mRNA profiling of caspase-3 and neurofilament light chain in Lennox-Gastaut Syndrome
Sandeep Kumar Gupta1, Firoz M Nizami1, Ashish Kant Dubey1
1Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014, India.
Purpose:
Lennox-Gastaut Syndrome (LGS) is characterized by multiple refractory seizures. Higher seizure burden in LGS may be associated with higher expression of neurofilament light chain (NfL) and caspase-3, but such studies are very few. We report mRNA profiling of NfL and caspase-3 in LGS and their association with seizure burden, MRI abnormalities, and electroencephalography (EEG) findings.
Methods:
Twenty-three LGS patients and 14 healthy matched controls were recruited from a tertiary care teaching hospital. The diagnosis of LGS was based on seizure onset before 8 years of age, multiple refractory seizure types, cognitive impairment, and slow spike wave (SSW) and/or generalized paroxysmal fast activity (GPFA) in EEG. Their clinical details, MRI abnormalities, and burden of SSW and GPFA were recorded. The mRNA profiling of NfL and caspase-3 was done using real-time polymerase chain reaction (real-time PCR) from whole blood.
Results:
The patients had higher expression of NfL [5.36 (Q1, 2.26-Q1, 11.74) vs 0.89 (Q1, 0.55-Q3, 2.19); P = 0·004] and caspase-3 [2.56 (Q, 1.02-Q3, 4.58) vs 0.87 (Q1, 0.52-Q3, 2.93); P = 0·02] compared to the controls. NfL fold changes positively correlated with monthly burden of focal seizures (r = 0.52) and caspase-3 (r = 0.41). Caspase-3-fold changes had a positive correlation with the monthly burden of total seizures (r = 0.53), atypical absence seizures (r = 0.81), and myoclonic seizures (r = 0.50).
Conclusion:
The higher expression of NfL and caspase-3 in LGS, and their association with seizure burden, suggests seizure-induced neuroaxonal injury and apoptosis. These biomarkers may be used to monitor the therapeutic effect.
