How to treat epilepsy?
By Ibani Kapur, Farooq Ali Khan, Abhishek Kumar, Raamesh Gowri Raghavan, and Sukant Khurana
History –
The disease of Epilepsy has been understood only for a few decades now. However the disease has been plaguing humans ever since civilisation began. Earliest records can be found in Assyrian texts (2000 B.C) and in Babylonian records (1067–1046 B.C). The Babylonian records showed detailed accounts of the signs, symptoms and treatment for the disease. They also gave a description of the different types of Epilepsy. But since in those days there was no medical knowledge or skills available, the cause of the disease was attributed to religious and spiritual phenomenon. This type of view of Epilepsy was first challenged by Hippocrates who in 5th century B.C identified the brain to be the reason for the disease and in his book; On the Sacred Disease claimed that the disease like any other disease, cannot have a divine origin. Before Hippocrates, the Greek believed that the disease had a spiritual nature and was caused due to the moon Goddess. Also, there were also periods of time when it was believed that Epilepsy was a mark of intelligence and prophetic powers. The first electrical basis for the disease was proposed by Robert Bentley Todd in 1849 and it was theorized by John Hughlings Jackson in 1873 that the Epileptic seizures were due to an energy discharge through the whole body. While Todd’s theory called the energy to be electrical in nature, Jackson only claimed it to be energy of some kind. In the 1930s the EEG was discovered by Hans Berger and the energy was found to be electrical in nature and the cause was found to be the brain. The first drug to treat epilepsy was found in 1939 and until now various discoveries were made on the cause and the treatment for Epilepsy.
Description –
Epilepsy is the fourth most common neurological disorder and it affects people of all ages. It is a chronic condition and is characterised by seizures. The condition includes a wide variety of seizure types and hence can be considered as a spectrum disorder. The nerve cells in our brain control every function of our body. The control of function occurs by the passing of signals from one cell to another. The signals are electronic in nature and consist of transmission of ions across and between the cells. When the transmission between the cells become abnormal, then it results in a seizure. Depending on which nerve cell transmission is affected, the seizure varies and can cause disturbance of motor, sensory, mental or emotional functions. In the brain there are signals to cause the excitation/ activation of the functioning of the cells and also signals to cause the inhibition/ deactivation of the functioning of the cells. Under normal conditions, there exists a balance between these two types of signals. Thus, just like a computer, by alternatively turning on and off of the cells, the brain also functions and allows our body to perform various activities. But during a seizure, this balance is lost and hence the normal functioning of the neurons is lost and the signalling goes haywire. Seizures usually have three stages of occurrence — a beginning, a middle and an end. Some people have an additional stage in the beginning called the Prodromal stage.
i. Prodromal stage — occurs days, weeks or several hours before the actual seizure. These are not actually a part of the seizure itself but are premonitions and initial symptoms that indicate a coming seizure. This could include behavioural changes, mood changes, anxiety, cognitive disturbances
ii. Aura — this stage occurs a few seconds or hours before the onset of the seizure. Sometimes an aura could even be a partial seizure on its own. The symptoms of an aura vary from person to person. Most common symptoms include those of the motor, somatosensory, visual and auditory symptoms. It occurs due to the activation of functional cortex by abnormal, unilateral and brief neuronal discharge. The symptoms of the aura, in addition to informing of a coming seizure, can also be used to find the location of the seizure causing disturbance.
iii. Ictal phase — it is the middle phase of seizure and is the most active part of seizure. It is the phase of seizure that is visible on the outside. It can be either convulsive or non-convulsive in nature.
iv. Post Ictal phase — this stage occurs after the seizure and is characterised by after effects of the seizure. During this stage people often find it difficult to concentrate and may feel disoriented. The symptoms could last for about 15 to 36 hours. Depending on the location of the seizure activity in the brain, the symptoms of this phase will change. There is possibility of loss of motor function and can also sometimes lead to paralysis. If the abnormal electrical activity was in the sensory cortex of the brain, then there is possibility of loss of sensory function also.
