Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction
Abstract
:1. Introduction
2. Results
3. Discussion
3.1. MMP-9
3.2. MMP-2
3.3. CCL-2
3.4. Other Molecules
3.5. Co-Variables
3.6. Strengths and Limitations
4. Materials and Methods
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Mean ± SEM | Median | Min–Max | |
---|---|---|---|
age (years) | 44.84 ± 2.26 | 42 | 19–82 |
age at epilepsy onset (years) | 24.45 ± 2.35 | 21 | 1–67 |
epilepsy duration (years) | 20.43 ± 1.90 | 17 | 2–57 |
time since last seizure (days) | 607.60 ± 114.30 | 305 | 7–4036 |
positive family history of epilepsy (number of patients) | 7 | ||
positive history of febrile seizures (number of patients) | 3 | ||
drug-resistance (number of patients) | 25 |
EPILEPSY ETIOLOGY | |
---|---|
GENETIC EPILEPSY | 18 |
idiopathic generalized epilepsy | 18 |
STRUCTURAL-METABOLIC EPILEPSY | 24 |
MTLE * with hippocampal sclerosis | 2 |
MTLE without hippocampal sclerosis | 5 |
post-traumatic epilepsy | 6 |
vascular epilepsy | 5 |
epilepsy due to neonatal hypoxic-ischemic encephalopathy | 2 |
epilepsy due to congenital malformations of the CNS | 2 |
post-infectious epilepsy | 2 |
EPILEPSY OF UNKNOWN ETIOLOGY | 7 |
Seizure Type | ||
---|---|---|
Both Primary and Secondary Tonic-Clonic Seizures | Focal Seizures (Motor and Non-Motor) | Both Focal Seizures Secondary Generalized Tonic-Clonic Seizures |
21 | 7 | 21 |
Seizure Count at Baseline (T0) | |||||||||
---|---|---|---|---|---|---|---|---|---|
History | T0-T1 | ||||||||
Period [m–months. d–days] | 12 m | 6 m | 3 m | 1 m | 7 d | 1 m | 3 m | 6 m | 12 m |
mean ± SEM | 6.18 ± 1.56 | 4.12 ± 1.13 | 1.65 ± 0.44 | 0.87 ± 0.12 | 0.08 ± 0.28 | 0.61 ± 0.28 | 2.36 ± 1.10 | 4.47 ± 1.78 | 6.49 ± 2.52 |
median | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
min–max | 0–57 | 0–44 | 0–14 | 0–3 | 0–1 | 0–13 | 0–51 | 0–74 | 0–109 |
Seizure Count at Follow-Up (T1) | |||||||||
---|---|---|---|---|---|---|---|---|---|
T0-T1 | T1-T2 | ||||||||
Period [m–months. d–days] | 12 m | 6 m | 3 m | 1 m | 7 d | 1 m | 3 m | 6 m | 12 m |
mean ± SEM | 7.31 ± 2.54 | 3.71 ± 1.28 | 2.06 ± 0.66 | 0.57 ± 0.19 | 0.06 ± 0.05 | 0.61 ± 0.20 | 1.61 ± 0.52 | 3.16 ± 1.02 | 6.88 ± 2.10 |
median | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
min–max | 0–108 | 0–54 | 0–25 | 0–7 | 0–2 | 0–7 | 0–21 | 0–42 | 0–75 |
True | False | |
---|---|---|
normal EEG | 18 | 31 |
abnormal background activity | 7 | 42 |
focal slow waves | 26 | 23 |
epileptiform discharges | 9 | 40 |
Feature | 2-Year Seizure Recurrence Risk | 5-Year Seizure Recurrence Risk | 10-Year Chance of Seizure-Freedom (Seizure-Free for at Least 1 Year) |
