Intravenous immunoglobulins in refractory childhood-onset epilepsy: effects on seizure frequency, EEG activity, and cerebrospinal fluid cytokine profile.
OBJECTIVE
Several studies have reported favorable effects of intravenous immunoglobulins (IVIG) in refractory epilepsy. Evidence substantiating an immunomodulatory action is scarce. In an open-label study, we prospectively investigated the effect of IVIG on clinical, EEG and serum/CSF immunological parameters in patients with refractory childhood-onset epilepsy.


METHODS
Thirteen patients (median age 6.9 years; range 1.6-25.8) with refractory seizures despite 3-4 antiepileptic drug regimens were given IVIG (Sandoglobulin, ZLB-Behring, add-on, 4 x 400 mg/kg/3 weeks). Seizure frequency, 24-h video-EEG, and CSF/serum immunological parameters and cytokine profiles (IL-6/IL-8/IL-12/IL-10) were documented before and after completion of the course.


RESULTS
Seizure frequency was reduced by > or = 50% in four, and by 25%-50% in three patients. In contrast, variation in automatically recorded spike counts (1-h-wake and -sleep) did not correlate with clinical improvement. Serum immunological parameters showed variable deviations in eight patients (e.g., IgG(2) deficiency) and CSF immunoblotting showed oligoclonal bands in two patients. Blood-brain barrier permeability was normal in 12 patients. IL-6 and IL-8 were clearly detectable in CSF of all patients; the levels were significantly higher than those in plasma but remained unaffected by IVIG treatment.


CONCLUSIONS
Despite unchanged EEG spike counts, substantial reductions in seizure frequency occurred in 7 of 13 patients, suggesting that IVIG hinder progression of central epileptic activity into clinical seizures. Intrathecal presence of IL-8 and IL-6 was documented in all patients, but was unaffected by IVIG, suggesting that their production is directly related to electrical seizure activity and that IVIG may act through interference with immune pathways downstream to IL-6 and IL-8.
Billiau
An D
AD
Laboratory of Experimental Transplantation, University of Leuven, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumLab of Experimental Immunology, KULeuven, Leuven, Belgium.
Witters
Peter
P
Laboratory of Experimental Transplantation, University of Leuven, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumLab of Experimental Immunology, KULeuven, Leuven, Belgium.
Ceulemans
Berten
B
Laboratory of Experimental Transplantation, University of Leuven, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumLab of Experimental Immunology, KULeuven, Leuven, Belgium.
Kasran
Ahmad
A
Laboratory of Experimental Transplantation, University of Leuven, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumLab of Experimental Immunology, KULeuven, Leuven, Belgium.
Wouters
Carine
C
Laboratory of Experimental Transplantation, University of Leuven, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumLab of Experimental Immunology, KULeuven, Leuven, Belgium.
Lagae
Lieven
L
Laboratory of Experimental Transplantation, University of Leuven, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumPediatric Rheumatology, University Hospital Gasthuisberg, Leuven, BelgiumLab of Experimental Immunology, KULeuven, Leuven, Belgium.
D000293:Adolescent; D017668:Age of Onset; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm / Q000502:physiology; D016207:Cytokines / Q000097:blood / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D004569:Electroencephalography / Q000187:drug effects / Q000706:statistics & numerical data*; D004827:Epilepsy / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007223:Infant; D015850:Interleukin-6 / Q000097:blood / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D011446:Prospective Studies; D016896:Treatment Outcome; D014743:Videotape Recording
D000927:Anticonvulsants; D016207:Cytokines; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D015850:Interleukin-6; D016209:Interleukin-8