I'm away visiting
with family and friends
I'll post some more
when my holiday ends.
Until then
Happy New Year and
here's to a great
2008.
OK, so the rhyming scheme isn't consistent. In my defense, all my blood is being diverted away from my brain and towards my stomach.
I have some exciting posts planned for the New Year, so please stay tuned. And, as always, feel free to post your questions/comments below.
All the best,
Kirk.
Friday, December 28, 2007
Friday, December 21, 2007
See An Epileptologist
I have heard this story too many times: someone has seizures- they go to a family physician- they are misdiagnosed or placed on the wrong drug- they have uncontrolled seizures for years- they don't realize they might be able to optimize their diagnosis and treatment.
The Mechanic Allegory
You get in your car one day to head to work. Upon shifting into reverse you hear a horrific *CLANK*. Being the clever person you are, you have figured out that your car's transmission has just died. So, you need to get your car fixed. You have 3 options: 1) Take your car to the general mechanic around the corner. He doesn't know much about transmissions, but he might get it fixed without too much trouble. 2) Take your car to the "drive-train" specialists down the street. She is a step-up from the general mechanic in terms of expertise, but the drive-train involves many different pieces and you're not sure how much she knows about the transmission itself. 3) Take your car to the transmission specialist across town. They know the most about transmissions and are likely to do the best job.
All other things being equal, who do you go see?
Correct- you go see an epileptologist! (my attempt at a joke)
What is an Epileptologist?
Generally speaking, an epileptologist is someone who specializes in the study of epilepsy. For the purposes of this post, we'll say that it's a neurologist that specializes in epilepsy diagnosis and treatment.
Where are all the Epileptologists?
Unfortunately, my knowledge is fairly limited to the US and Canada. If anyone has links to a list of epileptologists/epilepsy clinics in other countries, please post them below. Here are a few links to places you can find epileptologists.
Canada
United Kingdom
United States*
*The U.S.A. has comprehensive epilepsy care clinics. These are "1-stop" centers that have their own epileptologists, neurosurgeons, nurses, EEG technicians, brain imaging technicians, neuropsychologists/ psychiatrists, dietitians with all their corresponding equipment. Canada is currently exploring the idea of developing epilepsy centres. The closest thing Canada currently has to comprehensive epilepsy centres are The Hospital for Sick Children (Toronto, ON), Toronto Western Hospital (Toronto, ON) and London Health Sciences Centre (London, ON).
Take Home Message
If you, or someone you know, has uncontrolled epilepsy and have not seen an epileptologist- then try to see one.
Merry Christmas everyone!
Please feel free to comment, post questions or leave me some ideas for future posts.
Kirk.
The Mechanic Allegory
You get in your car one day to head to work. Upon shifting into reverse you hear a horrific *CLANK*. Being the clever person you are, you have figured out that your car's transmission has just died. So, you need to get your car fixed. You have 3 options: 1) Take your car to the general mechanic around the corner. He doesn't know much about transmissions, but he might get it fixed without too much trouble. 2) Take your car to the "drive-train" specialists down the street. She is a step-up from the general mechanic in terms of expertise, but the drive-train involves many different pieces and you're not sure how much she knows about the transmission itself. 3) Take your car to the transmission specialist across town. They know the most about transmissions and are likely to do the best job.
All other things being equal, who do you go see?
Correct- you go see an epileptologist! (my attempt at a joke)
What is an Epileptologist?
Generally speaking, an epileptologist is someone who specializes in the study of epilepsy. For the purposes of this post, we'll say that it's a neurologist that specializes in epilepsy diagnosis and treatment.
Where are all the Epileptologists?
Unfortunately, my knowledge is fairly limited to the US and Canada. If anyone has links to a list of epileptologists/epilepsy clinics in other countries, please post them below. Here are a few links to places you can find epileptologists.
Canada
United Kingdom
United States*
*The U.S.A. has comprehensive epilepsy care clinics. These are "1-stop" centers that have their own epileptologists, neurosurgeons, nurses, EEG technicians, brain imaging technicians, neuropsychologists/ psychiatrists, dietitians with all their corresponding equipment. Canada is currently exploring the idea of developing epilepsy centres. The closest thing Canada currently has to comprehensive epilepsy centres are The Hospital for Sick Children (Toronto, ON), Toronto Western Hospital (Toronto, ON) and London Health Sciences Centre (London, ON).
Take Home Message
If you, or someone you know, has uncontrolled epilepsy and have not seen an epileptologist- then try to see one.
Merry Christmas everyone!
Please feel free to comment, post questions or leave me some ideas for future posts.
Kirk.
Tuesday, December 18, 2007
National Walk for Epilepsy
The 2008 National Walk for Epilepsy
Mark your calendars- on March 29th, 2008 the Epilepsy Foundation is hosting its 2nd Annual National Walk for Epilepsy. The Walk takes place in Washington, D.C. during a very beautiful time of year, cherry blossom season. Now is a great time to sign up and start raising funds, both to get there yourself and/or to raise money for the Foundation. This is the American Walk for Epilepsy -- I'll discuss below plans for Canada's First National Walk for Epilepsy.
