Canine detection of volatile organic compounds unique to human epileptic seizure.

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.

Auricular acupuncture for the treatment of nonepileptic seizures: A pilot study.

OBJECTIVE: The aim of this pilot study was to examine the safety and tolerability of an eight-week treatment of twice weekly auricular acupuncture as a therapeutic intervention for the treatment of psychogenic nonepileptic seizures (PNES). The secondary aim was to determine if auricular acupuncture was effective at reducing PNES event frequency. Psychogenic nonepileptic seizures are as common as multiple sclerosis and are highly resistant to intervention. Unfortunately, there is no standard of care therapy, although mental health treatment referrals are commonly made. Acupuncture is felt to be a safe and cost-effective treatment for many diseases and symptoms including mental health disorders such as posttraumatic stress disorder (PTSD), anxiety, and conversion disorders. We propose to examine auricular acupuncture as a treatment for PNES. METHODS: A single-center, 16-week trial of auricular acupuncture was designed: a four-week baseline period, followed by an eight-week active treatment period during which subjects received twice weekly auricular acupuncture, then followed by a four-week washout period. Tolerability was defined as completion of 12 of 16 treatments. Successful compliance with seizure diary was defined as >80%, or 100 of 120 days completed. Safety profile was established and seizure count per week was also calculated. RESULTS: A total of 29 subjects enrolled from a consecutive sample of 73 PNES diagnoses discharging from our epilepsy unit. Twenty-two subjects entered the study with 91% completing more than 12 of 16 treatments, 91% meeting the endpoint of completing >80% of diary entries. Adverse events were mild, and only two subjects were withdrawn due to increased PNES frequency. Although short-term in design, using one-way repeated measures analysis of variance (ANOVA), we observed a statistically significant reduction in seizure count from baseline at treatment month one, treatment month two, and at the washout period (p = 0.0083). Eleven of 12 subjects (52.3%) who received at least one treatment recorded a 50% frequency reduction. Three of 21 subjects (14%) were PNES-free at the end of the study. SIGNIFICANCE: Auricular acupuncture is well-tolerated in a population with PNES and exhibits similar event frequency reductions as cognitive behavioral therapy (CBT). We believe that this is the first literature report examining auricular acupuncture for the treatment of PNES.

The case for medical marijuana in epilepsy.

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/Δ(9) -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.

Diuretics and epilepsy: will the past and present meet?

Clinical 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.

Report of a 6-month-old Asian infant with early infantile epileptic encephalopathy whose seizures were eliminated by cannabidiol.

We observed that cannabidiol supplements were highly effective in treating an infant boy with drug-resistant early infantile epileptic encephalopathy, eliminating his intractable tonic seizures. The infant began suffering clusters of brief tonic seizures from birth at 39 weeks gestation. EEG showed burst-suppression and seizures could not be controlled by trials of phenobarbital, zonisamide, vitamin B6, clobazam, levetiracetam, topiramate, phenytoin, valproate, high-dose phenobarbital, and ACTH therapy. The boy was discharged from hospital at 130 days of age still averaging tonic seizures 20-30 times per day. We started him on a cannabidiol supplement on day 207, increasing the dosage to 18 mg/kg/d on day 219. His seizures reduced in frequency and completely disappeared by day 234. These effects were maintained, with improved EEG background, even after his other medications were discontinued. Cannabidiol's effectiveness in treating drug-resistant epilepsy has been confirmed in large-scale clinical trials in Europe and the United States; however, no such trials have been run in Asia. In addition, no reports to date have documented its efficacy in an infant as young as six months of age. This important case suggests that high-dose artisanal cannabidiol may effectively treat drug-resistant epilepsy in patients without access to pharmaceutical-grade CBD.

History of Migraine Predicts Headache at High Altitude.

