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There is considerable clinical evidence that topiramate (TPM) has a high potential in the treatment of refractory and super-refractory status epilepticus (RSE, SRSE). Because TPM is only approved for oral administration, it is applied as suspension via a nasogastric tube for SE treatment. However, this route of administration is impractical in an emergency setting and leads to variable absorption with unpredictable plasma levels and time to peak concentration. Thus, the development of an intravenous (i.v.) solution for TPM is highly desirable. Here we present data on two parenteral formulations of TPM that are currently being developed. One of these solutions is using sulfobutylether-β-cyclodextrin (SBE-β-CD; Captisol®) as an excipient. A 1% solution of TPM in 10% Captisol® has been reported to be well tolerated in safety studies in healthy volunteers and patients with epilepsy or migraine, but efficacy data are not available. The other solution uses the FDA- and EMA-approved excipient amino sugar meglumine. Meglumine is much more effective to dissolve TPM in water than Captisol®. A 1% solution of TPM can be achieved with 0.5-1% of meglumine. While the use of Captisol®-containing solutions is restricted in children and patients with renal impairment, such restrictions do not apply to meglumine. Recently, first-in-human data were reported for a meglumine-based solution of TPM, indicating safety and efficacy when used as a replacement for oral administration in a woman with epilepsy. Based on the multiple mechanisms of action of TPM that directly target the molecular neuronal alterations that are thought to underlie the loss of efficacy of benzodiazepines and other anti-seizure medications during prolonged SE and its rapid brain penetration after i.v. administration, we suggest that parenteral (i.v.) TPM is ideally suited for the treatment of RSE and SRSE. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: W. Löscher is co-founder and CSO of PrevEp Inc. (Bethesda, MD), which is developing the meglumine-based formulation of TPM. Furthermore, W. Löscher reports consultancy fees from Angelini, AC Immune, Clexio Biosciences, and Lundbeck. Eugen Trinka reports personal fees from EVER Pharma, Marinus, Arvelle, Angelini, Argenx, Medtronic, Bial-Portela & Cª, NewBridge, GL Pharma, GlaxoSmithKline, Boehringer Ingelheim, LivaNova, Eisai, UCB, Biogen, Sanofi, Jazz Pharmaceuticals, and Actavis. His institution received grants from Biogen, UCB Pharma, Eisai, Red Bull, Merck, Bayer, the European Union, FWF Österreichischer Fond zur Wissenschaftsforderung, Bundesministerium für Wissenschaft und Forschung, and Jubiläumsfond der Österreichischen Nationalbank. He is CEO of Neuroconsult Ges. m. b. H. (Salzburg, Austria)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Niemann-Pick C, type 1 (NPC1) is a progressive autosomal recessive neurologic disease caused by defective intracellular cholesterol and lipid trafficking. There are currently no United States Food and Drug Administration approved treatments for NPC1. We undertook a study evaluating the safety, efficacy, and biomarker response of intrathecal 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in a 12-year old subject with mildly symptomatic NPC. The subject received 200mg intrathecal HP-β-CD administered biweekly via lumbar puncture. To date the subject has received 27 intrathecal HP-β-CD injections. Intrathecal HP-β-CD has been generally safe and well tolerated in this subject. There has been an improvement in vertical gaze. The subject has developed subclinical hearing loss at high frequency that is likely HP-β-CD related. Plasma 24-(S)-hydroxycholesterol, a pharmacodynamic biomarker for cholesterol redistribution in the central nervous system, was significantly increased in response to each of the first 5 drug administrations. Further dosing as well as dose escalations are needed to more completely ascertain the safety and efficacy of intrathecal HP-β-CD., (Copyright © 2015 Elsevier Inc. All rights reserved.)