Lacosamide in patients with epilepsy of cerebrovascular etiology

Rosenow, Felix; Brandt, Christian; Bozorg, Ali; Dimova, Svetlana; Steiniger‐Brach, Björn; Zhang, Ying; Ferro, B; Holmes, Gregory L.; Kälviäinen, Reetta

doi:10.1111/ane.13230

Cited by 17 publications

(8 citation statements)

References 20 publications

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“…LCM is generally well-tolerated and effective in patients with epilepsy of cerebrovascular etiology [ 33 ] and intravenously administered LCM showed high efficacy and tolerability in non-convulsive SE (NCSE) following stroke in patients older than 70 years [ 34 ].…”

Section: Current Indications and Drug Treatment Optionsmentioning

confidence: 99%

“…Data for monotherapies suggested both a better antiseizure efficacy and favourable pharmacokinetic profile (i.e. fewer interactions and less negative influence on lipid concentrations) for LCM in comparison to CBZ [ 33 ]. Publications on the clinical effectiveness and tolerability of ASM for PSE treatment are summarised in Table 1 .…”

Section: Current Indications and Drug Treatment Optionsmentioning

confidence: 99%

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Seizures and epilepsy in patients with ischaemic stroke

Zöllner

Schmitt

Rosenow

et al. 2021

Neurol. Res. Pract.

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Background With the increased efficacy of stroke treatments, diagnosis and specific treatment needs of patients with post-stroke seizures (PSS) and post-stroke epilepsy have become increasingly important. PSS can complicate the diagnosis of a stroke and the treatment of stroke patients, and can worsen post-stroke morbidity. This narrative review considers current treatment guidelines, the specifics of antiseizure treatment in stroke patients as well as the state-of-the-art in clinical and imaging research of post-stroke epilepsy. Treatment of PSS needs to consider indications for antiseizure medication treatment as well as individual clinical and social factors. Furthermore, potential interactions between stroke and antiseizure treatments must be carefully considered. The relationship between acute recanalizing stroke therapy (intravenous thrombolysis and mechanical thrombectomy) and the emergence of PSS is currently the subject of an intensive discussion. In the subacute and chronic post-stroke phases, important specific interactions between necessary antiseizure and stroke treatments (anticoagulation, cardiac medication) need to be considered. Among all forms of prevention, primary prevention is currently the most intensively researched. This includes specifically the repurposing of drugs that were not originally developed for antiseizure properties, such as statins. PSS are presently the subject of extensive basic clinical research. Of specific interest are the role of post-stroke excitotoxicity and blood–brain barrier disruption for the emergence of PSS in the acute symptomatic as well as late (> 1 week after the stroke) periods. Current magnetic resonance imaging research focussing on glutamate excitotoxicity as well as diffusion-based estimation of blood–brain barrier integrity aim to elucidate the pathophysiology of seizures after stroke and the principles of epileptogenesis in structural epilepsy in general. These approaches may also reveal new imaging-based biomarkers for prediction of PSS and post-stroke epilepsy. Conclusion PSS require the performance of individual risk assessments, accounting for the potential effectiveness and side effects of antiseizure therapy. The use of intravenous thrombolysis and mechanical thrombectomy is not associated with an increased risk of PSS. Advances in stroke imaging may reveal biomarkers for PSS.

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Section: Current Indications and Drug Treatment Optionsmentioning

confidence: 99%

Section: Current Indications and Drug Treatment Optionsmentioning

confidence: 99%

Seizures and epilepsy in patients with ischaemic stroke

Zöllner

Schmitt

Rosenow

et al. 2021

Neurol. Res. Pract.

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“…The extent to which the unwanted reactions linked to the LCS treatment was explained by its on the magnitude, gating, and V hys of I K(A) and thus warrants further investigation. Findings from the present study tend to be informative as they highlight the proof-of-concept that needs to be taken into consideration since the wide spectrum of LCS's beneficial effects has been clinically observed [1][2][3][4][5][6][7][9][10][11][12][13][14][15][16][17][18][19][20][21]24,25,32].…”

Section: Discussionmentioning

confidence: 97%

“…Lacosamide (LCS, Vimpat ® ) is regarded as a functionalized amino acid (available orally and intravenously) for the treatment of a wide variety of seizures, such as focal-onset seizure or refractory status epilepticus [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. However, of note, although LCS is safe and effective in anti-convulsant activities, the unwanted events following LCS treatment, such as dizziness, abnormal vision, diplopia, ataxia, personality changes, and cardiovascular adverse events (e.g., sinus node dysfunction), have gradually emerged [3,6,7,[18][19][20][21][22][23][24]. The risk of myoclonic seizure was also reported to occur during the treatment with this drug [25].…”