Epidemiology
It is estimated that about 7–8 percent of the population experiences
Atleast one epileptic seizure is experienced by 7–8 percent of the population.
In United States 0.5–1 percent of the population is affected with incidence 30.9–56.8 per 100,000. (1)
Classification of Seizures
The International League Against Epilepsy classifies seizures as partial and primary generalised seizures
Partial seizures occur with their focal point in a localised area within the cerebral hemisphere as indicated by an EEG. These seizures can be further categorised as simple or complex. Complex seizures are associated with loss of consciousness. Simple seizures are confined to the neocortical structures and are less disabling compared to partial seizures.(1)
Primary generalised seizures have their origins in both the cerebral hemispheres simultaneously. These types of seizures can be traced to a genetic factor, occurring at a younger age. These are not attributed so much to brain lesions as are other types of seizure disorders like tumours,infections,traumatic brain injury and other developmental abnormalities. (1)
Structural Imaging
For high-resolution structural imaging, MR imaging is the most preferred choice although CT scan is also in use. Since Partial complex epilepsy requires scrutiny of hippocampus and temporal lobe, high field scanners are necessary to evaluate these. MRI imaging is an essential procedure for evaluation of epilepsy before surgery. However, in many patients structurally detectable abnormalities are absent. In such conditions, there is a requirement of functional techniques like(1)
positron emission tomography(PET),
single-photon emission CT(SPECT),
magnetic source Imaging (MSI) and
functional MR imaging (fMRI)
Neuropsychiatric co-morbidities of epilepsy
Depression- Symptoms of depression are exhibited in between 10 to 60 percent of epilepsy patients. Deficiency of serotonergic transmission is a major cause of depression such patients. The mechanism leading to the condition of depression can be attributed to inflammation as many inflammatory biomarkers are detected.(2)
Memory Impairments- Memory and cognitive impairments are other common traits which are often observed in epileptic patients. Some of the causes of these impairments are –
1) Neuronal hippocampal cell loss
2) Dysfunction of surviving hippocampal neurons
3) Adverse effects of anti epileptic drugs (2)
Autism spectrum disorder — Mechanisms responsible for autism are related to genetic as well as environmental factors. Maternal infection has been found to pose a major risk of autism in the offspring. Autism spectrum disorder is one in which there is a diminished communication between hippocampus and prefrontal cortex (2)
TREATMENT FOR EPILEPSY-
Epilepsy as a disease cannot be cured in a literal sense of the word but its effects can be controlled. Its symptoms can and should be kept in check at all times. For this reason, anti-epileptic drugs can be used to manage the seizures. Some anti-epileptic drugs used are as follows,
1. Brivaracetam- Anticonvulsant/ Antiepileptic — used to treat people having seizures on only one part of the brain — partial onset seizure. Trade name for this drug is Briviact. It is to be taken twice everyday if administered orally while if given in form of Intravenous drug, the infusion into the vein is to be for 2 to 15 minutes.
2. Carbamazepine — Anticonvulsant — It works by reducing some responses in the brain. The dosage of the drug varies according to the type of epilepsy and the age of the affected person.
3. Divalproex — Anticonvulsant — It is prescribed for Epilepsy, Bipolar Disorder and migraine headaches. It controls abnormal activity in brain and CNS. Dosage again depends on the age of the person and the type of epilepsy and symptoms experienced.
4. Ethosuximide — Anticonvulsant — it controls abnormal electrical activity in brain. Zarontin is the trade name for the drug in India.
RECENT DISCOVERY –
Path followed by seizure in neurons — Researchers in Columbia University recently discovered that regardless of the speed of the seizure, the path followed by it is the same. This means that, seizures, however fast or slow they are, will always travel from one cell to the next. This disproves the long held belief that seizures are due to random firing of cells. Also this is the first time scientists have seen cell to cell seizure activity.
