After 40 Years without Grand Mal Epilepsy Attacks and Despite Regular use of Antiepileptic Drugs, the Patient with a Comatose Attack Suddenly

Dr. Hassan Jazayeri ^*

*Correspondence to: Dr. Hassan Jazayeri, neurologist.

Copyright

© 2024 Dr. Hassan Jazayeri. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received: 12  February 2024

Published: 01 March 2024

DOI: https://doi.org/10.5281/zenodo.10847981

An incredible report

After 40 years without grand mal epilepsy attacks and despite regular use of antiepileptic drugs, the patient with a comatose attack suddenly..

 

A simple event

It was very new and strange to me that, after several decades of working with neuropsychological patients, and of course visiting and monitoring them, the patient, after 40 years of not having a grand mal seizure, suddenly had such a severe attack that, in a comatose state, the patient was taken to the ward. He is taken to the emergency room of the hospital. This incident happens while he is asleep and in the middle of the night. The patient wakes up with a state of suffocation and excitement and then goes into a deep coma. He was transferred and after four hours in the hospital, while he was under the monitor, when he opened his eyes, he asked his companions who were impatiently worried about his condition.

... where is here ? where am I? What am I doing here? Isn't it dinner time and…

The fact is that when I encountered this 65-year-old man in that critical state, it was absolutely unbelievable for me that it was a grand mal epileptic attack. Especially the fact that he was almost 40 years attack-free. In this long time, he didn't even have brief moments  of Aura . . Of course, during this period, this patient has been under medical treatment with 500 mg Valproic Acid  tablets twice a day. He was admitted to Nene Teresa Hospital No. 5, and after initial examinations, he came out of coma and was able to talk to the people around him and the medical staff. While no one knew how this problem happened. He only knew that he was taken to the hospital. Later, in the neurology department, a brain scan was taken from him, and it was determined that this was a recurrence of Grand Mal's epilepsy, which happened after four decades! . A very rare and important event. Then with E.E.G was performed,

We could not determine the reason for the recurrence of this attack. Especially me, who had known the patient for many years. Not a new concussion, not an acute infection, not even a history of chronic covid 19, not a nervous crisis, not sleep disorders, not psychotic crises, not intense physical activity, not metabolic changes, not using a new drug and... none of them. They could not justify the cause of the new attack, with such severity that it would put him in a coma for four hours.

This attack still remains in an aura of uncertainty and question for me and my colleagues. When I faced this rare case, I decided to prepare it as a report and experience and make it available to my colleagues.

 

Figure 1

 

What basic information do we have about epilepsy?

We have the following details about grand mal epilepsy:

1.According to the World Health Organization (WHO) , it is estimated that up to %70   of people with Grand Mal epilepsy will live without seizures if diagnosed and treated properly .

2.The risk of premature death in people with grand mal epilepsy is three times higher than in the general population .

3. Grand mal epilepsy accounts for a significant part of the disease burden in the world and affects about  50 million people worldwide .

4.Approximately  2.2 million Americans live with grand mal epilepsy .

5.Grand mal epilepsy is the fourth most common disease in the world, which is included in the classification of brain and nerve diseases.

 

Experience working with epileptic patients

My personal experience in working with grand mal epilepsy patients is that, when patients' seizures are controlled by drug therapy, they often wonder when they will be free from taking anti-epileptic pills, and always when they are free for a while. They are attacked, they want their doctor to  stop the medicine. And this is an endless story of all epilepsy in all countries.

I never, at any time, even if I wanted to stop taking anti-epileptics, I would not do it suddenly and all at once I believed that the low tappering method should be used and I still believe that.

 

Categories of Siezures

Dr. Jacqueline French, a neurologist and epilepsy specialist at  NYU Langone Medical Center in New York , say:

Epilepsy in four hands Main Classification may be       

•epilepsy Ideopathic or primary which is not associated with other neurological diseases and has no known cause except genetic basis. Statistically, these epilepsies include the least number of epilepsies
•Acquired   (or secondary) epilepsy can be caused by complications  during pregnancy, traumatic brain injury, stroke, tumors and diseases of the brain and nerves , including infections.

