Blog #70: Genetic Testing Can Impact Epilepsy Care

     More and more genes are now known to cause epilepsy. When I was training as a neurology resident in 1970, most epilepsy conditions were thought to be “idiopathic,” i.e., of unknown cause. The origin of most neurological conditions was of unknown cause at that time. We just treated the symptoms of stroke, epilepsy, dementia, etc. However, in 2016, the cause of so many of those conditions can now be identified as definite gene aberrations on our chromosomes. Scientists have sometimes even been able to alter certain genes that cause diseases and improve or even cure the condition.

     Dr. Annapurna Poduri, MD, MPH, Associate Professor of Neurology at Harvard Medical School, reviewed the latest on genetic epilepsy at the 69^th Annual Meeting of the American Epilepsy Society in Philadelphia. Her comments were reviewed in the May 2016 Neurology Reviews. She explained that there are a small but growing number of genes associated with specific treatment recommendations which can allow for precision-medicine-in-epilepsy-treatment. Altered genes have been identified, to date, in 3 percent of genetic epilepsy. An abnormal gene should now be considered as the possible cause in people whose brain scans and medical histories give no clue as to why their epilepsy developed, in contrast to the many people with epilepsy whose brain scans show scars, abnormal blood vessels, tumors, infections, and other changes known to be associated with epilepsy. The SCN1A gene is important in epilepsy. SCN1A-related seizure disorders are inherited in an autosomal dominant manner. For example, half of the offspring of one parent who passed down that gene has a high risk of developing epilepsy, but the risk of developing seizures is not definite since genetic effects are not always manifest even if the abnormal gene is present. Genetic counselors can be very valuable in evaluating for genetic diseases and in interpreting genetic tests. Other epilepsy genes are also being discovered, such as the DNM1 gene—it has been associated with “infantile spasms” and with the Lennox-Gastaut Syndrome.

     Some genes are associated with a benign course of epilepsy. If genetic testing reveals this gene is present, that person can be encouraged that the course of his epilepsy will probably be benign and easily controlled by anticonvulsant medications. This knowledge can provide families and their physicians a degree of diagnostic certainty and reassurance. If the SCN1A-mutated gene in Dravet syndrome is identified, doctors would then know to avoid Lamotrigine (Lamictal) and Phenytoin (Dilantin) because these commonly used antiepileptic medications can worsen these seizures. The GR1N2A gene mutation can cause changes that worsen seizures, but adding Memantine, a drug used in Alzheimer’s Dementia, dramatically reduced the seizures in a child in whom this gene was identified.

     Dr. Poduri concluded that neurologists should pursue genetic testing to give their patients the advantages of the latest genetic discoveries. Better-informed patients can now explore genetic testing with their neurologist to see if it would be appropriate for them.

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.

Blog # 69: A FAMILY DEALS WITH UNRECOGNIZED EPILEPSY

extracted from Dr. Lance Fogan’s novel, DINGS

Chapter 1

Conner’s temperature was one-hundred-three-point-six degrees. I was sitting on the side of our bed and had begun to dial the pediatrician when I heard it. The hairs on the back of my neck bristled. What was that? It was some loud, strange animal sound.

“Arrrgghhrrr!” There it was again!

Sam’s head shot off the pillow, his face cast with a bleary-eyed, quizzical expression.

I dropped the phone. “Conner’s room!” We bolted down the hall. The dim moon through his bedroom window showed our little boy jerking and thrashing on his bed. I pushed past my husband. “What’s he doing? Conner, what are you doing?”

Conner growled. It was a drawn-out, high-pitched cry that sounded like something out of a horror movie.

“Turn on the light, Sam! Conner, what’s wrong?”

Our eight-year-old was on his back, his body twisted in the covers. His head, arms and legs trembled and thrashed; he moaned a long, drawn-out groan between clenched teeth. “Conner, honey. What are you doing? Wake up, Conner!”

“Oh, God! He’s having an epileptic convulsion. I’ve seen ’em before, in Iraq. My brother had one as a kid, too.” Sam bent over and grabbed at Conner’s flailing arms.

“What do we do? What should we do?” Red stains were on the pillow and red-tinged froth bubbled out of my son’s mouth.

“His lips are blue! He’s bleeding! He’s dying! Call Dr. Jackson. No! Call nine-one-one! Sam! Call nine-one-one! It’s an emergency. Hurry! Hurry! We have to get him to the hospital!”

“Stay with him!” Sam turned and ran to the telephone in our room. A few seconds later he was back. “Let’s get Conner in the car. We’ll take him ourselves. It’ll be faster. Let’s go!”

“Yes! Okay! Come on!” Conner had stopped thrashing. He unclenched his jaws and released a long, hissing sigh through foamy pink bubbles on his lips. I detected a faint odor—like urine.

“Conner? Conner, we’re taking you to the hospital, honey.” I stroked his damp forehead and pushed strands of light-brown hair away from his closed eyes. The only sound now was the rattle of his deep, noisy breathing and the roar of my throbbing pulse in my ears. I couldn’t tear my eyes away from the bubbles—pink soap-like bubbles frothing between my son’s lips.

“Ohhhh...” I knelt beside the bed and kissed his sweaty forehead over and over. His tiny hand felt cold and clammy in mine, yet only a few minutes ago he had been burning up with fever, coughing and sneezing.

Sam leaned over Conner. I had never seen my husband look so scared. “I’ll change and get some pants and a shirt on. You’d better get dressed, too, Sandra. We might be at the hospital for hours or...” Our eyes locked on each other.

