426
Biomarkers of Epilepsy
With so many different types of seizures and causes of epilepsy, there are no univer-
sal biomarkers except EEG measurements. Some biomarkers detect diseases that
manifest in seizures. There are no characteristic biomarkers of idiopathic epilepsy
except those for monitoring seizures and response to treatment. Development of
reliable epilepsy biomarkers would be a major advance in personalized manage-
ment of epilepsy. A classifi cation of biomarkers of epilepsy is shown in Table 12.4.
Genetics of epilepsy is discussed briefl y in the following section. Biochemical
biomarkers of apoptosis, both the proapoptotic Fas and the anti-apoptotic Bcl-2, are
proportionately elevated in sera of patients with idiopathic epilepsy, and their levels
are related to the seizure severity and frequency. Pyridoxine defi ciency is an uncom-
mon but important cause of intractable seizures presenting in infancy and early
childhood. It is usually treated by pyridoxine supplementation. Some children with
intractable seizures respond to pyridoxal phosphate rather than pyridoxine, includ-
ing a rare form of neonatal epileptic encephalopathy shown to be due to mutations
in the PNPO gene for pyridox(am)ine 5’-phosphate oxidase. Although the biochem-
ical explanation for this fi nding is not clear, elevated pipecolic acid levels may serve
as a diagnostic biomarker for patients with pyridoxine-dependent seizures. Levels
of both pipecolic acid and certain metabolites shown to be elevated in patients with
PNPO mutations should be measured, and therapeutic trials of pyridoxal phosphate
as well as pyridoxine should be considered early in the course of the management
of infants and young children with intractable seizures.
Results of a clinical study show that serum HSP70 levels have an inverse correla-
tion with hippocampal volume after controlling for the effect of age in patients with
temporal lobe epilepsy (TLE), and HSP70 is a biomarker for prediction of higher
frequencies of seizures in these patients (Chang et al. 2012 ). HSP70 is considered to
Table 12.4 Biomarkers of epilepsy
Gene mutations in genetic epilepsies
EEG patterns
MRI biomarkers
Protein biomarkers
Protein high-mobility group box 1 (HMGB1)
Biochemical markers in blood
Serum prolactin
Fas and bcl-2
Biomarkers in cerebrospinal fl uid
Lactate elevation following seizures
Metabolites in inborn errors of metabolism with infantile epilepsy
Neuron-specifi c enolase (biomarker for neuronal injury)
Cytkines following seizures
S100 protein
© Jain PharmaBiotech12 Personalized Management of Neurological Disorders