Abstract
Seizures in 20-30% of epileptics are resistant to treatment with anti-epileptic drugs (AED). This chapter evaluates studies on the efficacy of cannabinoids as adjunctive therapy for control of intractable seizures, with a focus on developmental epileptic encephalopathies (DEE). A systematic review conducted by literature search through PubMed, EBSCO, and ProQuest electronic databases identified 16 studies in the last seven years. Moderate- to low-certainty of evidence supports the benefits of cannabinoids in reducing seizure frequency, intensity, duration, and epileptics' overall condition in many types of intractable seizures. Studies used either synthetic cannabidiol (CBD), highly purified plant-derived CBD (Epidiolex®), or less pure cannabis plant-based CBD oils, and extended over months to two years. Drug interactions of ingested CBD with concomitant valproate and clobazam could be avoided with sublingual CBD. Five percent of patients became seizure free. Future studies are warranted to optimize the anti-seizure effects of emerging cannabinoid treatment strategies.
TopBackground
Treatment regimens recommended by the International League Against Epilepsy (ILAE) vary by the type of seizures which are operationally classified based on (a) onset – focal seizures (auras in which electrical impulses begin in just one area of the brain), generalized seizures (begin in both hemispheres and may lead to loss of consciousness), or seizures of unknown onset, (b) level of awareness – seizures while alert, or seizures with impaired awareness, and (c) by whether movements occur or not – motor seizures include automatisms, atonic (temporary loss of muscle tone that could cause abrupt falls), clonic (repeated jerking of arms and legs), epileptic spasms (clusters of brief sudden muscle stiffening), hyperkinetic, myoclonic (sudden muscle jerks), tonic (stiffening of the body), tonic-clonic (muscle stiffness and rhythmic convulsions), myoclonic-atonic, myoclonic-tonic-clonic, with drop seizures defined as either atonic, tonic, or tonic–clonic seizures involving the entire body, trunk, or head that could lead to a fall, injury, or slumping in a chair, while non-motor seizures include autonomic, behavior arrest (decrease or arrest of motor activity), cognitive (alteration in cognition), emotional (bursts of laughter, crying, panic, ecstasy, or anger), sensory (visual, auditory or tingling sensations), eyelid myoclonia, typical absence (sudden trance-like state lasting few seconds) and atypical absence (staring episodes lasting more than 10 seconds with eye blinking, chewing, lip smacking or finger rubbing movements) (Fisher et al. 2017a,b).
Key Terms in this Chapter
Lennox-Gastaut Syndrome (LGS): Epilepsy in which developmental delays, cognitive impairments or behavioral problems may precede the appearance in early childhood of a combination of tonic, atonic and atypical absence seizures with a characteristic pattern of slow spike-and-wave activity on EEG.
Electroencephalography (EEG): A method of measuring and tracing electrical activity detected from the brain to record brain wave patterns.
Tuberous Sclerosis Complex (TSC): A disease in which benign tuber-shaped tumors develop within multiple organs including the brain, and give rise to seizures, caused by mutations in either the TSC 1 gene for hamartin or the TSC2 genes for tuberin.
Dravet Syndrome: An epilepsy syndrome with gait abnormalities and intellectual disability, previously called severe myoclonic epilepsy of infancy.
International League Against Epilepsy (ILAE): Was founded in 1909 and is an organization of more than 120 national chapters. The ILAE strives to provide definitions for key concepts and classification schemes to help in developing a common language and new treatments.
Sudden Unexpected Death in Epilepsy Patients (SUDEP): Sudden unexplained deaths in people with epilepsy that occur without warning and for which no cause of death is found.
Status Epilepticus: A life-threatening medical emergency during which either a seizure lasts longer than 5 minutes, or multiple seizures occur within a 5-minute period without intervening recovery of normal consciousnesses levels.