In both cases, epilepsy symptoms occur because normal signaling between nerve cells and the brain is disrupted, possibly due to an abnormality in the brain's wiring or an imbalance of nerve signaling chemicals called neurotransmitters, or a combination of the two. According to D. French, sometimes epileps   is started several years after  damage to the brain Researchers tried to find a way to diagnose before seizures attacks. But all of them has been failed. While the main symptom of epilepsy is seizures, having seizures does not necessarily mean having grand mal epilepsy.

 

Risk factors:

The known risk factors for grand mal epilepsy are:

Severe head injury, especially direct trauma

Previous cerebral stroke.

Brain parenchymal hemorrhages

The presence of space-occupying lesions in the brain such as cysts or tumors

High fevers in children

Complications during childbirth or difficult childbirth

 

Reduce or stop medication?

Usually, patients who do not have an attack for more than three years of drug treatment, it is a well-known method to decide to reduce the drug dose and stop the drug after six months.

I always advised my patients, even if you don't have any problems after stopping the medicine, to inform me with a short SMS so that we don't face the new side effects of stopping the medicine suddenly.

This encouraged the patients to be fully sensitive to this issue. I remember well that one of my neurologist colleagues in Iraq said:

I (meaning him) face the patient's request to stop the medicine. Because the patient said that he has not had an epileptic attack for more than four years. For this reason, the patient insisted that I stop his medication. This was done and the patient even got his driver's license back from the police.

But it didn't take long to cost him his life. The story was that on the free way where I was driving, I noticed a car accident in my hundred. I saw all the untimely movements of the car and it was strange to me that the driver of the car kept pulling to the right and left and finally entered the free way with another A car carrying drinking water crashed. When I reached the car that had crashed, I recognized my patient in complete disbelief and became certain that the cause of the car crash was due to the epileptic seizure of the driver.

 

The project of reducing or discontinuing drugs for epilepsy patients:

It was in early April 2023 that some of my epileptic patients, whose epileptic causes were secondary to direct or indirect traumas and were under drug treatment and did not have an attack, had sporadically requested me to stop using drugs for them. I will check and if I agree, I will stop their anti-epileptic treatments

With this idea, considering that these patients had not had an attack for many years and I had a complete knowledge of them, I first agreed to investigate the issue. The total number of these patients was 29 and their age group was between 43 and 76 years old. All of them were male acses.

 

Motivation for working on the drug adjustment project for epilepsy patients

My main motivation for working on this project was:

• Some of these patients had elevated liver enzymes due to the use of anti-epileptic drugs. Despite expert investigations to find the cause of elevated liver enzymes, we did not reach a diagnosis other than that it may be a drug complication.
• The cause of their epilepsy was almost secondary epilepsy caused by traumas recorded several years ago.

we also had cases, for example, while driving and crossing the railway tracks in West Germany, he collided with a train and was in a coma for several days, and then gradually returned to normal

The same patient who was facing multiple attacks in the past years and his condition was not controlled even with a single drug and was treated with carbamazepine and valproic acid, now says: I have not had an attack for more than two years. So why should I take medicine?

And he stopped his medicine without consulting any doctor.

• In these reviews, we did not primarily focus on children and focused on adults who had been treated with antiepileptic drugs for many years

We know that epilepsy types, approximately two-thirds of patients react to any type of medication , while one-third of patients are drug - resistant. Many forms of drug - resistant epilepsy occur in children. In the control mother of epilepsy patients, we did not find any cases that show resistance to drugs or drugs. More than 90% of these patients had their epilepsy controlled with one drug and about 10% with two drugs

In the patients that we have monitored, it has been found that 17% have stopped taking their medications by themselves for more than two years without consulting any doctor and have been free of any attacks in these two years.

