Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke

Merkler, Alexander E; Gialdini, Gino; Lerario, Michael P.; Parikh, Neal S; Morris, Nicholas; Kummer, Benjamin; Dunn, Lauren E; Reznik, Michael; Murthy, Santosh B.; Navi, Babak B.; Grinspan, Zachary M.; Iadecola, Costantino; Kamel, Hooman

doi:10.1161/strokeaha.117.020178

Cited by 48 publications

(35 citation statements)

References 28 publications

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“…Perhaps because of this, and other factors, there is considerable cellular injury (e.g., loss of dendrites [5]) and death in the perihematoma region [6]. Likely these ionic perturbations also directly impair neural function, and could lead to seizures, commonly seen in preclinical work and in patients [7,8]. Further indirect support comes from our research that shows that rehabilitation normalizes Cl levels in the peri-hematoma zone after experimental ICH [3], which might underlie how rehabilitation improves behavioral recovery.…”

Section: Introductionmentioning

confidence: 99%

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

et al. 2019

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The sulfonylurea 1 transient receptor potential melastatin 4 (Sur1-Trpm4) receptor is selectively expressed after intracerebral hemorrhage (ICH). This upregulation contributes to increases in intracellular sodium. Water follows sodium through aquaporin channels, leading to cytotoxic edema. Even after edema is thought to have resolved, ionic dyshomeostasis persists, as does blood-brain barrier (BBB) damage. Glibenclamide, a hypoglycemic agent that inhibits Sur1-Trpm4, has been shown to reduce BBB damage and edema following infusion of autologous blood into the brain (ICH) as well as after other brain injuries. In order to further assess efficacy, we used the collagenase ICH model in rats to test whether glibenclamide reduces edema, attenuates ion dyshomeostasis, improves BBB damage, and reduces lesion volume. We tested a widely-used glibenclamide dose shown effective in other studies (10 μg/kg loading dose followed by 200 ng/hr for up to 7 days). Early initiation of glibenclamide did not significantly impact edema (72 hours), BBB permeability (72 hours), or lesion volume after ICH (28 days). Recovery from neurological impairments was also not improved by glibenclamide. These results suggest that glibenclamide will not improve outcome in ICH. However, the treatment appeared to be safe as there was no effect on bleeding or other physiological variables.

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Section: Introductionmentioning

confidence: 99%

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

et al. 2019

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“…Additionally, ion dyshomeostasis is present for at least two weeks after collagenase ICH, giving a large therapeutic window in which bumetanide could theoretically provide benefit [2]. In patients, there is also a large therapeutic window in which electrical imbalances can be addressed, with post-ICH seizures occurring from onset until months after the stroke [27,28]. It should be noted that seizures were not observed in the whole blood model of ICH [16], but they do occur in the collagenase model [16,29].…”

Section: Introductionmentioning

confidence: 99%

Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat

et al. 2019

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After intracerebral hemorrhage (ICH), brain edema commonly occurs and can cause death. Along with edema, there are significant alterations in the concentrations of key ions such as sodium, potassium, and chloride, which are essential to brain function. NKCC1, a cation-chloride cotransporter, is upregulated after brain damage, such as traumatic injury and ischemic stroke. NKCC1 brings sodium and chloride into the cell, possibly worsening ion dyshomeostasis. Bumetanide, a specific NKCC1 antagonist, blocks the transport of chloride into cells, and thus should attenuate the increases in chloride, which should lessen brain edema and improve neuronal functioning post-ICH, as with other injuries. We used the collagenase model of ICH to test whether bumetanide treatment for three days (vs. vehicle) would improve outcome. We gave bumetanide beginning at two hours or seven days post-ICH and measured behavioural outcome, edema, and brain ion content after treatment. There was some evidence for a minor reduction in edema after early dosing, but this did not improve behaviour or lessen injury. Contrary to our hypothesis, bumetanide did not normalize ion concentrations after late dosing. Bumetanide did not improve behavioural outcome or affect lesion volume. After ICH, bumetanide is safe to use in rats but does not improve functional outcome in the majority of animals.

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“…In our study, late seizures were equally prevalent among the occipital and non‐occipital lobar ICH patients. The possible explanations are contradictory: the occipital ICH patients were younger but had smaller hematoma volume—the former associated with a higher and the latter with a lower risk of epilepsy 13,32,33 . The greater GW ratio in the occipital and temporal lobe 17 could be a predisposing factor for seizures.…”

Section: Discussionmentioning

confidence: 99%

“…The possible explanations are contradictory: the occipital ICH patients were younger but had smaller hematoma volume-the former associated with a higher and the latter with a lower risk of epilepsy. 13,32,33 The greater GW ratio in the occipital and temporal lobe 17 could be a predisposing factor for seizures. Furthermore, focal occipital seizures may sometimes remain unrecognized or be misdiagnosed as migraine.…”

Section: Why Is Occipital Location Associated With a Better Prognosis?mentioning

confidence: 99%

Occipital intracerebral hemorrhage—clinical characteristics, outcome, and post‐ICH epilepsy

et al. 2020

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The incidence of intracerebral hemorrhage (ICH) is approximately 25/100 000/y, 1 contributing to a cumulative lifetime risk of 8.2%. 2 Although the acute and 1-year mortality of ICH reaches 40% and 50%, respectively, 1,3 lobar location of bleeding seems to accompany a better prognosis. 4 Other factors associated with outcome include hematoma volume, severity, age, infratentorial origin, presence of intraventricular hemorrhage (IVH), and etiology. 5-8 In ischemic stroke, the location of the lesion impacts the severity, 9 outcome, 9 and risk of post-stroke epilepsy. 10 However, similar topological data on hemorrhage are scarce. In one study, isolated occipital hemorrhages were rare (4.6% of lobar ICH) and had better outcome than other lobar hemorrhages, 11 whereas another study did not find any occipital areas associating with lower acute mortality. 12 This retrospective observational registry-based study identifies occipital hemorrhages among consecutive spontaneous ICH patients treated in a single center. Our goal was to investigate the effect of

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Population-Based Assessment of the Long-Term Risk of Seizures in Survivors of Stroke

Abstract: Almost 10% of patients with stroke will develop seizures within a decade. Hemorrhagic stroke, nonwhite race, and younger age seem to confer the greatest risk of developing seizures.

Cited by 48 publications

References 28 publications

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

Glibenclamide, a Sur1-Trpm4 antagonist, does not improve outcome after collagenase-induced intracerebral hemorrhage

Failure of bumetanide to improve outcome after intracerebral hemorrhage in rat

Occipital intracerebral hemorrhage—clinical characteristics, outcome, and post‐ICH epilepsy

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