---|---|---|---|
mean ± SEM (%) | 77.76 ± 1.48 | 85.60 ± 1.10 | 25.12 ± 1.86 |
median (%) | 78 | 89 | 27 |
min–max (%) | 43–90 | 53–90 | 20–60 |
Number of Patients | |||
---|---|---|---|
Monotherapy at T0/T1 | Polytherapy at T0/T1 | Total at T0/T1 | |
valproate | 16/14 | 9/10 | 25/24 |
carbamazepine | 7/7 | 5/4 | 12/11 |
lamotrigine | 6/6 | 5/6 | 11/12 |
levetiracetam | 4/5 | 5/6 | 9/11 |
topiramate | 0/0 | 3/3 | 3/3 |
gabapentin | 0/0 | 2/2 | 2/2 |
phenobarbital | 1/1 | 0/0 | 1/1 |
phenytoin | 0/0 | 1/1 | 1/1 |
total | 34/32 | 15/17 | 49 |
Baseline | Follow-Up | ||||||
---|---|---|---|---|---|---|---|
Mean ± SEM | Median | Min–Max | Mean ± SEM | Median | Min–Max | p | |
MMP-9 [ng/mL] | 780.33 ± 72.39 | 601.92 | 125.22 –2555.34 | 449.79 ± 48.51 | 416.44 | 10.15–1699.80 | <0.0001 |
TIMP-1 [ng/mL] | 236.83 ± 16.38 | 259.14 | 2.69–464.72 | 100.60 ± 7.71 | 100.85 | 3.83–216.35 | <0.0001 |
MMP-2 [ng/mL] | 289.80 ± 15.35 | 272.59 | 133.86–548.59 | 200.84 ± 13.62 | 211.34 | 41.32–496.85 | <0.0001 |
CCL-2 [pg/mL] | 325.95 ± 21.12 | 312.35 | 112.47–771.43 | 434.65 ± 27.60 | 394.29 | 93.14–1299.29 | <0.0001 |
P-sel [ng/mL] | 105.48 ± 9.70 | 91.09 | 6.62 –240.68 | 159.10 ± 15.65 | 135.79 | 16.47–389.76 | 0.0035 |
MMP-2/TIMP-2 | 1.95 ± 0.10 | 1.84 | 0.83 –3.86 | 1.28 ± 0.08 | 1.33 | 0.29 –3.41 | <0.0001 |
TIMP-2 [ng/mL] | 149.71 ± 4.45 | 146.91 | 95.16 –257.58 | 159.51 ± 4.57 | 164.07 | 92.84–244.59 | 0.094 |
S100B [pg/mL] | 43.32 ± 12.32 | 24.93 | 0.29 –571.13 | 42.34 ± 13.2 | 11.88 | 0.5 –516.25 | 0.2674 |
ICAM-1 [ng/mL] | 181.91 ± 9.75 | 163.02 | 103.34 –437.03 | 167.02 ± 8.4 | 155.19 | 36.03–369.73 | 0.06 |
TSP-2 [ng/mL] | 29.13 ± 2.42 | 25.55 | 5.71 –68.80 | 26.35 ± 1.8 | 22.44 | 11.22 –66.6 | 0.4062 |
MMP-9/TIMP-1 | 7.79 ± 2.58 | 2.77 | 0.66 –131.21 | 14.39 ± 4.24 | 6.21 | 0.07–299.90 | 0.1645 |
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Bronisz, E.; Cudna, A.; Wierzbicka, A.; Kurkowska-Jastrzębska, I. Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction. Int. J. Mol. Sci. 2022, 23, 14712. https://doi.org/10.3390/ijms232314712
Bronisz E, Cudna A, Wierzbicka A, Kurkowska-Jastrzębska I. Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction. International Journal of Molecular Sciences. 2022; 23(23):14712. https://doi.org/10.3390/ijms232314712
Chicago/Turabian StyleBronisz, Elżbieta, Agnieszka Cudna, Aleksandra Wierzbicka, and Iwona Kurkowska-Jastrzębska. 2022. "Serum Proteins Associated with Blood–Brain Barrier as Potential Biomarkers for Seizure Prediction" International Journal of Molecular Sciences 23, no. 23: 14712. https://doi.org/10.3390/ijms232314712