 

The main drugs used by our patients include the following:

1Nearly 47% of patients have used carbamazepine tabs  to treat their disease. The medicinal dose is between 400 and 800 mg daily in two or three times tablet

2.Levetiracetam tabs have used % 17 by the patient’s have used. Of course, it is a new drug and the doses used by these patients range from 500 mg  to 1 gram per day in two doses.

3.Valpuric acid tablets, almost 14% of patients have been treated with this medicine . The therapeutic doses of this drug are reported to be 500 to 750 mg in two doses.

4.About 7% of patients were treated with  Apixaban tablets.

5.Also, 7% of patients used two drugs.

 

Figure 2

In our investigations, we did not find any case that showed resistance to a specific drug treatment.

Also, we did not receive any reports of allergy or intolerance to antiepileptic drugs in these patients

 

Some strong studies  about

In adults, there are two studies in which seizure - free patients were randomized They were divided into those who decided to continue the treatment.

A randomized controlled study of 1,013 patients who had been seizure -free for at least two years found that 41% relapsed two years after discontinuation, compared with 22 % in the group that  shows continued treatment.

A Norwegian randomized study included 160 patients who were treated with monotherapy for at least two years without seizures . They were randomly divided into stopping  79 people  or continuing treatment 81 people . After 12 months 15  percent of those in the discontinuation group and 7 percent of those in the continuation group experienced a seizure recurrence .

In an open-label follow-up study , 89 % of patients randomized to continue treatment chose to discontinue the drug . After 41 months, seizures had recurred in 27 percent of those who stopped  treatment.

A meta - analysis based on 25 observational studies reported seizure recurrence in 25% after one year and in 29% two years after discontinuation.

An American guideline based on 17 observational studies resulted in a similar post - discontinuation rate of 31.2 % for children and 39.4 % for adults

 

Do the seizures come back?

This is a big question. And this possibility is often what makes the decision whether to discontinue the Or not .

It is usually not an option for people with a type of epilepsy that rarely goes away , such as juvenile myoclonic epilepsy . When you stop taking the drug , relapse is almost certain .

But approximately three quarters of people with epilepsy have a form that is far less predictable .

 

Seizures are less likely to return if  the patients  have the following :

 

• Free attacks for at least 2 to 5 years.
• Have only one type of seizure. 
• E.E.G for at least 1 year is normal.

Seizures are more likely to return if  the patients  have the following:
• Chronic epilepsy
• Multiple or mixed epilepsy
• Failure to control seizures despite the use of antiepileptic drugs
• Attempts to stop in the past were unsuccessful
• Intelligence score less than 70 
• Abnormal  E.E.G since last year. 
• Worsening of  E.E.G in the absence of medication

 

 

Final results:

According to our case, after 40 years, despite the use of medication, Grandmal's epilepsy attacks returned even more severe than before. We are convinced that discontinuation of antiepileptic drugs is not practical for trauma patients. We also concluded that

•  In epileptic patients with direct trauma, we should not negotiate at all.
•  For those who want to test stopping the drug, use the low tappering method and continue this for a  3 months.
•  Do not change the drugs that patients use, even their pharmaceutical companies.
•  Patients who have psychological problems for any reason, in cooperation with the teams of our psychologist colleagues, let's work together on their treatments.
•  In those whose cause of trauma, such as tumors or similar cases, has been eliminated, we can consider the continuation of treatment with our colleagues and examine the issue of reducing or stopping the medication.
•  We still haven't been able to academically assess the relationship between chronic  Covid  epileptic attacks, that's why we keep this part of the work open for now to complete our information.

 

References

Medically Reviewed by Christopher Melinosky, MD on August 25, 2021

Written by Julie Canter Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy . Correspondence to:Professor LM Specchio, Epilepsy Center, Neurological Clinic I, University of Bari, Department of Neurological and Psychiatric Sciences, Policlinico Hospital, Piazza G Cesare, 70124 – Bari, Italy;epilepsy@cimedoc.uniba.it

Stopping Antiepileptic Drugs: When and Why?

John D. Hixson MD

Discontinuation of antiepileptic drugs in seizure-free patients – when and how?

