This study aimed to evaluate ghrelin effect in adult epileptic patients and in response to AEDs. We found that serum acylated ghrelin (AG), unacylated ghrelin (UAG), and urine ghrelin (AG) levels in epileptic patients were statistically higher than controls, those of the similar age, sex, and BMI. This was in accordance of Berilgent and colleagues study [12] who stated higher levels of serum ghrelin regardless type of epilepsy. Others found a significant increase of serum, urine, and saliva levels of AG and UAG in epileptic children [13]. Additionally, the investigators established that enhancement of ghrelin in epilepsy might stimulate the slow-way sleep and prolong non-rapid eye movements (non REM) sleep during the night, in which the seizures have a tendency to occur [12].
Others stated different results as Varrasi and colleagues [14] as they found inter-ictal AG and UAG levels in adult epileptic patients with various epilepsy forms were not altered from those healthy controls.
Conversely, others found a reduction of serum ghrelin levels in epileptic patients before treatment than in controls. They found a reduction in plasma levels of this peptide almost coincident with convulsions [5]. Other studies were done on rates settled a significant decreased of serum acylated ghrelin level post-ictal that could be attributed to its uptake by brain to represent an antiepileptic effect. But reduction of unacylated ghrelin and total ghrelin level failed to range statistical significance [15]. Aydin and colleagues [5] were attributed that AG uptake was increased by CNS structures to modify epileptic discharges so its serum level decrease which was more evident specifically after seizure stimulation. The second clarification is due to diminution of ghrelin to prevent the production of free radicals during seizures.
This contrasting finding could be based on heterogeneous patient features and antiepileptic treatment, different epilepsy phases, or measurement techniques. Contradictory finding that was also obtained in pediatric populations may be attributed to the presence of other additional confounding factors such as the modulation of ghrelin secretion by pubertal stage, age, weight gain, and drug effects [7].
This study showed positive correlations between serums AG, UAG, and urine AG levels and duration of epilepsy. This was stated by Varrasi and colleagues [14] who reported that AG and UAG levels were in direct proportion of epilepsy duration regardless of seizure type, AEDs response, or number of AEDs, which may denote a long-term compensatory mechanism, opposed to the epileptic process. In addition to that, multivariate logistic regression analysis of high laboratory parameters concluded that high AG and UAG levels were significantly associated with prolonged epilepsy duration and AEDs-responsive patients.
This finding was in agreement with others who found higher serum AG and UAG levels in responders to AEDs compared with controls and non-responders and these changes occurred in a way independently on type of AEDs [16]. Also, AG and UAG were downregulated in children affected by refractory epilepsy [17]. That gives the potential role played by these neuropeptides as anticonvulsants; such properties could be linked to epileptic patients and especially intractable seizures [18].
Ge and colleagues [18] supposed the possible mechanisms of ghrelin’s anticonvulsant properties in the subsequent three features: firstly, Ghrelin can reduce cognitive dysfunction in epileptogenesis by endorsing hippocampal synaptic plasticity. Secondly, ghrelin applies anticonvulsant effectiveness via thought-provoking secretion of neuropeptide Y (NPY) which is one of the most studied neuropeptides in epilepsy. NPY is richly expressed in GABAergic interneurons of the central nervous system including the hippocampus. Thirdly, ghrelin exerts neuro-protective and anti-inflammatory belongings and protect neuron from epilepsy-induced neuronal damage.
