Perampanel: A therapeutic alternative in refractory status epilepticus associated with MELAS syndrome

Santamarina, Estevo; Alpuente, Alicia; Maisterra, Olga; Sueiras, M.; Sarria, Silvana; Guzmán, Lorena; Abraira, Laura; Salas-Puig, Javier; Toledo, Manuel

doi:10.1016/j.ebcr.2019.01.008

Cited by 17 publications

(12 citation statements)

References 11 publications

(15 reference statements)

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“…Abnormal AMPA receptor expression on the cell surface is also known to occur in diseases involving intracellular substance accumulation. The AMPA antagonist perampanel is now recognized as a potentially efficacious drug for progressive myoclonic epilepsies (PME) [112][113][114][115][116][117][118][119][120][121][122][123], a group of rare types of epilepsy, most of which are recognized as intracellular substance storage disorders. Although each of these diseases involves increased intracellular storage of a different pathological substance, their clinical phenotypes are very similar; it is therefore reasonable to consider the existence of several similar AMPA-receptor-related endophenotypes that produce the same clinical phenotype.…”

Section: Genetic Mutations In the Ampa Receptormentioning

confidence: 99%

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

2020

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It is widely accepted that glutamate-mediated neuronal hyperexcitation plays a causative role in eliciting seizures. Among glutamate receptors, the roles of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors in physiological and pathological conditions represent major clinical research targets. It is well known that agonists of NMDA or AMPA receptors can elicit seizures in animal or human subjects, while antagonists have been shown to inhibit seizures in animal models, suggesting a potential role for NMDA and AMPA receptor antagonists in anti-seizure drug development. Several such drugs have been evaluated in clinical studies; however, the majority, mainly NMDA-receptor antagonists, failed to demonstrate adequate efficacy and safety for therapeutic use, and only an AMPA-receptor antagonist, perampanel, has been approved for the treatment of some forms of epilepsy. These results suggest that a misunderstanding of the role of each glutamate receptor in the ictogenic process may underlie the failure of these drugs to demonstrate clinical efficacy and safety. Accumulating knowledge of both NMDA and AMPA receptors, including pathological gene mutations, roles in autoimmune epilepsy, and evidence from drug-discovery research and pharmacological studies, may provide valuable information enabling the roles of both receptors in ictogenesis to be reconsidered. This review aimed to integrate information from several studies in order to further elucidate the specific roles of NMDA and AMPA receptors in epilepsy.

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Section: Genetic Mutations In the Ampa Receptormentioning

confidence: 99%

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

2020

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“…Benzodiazepine [47,51] Gabapentin [47,51] Lacosamide [47,51] Lamotrigine [47,51] Levetiracetam [10,47,51] Oxcarbazepine [10,47,51] Peranpanel [46,47,51] Rufinamide [47,51] Stiripentol [10,47,51] Zonisamide [47,51] Valproic acid-contraindicated in POLG mutations [25,39,51] Vigabatrin-may need to be avoided in patients with mtDNA depletion syndromes [39] Topiramate-may worsen acidosis [39] Phenytoin * [50] Carbamazepine * [50] Phenobarbital * [50] Valproic acid [35] Phenobarbital [35] Lamotrigine [35] Phenytoin [35] Carbamazepine [35] Oxcarbazepine [35] Vigabatrin [35] Tiagabine [35] Gabapentin [35] Pregabalin [35] * Toxic effect on mitochondria outweighs the beneficial effect.…”

Section: Mitochondria-safe Aeds Aeds To Use Carefully Aeds Which Could Aggravate Myoclonusmentioning

confidence: 99%

Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

2021

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Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease.

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“…The outcome of mitochondrial status epilepticus is poor 99. Perampanel has been recently suggested as a potential therapeutic alternative in refractory status epilepticus associated with MELAS 100. Intravenous magnesium as anticonvulsant therapy, adapted from practice in eclampsia, was attempted in two unrelated, previously healthy teenage girls who developed refractory status epilepticus 101.…”

Section: Treatment Of Specific Clinical Featuresmentioning

confidence: 99%

Mitochondrial disorders and drugs: what every physician should know

Orsucci¹,

Ienco²,

Siciliano³

et al. 2019

DIC

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Mitochondrial disorders are a group of metabolic conditions caused by impairment of the oxidative phosphorylation system. There is currently no clear evidence supporting any pharmacological interventions for most mitochondrial disorders, except for coenzyme Q10 deficiencies, Leber hereditary optic neuropathy, and mitochondrial neurogastrointestinal encephalomyopathy. Furthermore, some drugs may potentially have detrimental effects on mitochondrial dysfunction. Drugs known to be toxic for mitochondrial functions should be avoided whenever possible. Mitochondrial patients needing one of these treatments should be carefully monitored, clinically and by laboratory exams, including creatine kinase and lactate. In the era of molecular and ‘personalized’ medicine, many different physicians (not only neurologists) should be aware of the basic principles of mitochondrial medicine and its therapeutic implications. Multicenter collaboration is essential for the advancement of therapy for mitochondrial disorders. Whenever possible, randomized clinical trials are necessary to establish efficacy and safety of drugs. In this review we discuss in an accessible way the therapeutic approaches and perspectives in mitochondrial disorders. We will also provide an overview of the drugs that should be used with caution in these patients.

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Perampanel: A therapeutic alternative in refractory status epilepticus associated with MELAS syndrome

Cited by 17 publications

References 11 publications

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors

Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

Mitochondrial disorders and drugs: what every physician should know

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