Data on the predictive factors for recurrent seizures in the elderly population are inconclusive or are not known for the majority of patients. This is especially true for the Egyptian population as no specific study was concluded to address this issue before to the best of our knowledge. This encouraged the design of this study in order to detect such factors and to correlate the results with various epidemiological, clinical, radiological, electrodiagnostic, and laboratory data.
In this study, the seizure frequency was significantly decreased after 6 months of follow-up. This may reflects the fact that epilepsy in elderly is not only easily controlled by AEDs  but also refers to the problem of poor adherence to the treatment by a large section of Egyptian elderly population either because of non-compliance or wrong prescription of AEDs or non-affordability with the medications price.
In this study, there was no significant relationship between gender, age, or age of onset and outcome. This is consistent with other studies as regard gender [9,10,11,12]. On the other hand, there was a report that hormone effect especially progesterone can account for difference in promoting and enhancing repair after traumatic brain injury and stroke which may enhance epilepsy outcome . Multivariate analyses of prognostic factors have found no independent correlation of age at onset with prognosis. It is likely that any differences are a reflection of the epilepsy syndromes that are prevalent among the various age groups . Analysis of the Glasgow cohort of newly diagnosed epilepsy suggested that outcomes were generally better in patients aged over 65 years at the onset of epilepsy . Possible explanations include lack the neuronal plasticity needed for the development of pharmacoresistance and reduced likelihood of genetic factors adversely affecting prognosis.
In this study, there was no significant relationship between family history of epilepsy and the outcome. Studies in children and adults have reported an association between family history of epilepsy and poorer prognosis . In generalized syndromes, this could be related to the underlying genetic mechanisms underpinning the epilepsy, which might also be responsible for determining drug response . The role of genetic factors in focal epilepsies is less clear. Genetically determined malformations of cortical development may play a role  as may pharmacogenetic traits that run in families . In this study, there was a statistically significant relationship between absence of medical comorbidities and good outcome of epilepsy but analysis of the relationship between specific illnesses such as hypertension, DM, ischemic heart disease, and outcome found no significant relationship. This may be due to the relative small number of cases with those illnesses. A study by Assis and colleagues also found association of a higher number of comorbidities with early seizure recurrence; thus, they hypothesized that patient multimorbidity is a risk factor for early seizure recurrence .
In this study, there was a significant relationship between post stroke epilepsy, either infarction or hemorrhage, and poor outcome. The presence of structural brain lesion was repeatedly reported as a risk factor for seizure recurrence in elderly [19,20,21,22,23]. The changed structure and function of the central nervous system (CNS) in symptomatic epilepsy led to hyper-excitability as the main cause of epilepsy . Brain lesions resulted in neuronal death and reactive gliosis. One of the mechanisms of drug-resistant epilepsy (DRE) is the “transporter hypothesis”, and the structural abnormalities damage the capillary endothelial cells that constitute the blood-brain barrier, leading to the over-expression of efflux transports and drug resistance .
In this study, history of status epilepticus was significantly associated with poor outcome of epilepsy. This was also reported in many studies [11, 19, 26]. Between 10 and 30% of people who have status epilepticus die within 30 days . The great majority of these people have an underlying brain condition causing their status seizure such as brain tumor, brain infection, brain trauma, or stroke. However, people with diagnosis of epilepsy who have a status epilepticus also have an increased risk of death if their condition is not stabilized quickly . In this study, there was no significant relationship between seizure precipitant and outcome. Some studies suggested that stress increases risk of seizure recurrence [29, 30].
In this study, no significant relationship was found between specific anti-epileptic medications used and the outcome. This is consistent with the previous studies which conclude that the majority of AEDs available have demonstrated a similar efficacy for treating epilepsy in elderly [31, 32]. Other studies found that lamotrigine was the most effective AED as measured by 12-month retention and seizure freedom, with levetiracetam a close second. Oxcarbazepine was consistently less effective than most other AEDs . In this study, there was a significant relationship between MRI findings and outcome, normal MRI brain was significantly associated with good outcome while both encephalomalacia and medial temporal pathology were significantly associated with poor outcome. This is consistent with the previous reports that presence of symptomatic etiology for epilepsy has a poor predictive value for seizure control; this is especially true for stroke in elderly as mentioned before. Analysis of 550 patients with localization-related epilepsy in Glasgow also reported worse remission rates in patient with hippocampal sclerosis than in focal epilepsies due to other causes .
In this study, there was a significant relationship between EEG finding (focal and generalized, slowing, or epileptiform discharge) and poor outcome. This is typically consistent with findings of Kim and colleagues in elderly population who stated that epileptiform activity on an EEG was a risk factor for recurrent seizure; this and non-specific abnormality on EEG were the main risk factors of recurrent seizure . On the other hand, study by Lindsten and colleagues have not found EEG to be independently predictive of outcome after adjusting for other factors. They concluded that the prognostic value of routine interictal EEG examination has not been established . In our opinion, an EEG performed soon after a seizure is more likely to detect such abnormalities and is likely to have greater prognostic value.
In this study, there was no significant relationship between laboratory abnormalities and outcome except for low serum Ca and low serum Mg which were associated with worse control of seizures. A study by Ushakiran and colleagues found definite association between serum calcium levels and the occurrence of febrile seizures in children. Although serum calcium levels were not in the hypocalcemic range, they were decreased enough to cause a statistical significance in precipitating febrile seizures . This finding was not studied in elderly before to best of our knowledge. Low serum Mg was also reported as a risk factor for febrile convulsions in children in a number of studies [37, 38] but also not studied in elderly population before.
Strengths of this study include being the first study to address the predictive factors of epilepsy outcome in elderly Egyptian population to the best of our knowledge, also; the prospective design of the study which allowed us to truly identify acute seizures as well as epileptic and non-epileptic events and to classify the seizure type and etiology according to the ILAE recommendations.
The study has some limitations which warrant mention. First, despite the size of the overall sample, there were small numbers in some subgroups as patients with certain illness in past medical history or patients on certain anti-epileptic drugs, which limited the statistical power for these analyses. Second, the study included elderly patients with seizures of any age of onset not just whom seizures started after age of 50; this group may have different outcome. Third, the relative short follow-up period (6 months) may not be enough to address the natural history of epilepsy in this population and longer periods of follow-up may be needed. There is a need for this study to be conducted with a larger number of participants and in multiple centers of epilepsy in Egypt, longer periods of follow-up may give a more accurate assessment of outcome of epilepsy in this population. A study including patients with seizure onset after age of 50 may be needed and results to be compared to those of this study. Also, there is a need for further studies investigating the role of low serum Ca and Mg in control of seizures in elderly population. Finally, there is a need for more studies assessing different aspects of epilepsy in elderly in Egyptian population.