Neurological presentations and therapeutic responses to cobalamin deficiency

Abstract

BackgroundThe clinical phenotypes of cobalamin (Cbl) deficiency is often overlooked in clinical practice as their presentations vary according to the level of involvement between the hematologic and nervous systems. Although the negative impact of Cbl deficiency on cognition has been underpinned, the reported therapeutic responses after Cbl supplement therapy differ. Therefore, we aimed to describe the neurological presentations of patients with Cbl deficiency and investigate the potential biomarkers in predicting therapeutic responses with emphasis on cognitive aspects. MethodsFifty consecutive neurologically symptomatic patients with Cbl deficiency (serum level ≤ 250 pg/ml) were recruited. Serological data, baseline Mini-Mental Status Examination (MMSE) and Cognitive Abilities Screening Instrument, initial white matter hyperintensities (WMHs), and follow-up cognitive evaluations after Cbl supplementation were analyzed. Comparisons between poor (ΔMMSE < 0) and good (ΔMMSE ≥ 0) responders were performed. ResultsThe most common neurological presentations included cognitive complaints (78%), dementia (38%), anxiety (38%), and cerebrovascular disease (28%). Among the patients with cerebrovascular disease, a high prevalence of recurrence (57.1%) and related major intracranial artery occlusion (35.7%) were noted. Of the 30 patients with follow-up cognitive evaluations, benefits on short-term memory and verbal fluency (both p < 0.05) were noted. Among the good responders, benefits in total MMSE and short-term memory scores were significant (both p < 0.05). The good responders had higher serum folate levels than the poor responders (p < 0.05; Cohen's d = 1.044). The poor responders had a greater total WMH load and deep white matter hyperintensities (DWMHs) [both p < 0.05; Hedges' g of total WMHs = 0.8429; Hedges' g of DWMHs = 0.8890]. ConclusionsAlthough Cbl supplement therapy had positive and domain-specific benefits on cognition, the therapeutic responses were modulated by serum folate levels and initial WMH load. A serum folate level between 16.8 and 24.6 ng/mL had a synergistic benefit on cognition during Neuropsychiatry (London) (2017) 7(3) 186Research Min-Chien Tu and 2.00 µmol/l had neurological improvements after Cbl therapy [11]. In addition, limited studies have stressed the importance of evaluating both cognition and structural brain imaging in patients with a low Cbl status [8,14]. Taken together, changes in cognition related to replacement therapy may be affected by preexisting and relevant brain parenchymal damage. Therefore, in this study we aimed to (i) describe the various neuropsychiatric presentations before and after Cbl supplement treatment, and (ii) elucidate factors predicting therapeutic responses among patients with Cbl deficiency. Materials and Methods Subjects and clinical registryThis study recruited 50 consecutive symptomatic patients with Cbl deficiency (≤ 250 pg/mL) [15], who visited the Department of Neurology of our hospital from March 2012 to March 2015. The initial neurological disease...