Faculty Bibliography

In the past two decades, there has been an increasing interest in the therapeutic potential of cannabinoids for neurological disorders such as epilepsy, multiple sclerosis, pain, and neurodegenerative diseases. Cannabis-based treatments for pain and spasticity in patients with multiple sclerosis have been approved in some countries. Randomised controlled trials of plant-derived cannabidiol for treatment of Lennox-Gastaut syndrome and Dravet syndrome, two severe childhood-onset epilepsies, provide evidence of anti-seizure effects. However, small clinical trials of cannabinoids in other neurological disorders such as Huntington's disease, attention deficit hyperactivity disorder, and dementia, have not found any effect. Despite positive results in these two severe epilepsy syndromes, further studies are needed to determine if the anti-seizure effects of cannabidiol extend to other forms of epilepsy, to overcome pharmacokinetic challenges with oral cannabinoids, and to uncover the exact mechanisms by which cannabidiol or other exogenous and endogenous cannabinoids exert their therapeutic effects.

OBJECTIVE:receptors with minimal activity at α1-containing receptors, which are believed to mediate many of the adverse events associated with benzodiazepines, in the epilepsy photosensitivity model as a proof-of-principle of efficacy. METHODS:Seven participants with a photoparoxysmal response to intermittent photic stimulation (IPS) at baseline were randomized in a double-blind, 4-period cross-over study examining single doses of 17.5 and 52.5 mg PF-06372865, 2 mg lorazepam (active control), and placebo. Standardized photosensitivity ranges (SPRs) to IPS were recorded at screening, predose, and 1, 2, 4, and 6 hours postdose. The primary endpoint was the average least squares mean change in the SPR in the participant's most sensitive eye condition, across all time points. RESULTS:Both doses of PF-06372865 produced a marked and statistically significant mean reduction in SPR compared to placebo, which was similar in degree to lorazepam. There was complete suppression of SPR in 6/7 participants following PF-06372865 or lorazepam administration. PF-06372865 was safe and well-tolerated. CONCLUSION/CONCLUSIONS:PAM in humans. Further study of the antiepileptic properties of PF-06372865 is warranted. CLINICALTRIALSGOV IDENTIFIER/UNASSIGNED:NCT02564029. CLASSIFICATION OF EVIDENCE/METHODS:This study provides Class II evidence that for people with a stable photoparoxysmal response to intermittent photic stimulation, PF-06372865 reduces the SPR.

Over half a million women of childbearing age have epilepsy, many of which will require family planning care at some point in their reproductive years. Matters relating to contraception, pregnancy, fertility, and sexual functioning are all impacted to varying degrees by the use of antiepileptic drugs (AEDs) to treat epilepsy and require active management by a woman's neurologist. It is important that a woman's obstetrician/gynecologist (OBGYN) and internist are aware of the way in which their care may be related to her epilepsy care and how this can be successfully comanaged with her neurologist. This includes the impact AED therapies have on pregnancy, such as risk of teratogenicity, changes to AED clearance rates during pregnancy and postpartum, and risk of seizure worsening while pregnant; interactions of hormonal contraceptives and AEDs; side effects of AED treatment on hormonal systems and sexual functioning; and matters of fertility and infertility treatments. The current editorial discusses these relationships between AED choice, dose, and family planning matters for women with epilepsy in their childbearing years to support the collaboration of care between her neurologist, OBGYN, and internist.

This companion paper to the introduction of the International League Against Epilepsy (ILAE) 2017 classification of seizure types provides guidance on how to employ the classification. The classification is illustrated by tables, a glossary of relevant terms, a table mapping old to new terms, recommended abbreviations and examples. Basic and extended versions of the classification are available depending on the desired degree of detail. Key signs and symptoms of seizures (semiology) are used as a basis for categorization of seizures that are focal or generalized from onset or with unknown onset. Any focal seizure can be further optionally characterized with respect to whether awareness is retained or impaired. Impaired awareness during any segment of the seizure renders it classified as a focal impaired awareness seizure. Focal seizures can be further optionally characterized by the first motor signs and symptoms as atonic, automatisms, clonic, epileptic spasms, hyperkinetic, myoclonic or tonic activity. Nonmotor onset seizures can be manifested as autonomic, behavior arrest, cognitive, emotional, or sensory dysfunction. The earliest prominent manifestation defines the seizure type, which can then further progress to other signs and symptoms. Focal seizures can become bilateral tonic-clonic seizures. Generalized seizures include an early involvement of bilateral networks from the onset. Generalized motor seizure characteristics comprise atonic, clonic, epileptic spasms, myoclonic, myoclonic-atonic, myoclonic-tonic-clonic, tonic or tonic-clonic manifestations. Nonmotor (absence) seizures are typical or atypical or seizures that present prominent myoclonic activity or eyelid myoclonia. Seizures of unknown origin may have features that can still be classified as motor, nonmotor, tonic-clonic, epileptic spasms or behavior arrest. This users' manual for the ILAE 2017 seizure classification can assist the acceptance of the new system.

The International League Against Epilepsy (ILAE) presents a revised operational classification of seizure types. The purpose of this revision is to recognize that some seizure types can have either a focal or generalized onset, to enable a classification when the onset is unobserved, to include some missing seizure types and to implement a more transparent and understandable nomenclature. Because current knowledge is insufficient to form a scientifically based classification, the 2017 classification is operational (practical) and based on the 1981 classification with the amendments from 2010. The changes include the following: (1) "partial" becomes "focal"; (2) awareness (disturbance of consciousness) is used as a classification criterion of focal seizures; (3) the terms dyscognitive, simple partial, complex partial, psychic and secondarily generalized are eliminated, (4) new focal seizure types include automatisms, behavior arrest, hyperkinetic, autonomic, cognitive, and emotional, (5) epileptic spasms as well as atonic, clonic, myoclonic and tonic seizures can have a focal or generalized onset, (6) focal (seizure with progression) to (a) bilateral tonic-clonic seizure replaces secondarily generalized seizure, (7) new generalized seizure types are absence with eyelid myoclonia, myoclonic absence, myoclonic-atonic, myoclonic-tonic-clonic seizures and (8) seizures of unknown onset may have features that can still be classified. The new classification does not represent a fundamental change but enables greater flexibility and transparency in naming seizure types.