Blog #143: Is Your Epilepsy Controlled? If Not, Perhaps There's a Genetic Cause

Advances in genetics have benefited epilepsy and other neurological diseases. Genetics is currently an important part of epilepsy diagnosis. A half century ago, when I was in neurological training, bacterial, fungal, and other identifiable infections and afflictions could be identified. They could be seen in the microscope and in cultures in the laboratory. When these tests and searches were negative, however, we would usually settle on an elusive virus diagnosis. Viral diseases were often difficult to prove. Then, we were so ignorant in dealing with many diseases, as patients know.

Neurogenetic advances over past decades have shown that genetic abnormalities in our bodies can be identified. These advances improve making a diagnosis and can even bring hope for treatment in previously untreatable diseases. Dr. Deepa S. Rajan, Director of the Neurogenetics Clinic at the University of Pittsburgh Medical Center Children’s Hospital teaches that genetics is currently an integral part of neurological disease diagnosis. “Epilepsy and other diseases are being looked at with fresh eyes.”¹

When MRI scans and other sophisticated medical tests show no obvious cause for epilepsy, genetic testing is available. Genetics could show a reason and should be considered. Dr. David Bearden, assistant professor of neurology and pediatrics at the University of Rochester, finds: “If you take all patients with treatment-resistant epilepsy and early-onset epilepsy, we can find a genetic cause in 30-50 percent. However, in kids seizures that respond to the first-line drugs and whose seizures are controlled, a genetic cause usually is not demonstrated.”²

For example, finding the genetic underpinning in an infant with seizures might show the genetic mutation associated with increased or decreased sodium activity in cells. Sodium channel-blocking drugs could benefit one patient whereas another gene could be found associated with decreased sodium channel function; in these patients, blocker-medications should be avoided. Also, genetic knowledge may benefit prognosis and more accurately predict prognosis, “Your child is likely to grow out of this, or not.” The work of understanding the mechanism of genes and genetic pathways is far from complete.

Amyotrophic lateral sclerosis (Lou Gerhig’s disease) that wastes muscles and is usually fatal and Alzheimer’s disease are more common neurological diseases that have benefited from genetic advances.

 

1)    Rajan D.S. Neurology Today: June 2, 2022; pg 8.

2)    Bearden. D. Neurology Today: June 2, 2022; pg 8.

 

 

Lance Fogan, M.D. is Clinical Professor of Neurology at the David Geffen School of Medicine at UCLA. His hard-hitting emotional family medical drama, DINGS, is told from a mother’s point of view. “DINGS” is his first novel. Aside from acclamation on internet bookstore sites, U.S. Report of Books, and the Hollywood Book Review, DINGS has been advertised in a recent Publishers Weekly, New York Times Book Review and the Los Angeles Times Calendar section. DINGS teaches epilepsy and is now available in eBook, audiobook, and soft and hard cover editions.

 

Blog #98: Highlights from the Epilepsy Symposium: University of Southern California. September 15, 2018

Ten percent of the American population will have at least one seizure in their lifetime and one in 26 Americans will develop epilepsy; epilepsy is diagnosed when more than one seizure occurs. Americans with epilepsy number 3.4 million, 65 million people world-wide have epilepsy. There are 48 newly diagnosed cases/100,000 population each year.

• The Communicable Disease Center (CDC) found the death rate for all Americans in 2017 was 844.0 deaths per 100,000 population or 0.84 percent.¹  This statistic is not that dissimilar to the 500 to 1000 deaths per 100,000 people with epilepsy that die each year. However, life-expectancy for people with epilepsy averages 19 years fewer than the general population. In 2014, SUDEP (sudden unexplained death in epilepsy) was listed as cause of death for only 2650 people. Death certificates don’t always list accurate causes of death, but SUDEP is thought to occur in one out of 75-150 Americans, or 30,000, of all ages with epilepsy annually (SUDEP is discussed in my blogs #13, #57 and #68), especially in those whose epilepsy is poorly controlled. Fifty percent of the epilepsy population have more than one seizure/year, i.e., their epilepsy is active and not in remission.
• One-third of the epilepsy population is NOT under the care of a neurologist, the physician-specialty that is more expert in caring for epilepsy patients.
• The greatest number of newly diagnosed patients with epilepsy currently is over 60 years of age, not the pediatric population (see LanceFogan.com blog #15).
• Pregnant women, and those who are considering getting pregnant, should take 400 micrograms of Folic Acid vitamin daily. Folic Acid can lower the incidence of nervous system and other malformations in the fetus. Verbal abilities in children of mothers on antiepileptic drugs (AEDs) who started daily Folic Acid at least four weeks before conception exceed verbal abilities the children of mothers with epilepsy not taking Folic Acid.²

