Affiliations: Department of Neurology and Psychiatry, Assiut
University Hospital, Assiut, Egypt
Note: [] Address for correspondence: Sherifa Ahmed Hamed, MBBch., MSc.,
M.D., Consultant Neurologist, Associate Professor, Department of Neurology and
Psychiatry, Assiut University Hospital, P.O. Box 71516, Assiut, Egypt. Tel.: +2
088 2371820; Fax: +2 088 2333327; +2 088 2332278; E-mail:
hamed_sherifa@yahoo.com
Abstract: Cumulative evidences from experimental and clinical studies indicate
that in some patients, not only prolonged but also repetitive brief seizures,
may trigger series of damage promoting mechanisms which evolve over a period of
time (up to years). They result in progressive degeneration and loss of
function of several neuronal cell populations, thus rending the brain abnormal
and resistant to antiepileptic medications (AEDs). This probably explains that
in some patients, a) there is a delay from the onset of brain insult to the
seizure onset, and b) suppression of seizures by AEDs is alone
insufficient without clear prediction of disease progression. In this review,
the analysis of information follows the assumption that epilepsy is a slowly
progressive and a neurobiologically pleotropic disorder. Interaction between
genes, neurotransmitters, ion channels, acid-base balance, mitochondria,
calcium, glutamate and oxidative/antioxidants mechanisms, will determine the
fate of the epilepsy process. The concept of neuroprotection aims not only to
suppress seizures (anticonvulsant effect), but also to strengthen the
auto-protective and repair mechanisms (antiepileptogenic and
disease-modification effects) which prevent the development of spontaneous
seizures, cognitive and behavioral problems later in life. This review is
focusing on molecular evaluation of several models of epilepsy for the
potential to follow disease modification and neuroprotection. Although AEDs of
today possess multiple mechanisms of action, but mostly they are treating one
part of the disease which is the seizures and do not offer high prospects of
modification of the disease. This review is also discussing the prospects of
novel drugs, molecular manipulations and cell therapy which address disease
modification as approachs that will dominate the field of drug development and
research on epilepsy in the future.