Section: Introductionmentioning

confidence: 99%

Evidence for Inhibitory Perturbations on the Amplitude, Gating, and Hysteresis of A-Type Potassium Current, Produced by Lacosamide, a Functionalized Amino Acid with Anticonvulsant Properties

Cho

Chuang

2022

IJMS

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Lacosamide (Vimpat®, LCS) is widely known as a functionalized amino acid with promising anti-convulsant properties; however, adverse events during its use have gradually appeared. Despite its inhibitory effect on voltage-gated Na+ current (INa), the modifications on varying types of ionic currents caused by this drug remain largely unexplored. In pituitary tumor (GH3) cells, we found that the presence of LCS concentration-dependently decreased the amplitude of A-type K+ current (IK(A)) elicited in response to membrane depolarization. The IK(A) amplitude in these cells was sensitive to attenuation by the application of 4-aminopyridine, 4-aminopyridine-3-methanol, or capsaicin but not by that of tetraethylammonium chloride. The effective IC50 value required for its reduction in peak or sustained IK(A) was calculated to be 102 or 42 µM, respectively, while the value of the dissociation constant (KD) estimated from the slow component in IK(A) inactivation at varying LCS concentrations was 52 µM. By use of two-step voltage protocol, the presence of this drug resulted in a rightward shift in the steady-state inactivation curve of IK(A) as well as in a slowing in the recovery time course of the current block; however, no change in the gating charge of the inactivation curve was detected in its presence. Moreover, the LCS addition led to an attenuation in the degree of voltage-dependent hysteresis for IK(A) elicitation by long-duration triangular ramp voltage commands. Likewise, the IK(A) identified in mouse mHippoE-14 neurons was also sensitive to block by LCS, coincident with an elevation in the current inactivation rate. Collectively, apart from its canonical action on INa inhibition, LCS was effective at altering the amplitude, gating, and hysteresis of IK(A) in excitable cells. The modulatory actions on IK(A), caused by LCS, could interfere with the functional activities of electrically excitable cells (e.g., pituitary tumor cells or hippocampal neurons).

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“…The rate of switch to LCM should be interpreted in the light of late marketing in Italy, which approved LCM monotherapy only in very late 2018. Therefore, switch rates might have been underestimated, with a substantial proportion of people with PSE expected to have a first or second prescription of LCM in more recent times, according to the favorable efficacy and tolerability profile ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Incidence and Antiseizure Medications of Post-stroke Epilepsy in Umbria: A Population-Based Study Using Healthcare Administrative Databases

Costa

Cesarini

Franchini³

et al. 2022

Front. Neurol.

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Introduction: Post-stroke epilepsy (PSE) requires long-term treatment with antiseizure medications (ASMs). However, epidemiology of PSE and long-term compliance with ASM in this population are still unclear. Here we report, through population-level healthcare administrative data, incidence, risk factors, ASM choice, and ASM switch over long-term follow-up.Materials and Methods: This is a population-based retrospective study using Umbria healthcare administrative database. Population consisted of all patients with acute stroke, either ischaemic or hemorrhagic, between 2013 and 2018. ICD-9-CM codes were implemented to identify people with stroke, while PSE was adjudicated according to previously validated algorithm, such as EEG and ≥1 ASM 7 days after stroke.Results: Overall, among 11,093 incident cases of acute stroke (75.9% ischemic), 275 subjects presented PSE, for a cumulative incidence of 2.5%. Patients with PSE were younger (64 vs. 76 years), more frequently presented with hemorrhagic stroke, and had longer hospital stay (15.5 vs. 11.2 days) compared with patients without PSE. Multivariable Cox proportional hazards models confirmed that PSE associated with hemorrhagic stroke, younger age, and longer duration of hospital stay. Levetiracetam was the most prescribed ASM (55.3%), followed by valproate and oxcarbazepine. Almost 30% of patients prescribed with these ASMs switched treatment during follow-up, mostly toward non-enzyme-inducing ASMs. About 12% of patients was prescribed ASM polytherapy over follow-up.Conclusions: Post-stroke epilepsy is associated with hemorrhagic stroke, younger age, and longer hospital stay. First ASM is switched every one in three patients, suggesting the need for treatment tailoring in line with secondary prevention.

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Lacosamide in patients with epilepsy of cerebrovascular etiology

Cited by 17 publications

References 20 publications

Seizures and epilepsy in patients with ischaemic stroke

Seizures and epilepsy in patients with ischaemic stroke

Evidence for Inhibitory Perturbations on the Amplitude, Gating, and Hysteresis of A-Type Potassium Current, Produced by Lacosamide, a Functionalized Amino Acid with Anticonvulsant Properties

Incidence and Antiseizure Medications of Post-stroke Epilepsy in Umbria: A Population-Based Study Using Healthcare Administrative Databases

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