Davis, Christopher, Elaine Reno, Edward Maa, and Robert Roach. History of Migraine Predicts Headache at High Altitude. High Alt Med Biol. 17:300-304, 2016.-Objective: To characterize the spectrum of headaches and their association with migraine history within a population of recreational hikers above 4300 m. METHODS: Using a cross-sectional survey design, a convenience sample of 667 hikers participated in a written survey after descent from Mount Gray/Torreys (4349 m). Headaches were characterized as migraine, high altitude headache (HAH), and/or acute mountain sickness (AMS) using International Headache Society Lake Louise AMS scoring criteria. A univariate odds ratio was calculated to determine whether a history of migraine increased the risk of migrainous headache. Multivariate logistic regression was used to assess whether a priori identified risk factors such as age, sex, recent alcohol consumption, home elevation, and self-reported fluid intake and whether summit success increased the risk of any headache at altitude. RESULTS: Sixty percent of hikers were male with an age range of 17-62 years. Eighty percent reached the summit of Mount Grays/Torreys (4349 m). Seventy-nine percent of participants resided in Colorado; the median elevation of residence for subjects was 1697 m (interquartile range 1557-1765 m). HAH occurred in 39% of hikers, while AMS occurred in 26% of hikers. A history of migraine was associated with increased risk of any headache at altitude (OR: 2.49, 95% CI: 1.62-3.65) and was strongly associated with the development of migrainous headache while at altitude (OR: 14.05, 95% CI: 5.49-35.93). CONCLUSIONS: A history of migraine is a risk factor for the development of headache at altitude and is strongly associated with the development of migrainous headache.

Disrobing associated with epileptic seizures and forensic implications.

Little is known about the clinical aspects and medico-legal consequences of disrobing in the context of epileptic seizures. Seizure-related disrobing may occur either as an ictal automatism or during the postictal period. Some patients may experience a seizure while already in the unclothed state, engage in ictal wandering, and thereby appear in public in the nude. Two cases involving disrobing associated with seizures captured via video-monitored electroencephalography are offered. An additional case reveals the legal consequences endured by one patient who experienced a nocturnal seizure and began wandering in an unclothed state. Collectively, these cases illustrate the medical reality of seizure-related disrobing and the related adverse effects on patients' quality of life. Disrobing associated with epileptic seizures carries the potential for serious legal consequences if not properly identified as an ictal phenomenon.

How do you approach seizures in the high altitude traveler?

Counseling patients who suffer first-time or break- through seizures can be difficult, particularly when controllable external factors may be contributing to the lowering of their seizure threshold. High altitude as a potential trigger for seizures is a common question in our epilepsy clinics in Colorado, and this article reviews the existing anecdotal literature, presents our local experience with high altitude seizures (HAS), offers possible mechanisms to explain how high altitude may trigger seizures, and suggests an initial work-up and prophylactic strategies for future high altitude exposures.

Hypobaric hypoxic cerebral insults: the neurological consequences of going higher.

As increasing numbers of people live, work, and play at high altitudes, awareness of the neurological consequences of hypobaric hypoxic environments becomes paramount. Despite volumes of studies examining the pathophysiology of altitude sickness, the underlying mechanisms of the spectrum of altitude related illnesses is still elusive. High altitude headache, acute mountain sickness, high altitude cerebral edema and other neurological presentations including sleep disturbances and seizures at high altitude are reviewed. As our knowledge advances in the field of altitude physiology, the clinical and research techniques developed may help our understanding of hypoxic brain injury in general.

Insulation discontinuity in a vagus nerve stimulator lead: a treatable cause of intolerable stimulation-related symptoms.

Discontinuity in the silicone insulation over an electrode of a left vagus nerve stimulator (VNS) allowed the aberrant leak of current to the phrenic nerve and other structures. This resulted in ipsilateral diaphragmatic dysfunction, inability to vocalize, and severe radiating pain into the jaw and upper incisor for the duration of each stimulation. The device was explanted and a new device was implanted. All stimulation-related symptoms ceased immediately. A similar discontinuity in the silicone insulation is the likely explanation for several prior reports of poorly understood pains and phrenic nerve stimulation in patients with VNSs. The findings and analysis of this case establish a rationale for consideration of replacement of the VNS lead in all similarly symptomatic patients.