Morten I. Lossius, Kristin Å. Alfstad, Kari M. Aaberg, Karl Otto Nakken About the authors

Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000; 342:314-9. 10.1056/NEJM200002033420503 [PubMed] [CrossRef] [Google Scholar]

Baker GA, Jacoby A, Buck D, Stalgis C, Monnet D. Quality of life of people with epilepsy: a European study. Epilepsia 1997; 38:353-62. 10.1111/j.1528-1157.1997.tb01128.x [PubMed] [CrossRef] [Google Scholar]

Carbone LD, Johnson KC, Robbins J, Larson JC, Curb JD, Watson K, et al. Antiepileptic drug use, falls, fractures, and BMD in postmenopausal women: findings from the women’s health initiative (WHI). J Bone Miner Res 2010;25:873-81. 10.1359/jbmr.091027 [PMC free article] [PubMed] [CrossRef] [Google Scholar]

Tomson T, Battino D, Bromley R, Kochen S, Meador K, Pennell P, et al. Management of epilepsy in pregnancy: a report from the International League Against Epilepsy Task Force on Women and Pregnancy. Epileptic Disord 2019; 21:497-517. 10.1684/epd.2019.1105 [PubMed] [CrossRef] [Google Scholar]

Lamberink HJ, Otte WM, Geerts AT, Pavlovic M, Ramos-Bizana J, Marson AG, et al. Individualized prediction model of seizure recurrence and long-term outcomes after withdrawal of antiepileptic drugs in seizure-free patients: a systematic review and individual participant data meta-analysis. Lancet Neurol 2017; 16:523-31. 10.1016/S1474-4422(17)30114-X [PubMed] [CrossRef] [Google Scholar]

Medical Research Council Antiepileptic Drug Withdrawal Study Group . Randomized study of antiepileptic drug withdrawal in patients in remission. Lancet 1991; 337:1175-80. [PubMed] [Google Scholar]

Berg AT, Shinnar S. Relapse following discontinuation of antiepileptic drugs: a meta-analysis. Neurology 1994; 44:601-8. 10.1212/WNL.44.4.601 [PubMed] [CrossRef] [Google Scholar]

Schmidt D, Sillanpää M. Stopping epilepsy treatment in seizure remission: Good or bad or both? Seizure 2017; 44:157-61. 10.1016/j.seizure.2016.09.003 [PubMed] [CrossRef] [Google Scholar]

Cvetkovska E, Babunovska M, Kuzmanovski I, Boskovski B, Sazdova-Burneska S, Aleksovski V, et al. Patients’ attitude toward AED withdrawal: A survey among individuals who had been seizure-free for over 2?years. Epilepsy Behav 2020;104 Pt A:106881. 10.1016/j.yebeh.2019.106881 [PubMed] [CrossRef] [Google Scholar]

Beghi E, Giussani G, Grosso S, Iudice A, La Neve A, Pisani F, et al. Withdrawal of antiepileptic drugs: guidelines of the Italian League Against Epilepsy. Epilepsia 2013;54 Suppl 7:2-12. 10.1111/epi.12305 [PubMed] [CrossRef] [Google Scholar]

Schmidt D, Löscher W. Uncontrolled epilepsy following discontinuation of antiepileptic drugs in seizure-free patients: a review of current clinical experience. Acta Neurol Scand 2005; 111:291-300. [PubMed] [CrossRef] [Google Scholar]

Assessing fitness to drive for commercial and private vehicle drivers. 2016 Medical standards for licensing and clinical management guidelines. Sydney: Ausroads. p. 93. https://austroads.com.au/publications/assessing-fitness-to-drive/ap-g56 [cited 2021 Mar 1]

Schmidt D, Baumgartner C, Löscher W. Seizure recurrence after planned discontinuation of antiepileptic drugs in seizure-free patients after epilepsy surgery: a review of current clinical experience. Epilepsia 2004; 45:179-86. 10.1111/j.0013-9580.2004.37803.x [PubMed] [CrossRef] [Google Scholar].