March 6, 2020

Study Shows Inflammation, Neuronal Damage and Transitory Disruption of the Blood Brain Barrier Following Single Generalized Convulsive Seizures

PURPOSE: Neuroinflammation and disruption of blood brain barrier (BBB) are important players in epileptogenesis, ictogenesis and pharmacoresistance. In this context, we investigated blood levels of HMGB1 and other inflammatory and BBB markers after generalized and focal to bilateral tonic-clonic seizures in serum, summarized under the term generalized convulsive seizures (GCS).

METHODS: The research team included consenting adults who were admitted to the epilepsy monitoring unit. Blood samples were drawn at baseline and immediately after a GCS as well as after 2, 6 and 24 h. The team measured leukocytes, c-reactive protein (CRP), the danger-associated molecular patterns (DAMPs) high mobility group box 1 (HMGB1) and S100, receptor of advanced glycation end products (RAGE) alongside the BBB markers intercellular adhesion molecule-1 (ICAM1) and matrix metalloproteinase 9 (MMP9). Noradrenaline and lactate measurements were available from a previous study. P-levels < 0.05 were regarded as significant.

RESULTS: Twenty-eight patients with 28 GCS were included. Leukocytosis occurred immediately after GCS and normalized within two hours (p < 0.001). S100 and HMGB1 both increased by ?80 % (p < 0.001). MMP9 peaked after six hours with levels at 48.6 % above baseline. RAGE decreased by 17.6 % with a nadir at 24 h. CRP increased by 118 % with a peak at 24 h. ICAM1 remained stable (p = 0.068). Postictal HMGB1 correlated with postictal leukocytosis (r = 0.42; p = 0.025) and with MMP9 levels six hours later (r = 0.374; p = 0.05). Postictal lactate levels correlated with MMP9 at 6 h (r = 0.48; p = 0.01) and CRP at 24 h (r = 0.39; p = 0.04). Postictal noradrenaline correlated with lactate (r = 0.57; p = 0.02) and leukocytes (r = 0.39; p = 0.047).

DISCUSSION: The serum level of the DAMPs HMGB1 and S100 increase immediately after GCS. The hypothetical mechanism includes central nervous processes, such as glutamate toxicity and ROS release from seizing neurons but also muscular tissues. BBB breakdown is marked by the release of MMP9. Further research is needed to understand the complex interactions between electrical and metabolic stress, neuroinflammation and BBB mechanics in seizures and epilepsy.

CONCLUSION: According to the researchers, this study reveals signs of inflammation, neuronal damage and transitory disruption of blood brain barrier following single generalized convulsive seizures, underscoring the widespread and possibly detrimental effects of recurrent seizures on brain properties. The long term impact on the disease course, however, is unclear.

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