Cannabidiol compound effect on Dravet Syndrome — Dravet Syndrome is a severe form of Epilepsy affecting children. A trail conducted in Ann & Robert H. Lurie Children’s Hospital of Chicago, found that about 93 percent of the children with Dravet Syndrome given a cannabidiol had fewer seizures. Cannabidiol is a cannabis compound that does not contain the psychoactive properties of marijuana.
Micro-gene and Epilepsy — Researchers in the Hebrew University found that excess of micro-RNA leads to the individual being hyper sensitive to Epilpesy-inducing compounds.
References
1) ACR APPROPRIATENESS CRITERIA
J.P. Karis, for the Expert Panel on Neurologic Imaging
2) Epilepsy and brain inflammation
Annamaria Vezzani , Eleonora Aronica , Andrey Mazarati, Quentin J. Pittman
3) Engel, Jerome Jr. (1989), Seizures and Epilepsy, Philadelphia: F.A. Davis Company, ISBN 0–8036–3201–0
4) Fisher, RS; Schachter, SC (2000), “The Postictal State: A Neglected Entity in the Management of Epilepsy.”, Epilepsy & Behavior, 1 (1): 52–59,doi:10.1006/ebeh.2000.0023, PMID 12609127
5) Devinsky, O (2008), “Postictal Psychosis: Common, Dangerous, and Treatable”, Epilepsy Currents, 8 (2): 31–34, doi:10.1111/j.1535–7511.2008.00227.x, PMC 2265810
6) https://epilepsytalk.com/2016/01/18/the-four-stages-of-seizures-prodromal-auras-ictal-and-postictal/
7) http://www.uchospitals.edu/specialties/neurosciences/epilepsy/seizure/stages.html
8) Marco, Mula,; Francesco, Monaco,. “Ictal and Peri-Ictal Psychopathology”. Behavioural Neurology. 24 (1). doi:10.3233/ben-2011–0314. ISSN 0953–4180.
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11) http://www.emedicinehealth.com/epilepsy/article_em.htm
12) https://medlineplus.gov/epilepsy.html
13) http://www.epilepsy.com/learn/epilepsy-101/what-epilepsy
14) http://www.indianepilepsycentre.com/faqs-treatment.html
15) http://www.medindia.net/drugs/medical-condition/epilepsy.htm
16) https://www.sciencedaily.com/news/health_medicine/epilepsy/
17) Michael Wenzel, Jordan P. Hamm, Darcy S. Peterka, Rafael Yuste. “Reliable and Elastic Propagation of Cortical Seizures In Vivo”. Cell Reports, 2017; 19 (13): 2681 DOI: 10.1016/j.celrep.2017.05.090
18) Orrin Devinsky, J. Helen Cross, Linda Laux, Eric Marsh, Ian Miller, Rima Nabbout, Ingrid E. Scheffer, Elizabeth A. Thiele, Stephen Wright. “Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome”. New England Journal of Medicine, 2017; 376 (21): 2011 DOI: 10.1056/NEJMoa1611618
19) Uriya Bekenstein, Nibha Mishra, Dan Z. Milikovsky, Geula Hanin, Daniel Zelig, Liron Sheintuch, Amit Berson, David S. Greenberg, Alon Friedman, and Hermona Soreq. “Dynamic changes in murine forebrain miR-211 expression associate with cholinergic imbalances and epileptiform activity”. PNAS, 2017 DOI: 10.1073/pnas.1701201114
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About:
Dr. Sukant Khurana runs an academic research lab and several tech companies. He is also a known artist, author, and speaker. You can learn more about Sukant at www.brainnart.com or www.dataisnotjustdata.com and if you wish to work on biomedical research, neuroscience, sustainable development, artificial intelligence or data science projects for public good, you can contact him at skgroup.iiserk@gmail.com or by reaching out to him on linkedin https://www.linkedin.com/in/sukant-khurana-755a2343/.