GENETICS IN EPILEPSY:

• Genes that connect with actions of certain anticonvulsants (AED) are now being identified. If these genes are present in the patient a more effective AED can be chosen. Some of these effective medications are not even AEDs but medicines used for other diseases. To date, these genetic laboratories are rare. When two AEDs have been unsuccessful in controlling one’s epilepsy, genetic testing should be done. Genetic testing is expensive, but its use is growing and should benefit many uncontrolled patients. As of 2018, seventy percent of people with epilepsy have no identifiable cause. Genetic screening will probably result in many more identifiable causes.

SURGICAL EPILEPSY TREATMENT:

• Epilepsy is now considered a surgical disease. Epilepsy centers evaluate patients with sophisticated equipment. If an abnormal brain area can be located as the origin of seizures, 60-70 percent are cured of their epilepsy or markedly improved. As scary as brain surgery sounds side effects, as significant thinking, memory, motor or sensory problems, are uncommon. Nonetheless, surgical treatment is underutilized, probably because of fear and expense.

OTHER DEVICES AND TREATMENTS IN EPILEPSY:

• Vagus Nerve Stimulation: in use since 1997. Its effectiveness in decreasing seizures increases over time with its use independent of AEDs. Side effects include cough, hoarseness and shortness of breath because the vagus nerve stimulates these functions of the vocal cords and the respiratory functions. Usually an out-patient procedure.

·         Responsive Neurostimulator: a portion of the external skull surface bone is scooped out for a battery-powered computer (batteries need replacement every 3-5 years) to fit in this bone-bed, then covered with scalp tissue. Thin stimulators are placed into the area of the brain where the seizure originates via two small drill-holes through the skull. Whenever the apparatus detects the beginnings of a seizure the stimulator probes “fire.” This “short-circuits” and halts the seizure. Researchers believe cognition increases over time, probably because fewer seizures occur that interfere with thought. Over one-half of the patients decrease their seizure frequency by 60 percent.

Ketogenic Diet:

            Mostly reserved for intractable epilepsy. Not ideal for good surgical candidates. Effective across the age spectrum. In use since Mayo Clinic doctors in 1924 found this diet efficacious. It consists of 90% of calories from fat and only 10% from carbohydrates (sugars) and protein. The diet is safe and can be effective in children and adults. Ten percent of patients become seizure-free & 40 percent achieve more than 50 percent decrease in seizure frequency at one year. Forty percent remained on the diet at one year due to their successful control. Of 53 percent of the people who discontinued the diet, half was due to poor tolerance and half due to poor seizure control. Response to the diet may take a month to occur.

• Excellent response in most genetic and primary epilepsies (Juvenile Myoclonic, brain malformations and trauma, Dravet, West and Lennox-Gastaut syndromes, infantile spasms, tuberous sclerosis, and others). The ketogenic diet should not be used when certain other conditions exist, usually metabolic diseases.

1)   https://www.cdc.gov/nchs/fastats/deaths.htm 

2)     Husebye ESN, Gilhus NE, Riedel B, et.al. Verbal Abilities in Children of Mothers with Epilepsy. Neurology 2018: 91:e811-e821.

3)     A. Bergqvist in Epilepsy and the Ketogenic Diet; edited  by Stafstrom & Rho, 2004

Lance Fogan, M.D. is Clinical Professor of Neurology at the David Geffen School of Medicine at UCLA. “DINGS” is his first novel. It is a mother’s dramatic story that teaches epilepsy, now available in eBook, audiobook and soft cover editions.