As for the authors' declaration, some limitations are included in this study, such as the absence of important data including calcium concentration, sun exposure, dietary intake of vitamin D and outdoor physical activity. [PERSON] et al. [14] analyzed the influence of Vitamin D levels on functional outcomes after first-ever ischemic stroke, at 3 months and 6 months from stroke. The functional outcomes were evaluated and  
Figure 2: Role (regulation and modulation) of Vitamin D in neurologic, immunologic, musculoskeletal systems and brain health, that contributes to outcomes in patients with stroke undergoing rehabilitation treatment. measured with the Barthel index and Modified Ranking Scale, including scale of performance in ability of daily living, and neurological disability, respectively. At admission, the NIH Stroke Scale (NIHSS) negatively correlated with vitamin D, suggesting that major impairment after stroke correlated with lower levels of vitamin D; adjusting for age and the baseline NIHSS values, a trend in correlations were found between functional outcomes at all timepoints (Barthel index and modified ranking scale) and vitamin D levels. Authors highlighted that they included only surviving patients in the final analysis, so no data about vitamin D levels in dead patients were reported, not allowing a correct evaluation [14]. Moreover, a noteworthy aspect of this study [14] was that vitamin D level increased during the follow-up, whereas no supplementations were administered; authors properly suggested that secondary dietary changes could have contributed to these results which they did not evaluate. A special case is the association between vitamin D status and cognitive impairment in acute ischemic stroke patients. In fact, a recent study suggested the involvement of vitamin D deficiency in cognitive and mood disorders in the elderly [94], in quality of life in postmenopausal women [95], and in general anxiety disorders [96].