Der Einfluss von Calcium auf die corticale Exzitabilität - Eine explorative TMS Studie

A very rare complication of hypo- and hypercalcaemia are seizures. The pathomechanism behind these seizures is still not fully understood. Therefore we studied the influence of the calcium blood level on the cortical excitability in 15 Patients (8w, 7m, 54, 2+14, 8 years) with primary hyperparathyroidism before and after parathyroidectomy. To measure the cortical excitability we used single and paired-pulse transcranial magnetic stimulation (TMS). We assessed the resting motor threshold (RMT, the cortical silent period (CSP), the intracortical inhibition (ICI), the intracortical facilitation (ICF) and the late intracortical inhibition (LICI) before and after parathyroidectomy. The calcium and parathormone blood levels were also measured before and after the operation. In 10 patients we performed the TMS within 4 days postoperative and in 5 patients with at least 30 days distance to the operation. To be able to differentiate between central and peripheral effects of the calcium blood level we also checked the nerve conduction velocity (NCV), the f-waves and the grip force. To evaluate the symptoms of pHPT we used the questionnaires BDI II, SF-36 and the PAS score. To our knowledge this is the first study using a German version of the PAS score. Following studies performed in the English speaking world (Great Britain, Canada and Australia) the PAS score is considered to be the best tool to determine the unspecific symptoms of pHPT. We found a non-significant reduction of the cortical excitability in the group measured early after the operation. There was a rise of the RMT and a prolongation of the CSP in comparison to the preoperative measurement. The opposite effect was seen in the group examined > 30 days after the operation. The RMT was higher post- than preoperative. Therefore the cortical excitability rose postoperatively. All the other TMS parameters remained unchanged. We also couldn’t detect a difference between the pre- and postoperative nerve conduction velocity, the f-waves and the grip force. Therefore, it seems unlikely that changes in the peripheral nervous system are responsible for the changes we detected in the TMS parameters as compared to postoperatively. As we observed opposite effects in the groups measured early vs. late postoperatively we hypothesize that different mechanism underlie the detected changes. The reduction of the cortical excitability directly postoperatively could be due to an augmentation of the cortical inhibition through serotonin and dopamine. The intensification of the inhibition could be a consequence of the decrease of the calcium blood level. This seems possible because hypercalcaemia is thought to cause a deficiency of serotonin and dopamine. The augmentation of the cortical excitability in the group measured > 30 days postoperatively is likely to be caused directly through the decline of the calcium blood level postoperatively. It is known that calcium stabilizes excitable membranes. Therefore the question comes up, whether a reduction of calcium lessening the stabilization of excitable membranes would correspondingly raise the cortical excitability? To further investigate the hypotheses we developed from this explorative study it seems necessary to study the effect of dopamine and serotonin on the cortical excitability in vitro and in vivo. Another field that needs additional examination is the connection between calcium and the monoamines dopamine and serotonin. All used questionnaires found an improvement of health in the participants. Moreover the results are in accordance to previously published studies on patients with pHPT and these questionnaires. This is especially of interest for the PAS-Score, because it shows that our translation did not negatively affect the usefulness of the PAS-Score in detecting changes in health and wellbeing in this population. To further validate the German version of the PAS score it is necessary to perform a follow-up study with a larger study size. We couldn’t find a correlation between the used questionnaires and the TMS parameters. It remains unknown if we simply couldn’t detect a relationship because of our small study size or if there really is no correlation. This also needs further investigation.