Objective: The assay of serum cobalamin (Cbl) level is commonly used to diagnose Cbl deficiency. Unexpectedly, the elevated Cbl levels may be determined in some of the patients and its interpretation is difficult. We investigated the association between elevated Cbl levels and a variety of clinical entities in patients presenting with various neurological symptoms.
Methods: The data were obtained from the patients' electronic medical records in a tertiary hospital affiliated with a university. The pediatric patients with serum Cbl levels above 1000 pg/mL were included in the study. The patients with serum Cbl levels below 900 pg/mL and above 200 pg/mL constituted the control group.
Results: The mean Cbl level of the patients with neurological problems was 1424.2±354.2 pg/mL, whereas the average Cbl level of neurologically healthy was 1316±317.8 pg/mL, and the difference was statistically significant. While the rate of having neurological deficits or symptoms in the study group was found to be 24%, this rate was only 18% in the control group. Unexpectedly, despite elevated Cbl level, the high mean corpuscular volume rate was higher in the study group compared to the control group.
Conclusion: This study highlights the importance of the disorders of Cbl metabolism in patients presenting with various neurological symptoms. In children with neurological deficits, serum Cbl levels should be checked. In case of high Cbl level is determined, patients should be followed up closely, and further investigations should be performed in terms of Cbl metabolism disorders.
Cartwheel interneurons of the dorsal cochlear nucleus (DCN) potently suppress multisensory signals that converge with primary auditory afferent input, and thus regulate auditory processing. Noradrenergic fibers from locus coeruleus project to the DCN, and α2-adrenergic receptors inhibit spontaneous spike activity but simultaneously enhance synaptic strength in cartwheel cells, a dual effect leading to enhanced signal-to-noise for inhibition. However, the ionic mechanism of this striking modulation is unknown. We generated a glycinergic neuron-specific knockout of the Na+ leak channel NALCN, and found that its presence was required for spontaneous firing in cartwheel cells. Activation of α2-adrenergic receptors inhibited both NALCN and spike generation, and this modulation was absent in the NALCN knockout. Moreover, α2-dependent enhancement of synaptic strength was also absent in the knockout. GABAB receptors mediated inhibition through NALCN as well, acting on the same population of channels as α2 receptors, suggesting close apposition of both receptor subtypes with NALCN. Thus, multiple neuromodulatory systems determine the impact of synaptic inhibition by suppressing the excitatory leak channel, NALCN.