Summary Charlotte, a little girl with SCN1A‐confirmed Dravet syndrome, was recently featured in a special that aired on CNN. Through exhaustive personal research and assistance from a Colorado‐based medical marijuana group (Realm of Caring), Charlotte's mother started adjunctive therapy with a high concentration cannabidiol/Δ9‐tetrahydrocannabinol (CBD:THC) strain of cannabis, now known as Charlotte's Web. This extract, slowly titrated over weeks and given in conjunction with her existing antiepileptic drug regimen, reduced Charlotte's seizure frequency from nearly 50 convulsive seizures per day to now 2–3 nocturnal convulsions per month. This effect has persisted for the last 20 months, and Charlotte has been successfully weaned from her other antiepileptic drugs. We briefly review some of the history, preclinical and clinical data, and controversies surrounding the use of medical marijuana for the treatment of epilepsy, and make a case that the desire to isolate and treat with pharmaceutical grade compounds from cannabis (specifically CBD) may be inferior to therapy with whole plant extracts. Much more needs to be learned about the mechanisms of antiepileptic activity of the phytocannabinoids and other constituents of Cannabis sativa.
Objective: Literature accounts of service dogs alerting patients prior to their seizures are a mix of historically poor quality data and confounding diagnoses. In a group of epilepsy patients, Canine Assistants and Florida International University characterized a unique scent combination of volatile organic compounds present during the immediate postictal period, but never at other times. The current study was designed to confirm prospectively if this unique scent, and potential biomarker, can: (1) be detected in an epilepsy monitoring unit (EMU), (2) whether this scent is present with nonepileptic seizures, and (3) whether this scent also precedes the clinical-electrographic seizure. Methods: Following consent and approval, sweat samples taken from EMU admissions at Denver Health Medical Center were sent to Canine Assistants in Georgia. Their team of service dogs, who had been imprinted to recognize the unique scent, were then asked to process these sweat samples in a simple yes/no identification paradigm. Results: Sixty unique subjects were enrolled over a two-year period. In the first part of this study, a total of 298 ictal sweat samples of 680 total observations were collected. The dogs had a 93.7% (OR: 14.89, 95% CI: 9.27, 23.90) probability of correctly distinguishing between ictal and interictal sweat samples. In the nonepileptic seizure population, 18 of the 19 NES events that were accompanied by sweat sample collections were not associated with identification of the unique seizure scent. In the second part of the study, in which subjects had samples collected every hour, dogs identified the unique seizure scent presence before 78.7% of all seizures captured, at a probability of 82.2% (OR: 4.60, 95% CI: 0.98, 21.69) of a positive detection predicting a seizure. The average duration of the warning phase of the scent was 68.2 min. The average duration of the tail phase of the scent faded after 81 min. Significance: This study confirms the unique seizure scent identified by Canine Assistants and FIU may be collected and recognized by dogs trained to do so, in a prospective manner. A significant number of seizures appear to be associated with the unique scent presence prior to clinical-electrical onset of the seizure itself, and therefore further study of this biomarker is warranted.
SUMMARYClinical studies from over half a century ago suggested efficacy of a variety of diuretics in focal and generalized epilepsies as well as in status epilepticus, but these findings have not been translated into modern epilepsy training or practice. Recent advances in our understanding of neuronal maturation and the pathophysiology of neonatal seizures provide fresh insight into the mechanisms by which diuretics might reduce susceptibility to seizures. In vitro and in vivo rodent studies and human epilepsy surgical cases have shown that specific diuretic agents targeting the cation-chloride cotransporters decrease neuronal synchrony and neuronal hyperexcitability. These agents are thought to convey their antiepileptic activity by either expanding the extracellular space or promoting a cellular chloride transport balance that reflects a more developmentally ''mature,'' less excitable state. It may be time to reexamine whether diuretics could serve as adjunctive therapies in the treatment of refractory epilepsies.
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