“Yeah, as soon as you get back.” I pressed my lips. “I’m not leaving him alone.” I saw Grandma Audra’s face—my closest relative that I could recall ever dying. I sat down and cradled Connor’s head in my lap. My body rocked back and forth. Thank God he was breathing. I heard Sam’s dresser drawer squeak and the closet door slam.

When he came back, I left Conner to get dressed but I can’t remember doing it—only my shaking hands.

Sam lifted Conner into his arms. “He’s so light, Sandra.” Sam’s eyes glistened. And this was a man who had returned after a year of combat in Iraq less than two months ago. “Bring another blanket—a dry one. We’ve got to wrap him. It’s cold out.” Sam hefted Conner in his arms a couple of times and headed out of the bedroom. Conner’s bloody, red-lipped face flopped and hung down. I reached to steady his head.

“It’ll be okay. Go get Madison, Sandra. I’ll meet you in the car.” His voice choked, “Hurry!”

I ran to my daughter’s bedroom and lifted the three-year-old out of bed. She opened her eyes wide. She was too surprised to cry, but as I rushed around the room, grabbing clothes and blankets and her stuffed giraffe, her initial surprise erupted into wails of protest. Her mouth was an open cavern; I could see pinkness in the back of her throat.

“Shh, Maddie! Conner’s very sick. We have to take him to the hospital. Be a good girl. We have to go.” She was dry. I took her into the kids’ bathroom and put her on the toilet. Then I put her in some Pull-Ups just in case. The house was quiet. I hurried down the stairs with her and a blanket in my arms.

“No! I don’t want to go! Thtop, Mommy!” the toddler screamed.

“Shush. It’s all right.”

Sam was sitting behind the wheel. Our SUV purred in the garage; its heater was already blowing warm air. Conner, very still now, lay stretched out across the back seat. Madison stopped crying. I strapped her into her car seat and covered Conner. The little girl whimpered again, looked down at her motionless brother and sucked on her Binky pacifier I stuck between her lips. I squeezed into the rear seat and held Conner’s head on my lap.

My tight chest heaved with quick, shallow breaths. Then, I was back in the night that Conner was born. Over eight years ago, just after midnight, like now, Sam drove me to the hospital. Except that night, we were going there so I could deliver Conner. I bent over his face and tasted salt. I rubbed tears from my cheeks. “Oh, Conner. My baby!”

“How’s he doing?” Sam looked back and then forward again. His head turned to the right and to the left as we rolled through a stop sign.

“He’s asleep. Drive faster, Sam! Faster!”

This Southern California March night was chilly. Puffed clouds opened and then closed as they drifted over an almost-full moon that washed light onto the dark, purple distant mountains surrounding our valley.

A few minutes later, we pulled up to the emergency room entrance of the Valley View Medical Center. Madison looked over at me and blinked at the bright hospital lights and the red glowing signs.

Sam put the car in ‘Park’ and pressed on the emergency brake. “Honey, I’ll carry him in. He’s heavy, Sandra.”

“No! I’ll meet you inside. You park and bring Madison!” I gathered Conner into my arms. “I can’t pick him up! Sam! I can’t pick him up!”

“There’s a wheelchair—inside those doors. I’ll carry him to it. You get him in there while I park.” He got out, picked Conner up and carried him through the automatic doors. Sam sat Conner down in the chair and I fixed the blanket over him. Conner’s lips and chin were caked with dried, creased, red smears. He had slumped over an armrest. I propped him back into a sitting position.

“Okay. I’ve got him.”

The doors opened and I heard Madison’s muffled scream from behind her fogged-over window, “Mommy! Mommy!”

White clouds from the tailpipe puffed and floated and then melted into darkness as Sam ran back to the SUV and yelled, “We’ll be with Mommy and Conner in a minute, sweetheart.”

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.

 

Blog #68: Epilepsy, Risks to a Long Life and Mortality

          A study exploring the risks for premature death in the epilepsy community appeared in a recent issue of Neurology.¹ Five hundred fifty-eight people with epilepsy were followed for 25 years. The authors wished to identify predictors of longevity. They found that conditions unrelated to epilepsy caused death in 59 percent (111/189) of the sample: most commonly cancers not related to the nervous system followed by cardiovascular diseases (heart attack, heart failure, etc.) and then cerebrovascular conditions (stroke, etc.). Only 3 percent (6/189) died of their epilepsy, e.g. SUDEP (sudden death in epilepsy), drowning or trauma. 

 

          The death rate was found to be higher in the first two years after the initial seizure, specifically associated with cancers.  Pneumonia was the most common cause of death occurring in 31.2 percent. Males and people who received early epilepsy-control seemed protected against death. This gender difference was surprising since being male is typically associated with having a shorter life-expectancy. More studies need to explore this correlation. Conditions that strongly predicted mortality included brain and non-brain cancers, dementia, Parkinson’s disease, stroke, brain trauma and drug abuse.

          Counseling of the epilepsy population appears to be of primary importance. Physicians’ evaluations can detect malignancies and vascular disease followed by treatment. Medical guidance can prevent many disease-related complications. These non-epilepsy conditions must be addressed just as much as counseling individuals regarding SUDEP (see Blog #13 and Blog #30) or status epilepticus (see Blog # 37).

11    Keezer MR, Bell GS, Neligan A, et. al. Cause of Death and Predictors of Mortality in a Community-Based Cohort of People with Epilepsy. Neurology 2016; 86: 704-12.

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.