Long Overdue- But Better Late Than Never
Finally, a National event to raise awareness and money for epilepsy. Epilepsy is probably one of the oldest known disorders. Pythagoras and Socrates were said to have suffered from seizures. Why is it that only now (2500 years later) we are seeing National Walks and other great fund-raising initiatives for epilepsy? Better late than never though, right? Right.
Speaking of "Better Late Than Never"
My wife and I attended the 1st Annual National Walk for Epilepsy last year and it was wonderful. This might be old news to some, but I thought I'd post on it for those of you who don't know about the Walk or are interested in some details. It took place on the National Mall, Washington D.C. on March 31, 2007. It consisted of walking 5kms (why would an American foundation advertise a 5 kilometer walk? I guess a "3.10685 mile Walk" doesn't roll of the tongue very well) down the National Mall and by all of the great museums and heritage buildings.
Before-hand, I presented my research at the National Institutes of Health's "Curing Epilepsy 2007" conference in Bethesda, Maryland. This conference consisted of talks by some of the world's most eminent epilepsy researchers. Naturally, the conference promoted the Walk and many of the conference attendees stuck around for an extra day to take part in the Walk.
I was excited about the Walk. My nephew had been recently diagnosed with epilepsy and my wife and I saw this as a great chance to support him. The Walk began Saturday morning, bright and early. It was a gorgeous Spring day. My wife and I did a few cartwheels outside the Canadian Embassy on our way to the National Mall. The energy was a mixture of sadness and hope. Many people had team shirts made up for the Walk. Some shirts told of how a loved one died of SUDEP (Sudden, Unexplained Death in Epilepsy). Others had shirts telling everyone what State they were representing.
Some people did the 5km Walk in a wheel chair. Some ran the 5km. Most simply walked the Walk (pardon the pun). It was very exciting being surrounded by 3000 other people with a common goal/desire: to raise money and awareness for epilepsy. In the end, the Walk was a success. There were representatives from every State (I suspect that we were the only "Canucks" present) and they raised a little over $1,000,000 for the Epilepsy Foundation. That money will go towards supporting those with epilepsy, promoting epilepsy awareness and funding some epilepsy research.
Why a Walk?
A National Walk is a great way to raise both money and awareness for an issue. Most of the 3000 walkers solicited support from several friends and family members. The word really gets out there, causing a ripple effect that brings the topic of epilepsy into the collective conscious of a Nation.
A Canadian Walk for Epilepsy
Canada is currently in the early stages of organizing a National Walk for Epilepsy. The goal is have the Walk in mid- to late-2008. I'll definitely keep everyone updated as the plans progress.
Onward and upward!
Kirk.
Mark your calendars- on March 29th, 2008 the Epilepsy Foundation is hosting its 2nd Annual National Walk for Epilepsy. The Walk takes place in Washington, D.C. during a very beautiful time of year, cherry blossom season. Now is a great time to sign up and start raising funds, both to get there yourself and/or to raise money for the Foundation. This is the American Walk for Epilepsy -- I'll discuss below plans for Canada's First National Walk for Epilepsy.
Long Overdue- But Better Late Than Never
Finally, a National event to raise awareness and money for epilepsy. Epilepsy is probably one of the oldest known disorders. Pythagoras and Socrates were said to have suffered from seizures. Why is it that only now (2500 years later) we are seeing National Walks and other great fund-raising initiatives for epilepsy? Better late than never though, right? Right.
Speaking of "Better Late Than Never"
My wife and I attended the 1st Annual National Walk for Epilepsy last year and it was wonderful. This might be old news to some, but I thought I'd post on it for those of you who don't know about the Walk or are interested in some details. It took place on the National Mall, Washington D.C. on March 31, 2007. It consisted of walking 5kms (why would an American foundation advertise a 5 kilometer walk? I guess a "3.10685 mile Walk" doesn't roll of the tongue very well) down the National Mall and by all of the great museums and heritage buildings.
Before-hand, I presented my research at the National Institutes of Health's "Curing Epilepsy 2007" conference in Bethesda, Maryland. This conference consisted of talks by some of the world's most eminent epilepsy researchers. Naturally, the conference promoted the Walk and many of the conference attendees stuck around for an extra day to take part in the Walk.
I was excited about the Walk. My nephew had been recently diagnosed with epilepsy and my wife and I saw this as a great chance to support him. The Walk began Saturday morning, bright and early. It was a gorgeous Spring day. My wife and I did a few cartwheels outside the Canadian Embassy on our way to the National Mall. The energy was a mixture of sadness and hope. Many people had team shirts made up for the Walk. Some shirts told of how a loved one died of SUDEP (Sudden, Unexplained Death in Epilepsy). Others had shirts telling everyone what State they were representing.
Some people did the 5km Walk in a wheel chair. Some ran the 5km. Most simply walked the Walk (pardon the pun). It was very exciting being surrounded by 3000 other people with a common goal/desire: to raise money and awareness for epilepsy. In the end, the Walk was a success. There were representatives from every State (I suspect that we were the only "Canucks" present) and they raised a little over $1,000,000 for the Epilepsy Foundation. That money will go towards supporting those with epilepsy, promoting epilepsy awareness and funding some epilepsy research.
Why a Walk?
A National Walk is a great way to raise both money and awareness for an issue. Most of the 3000 walkers solicited support from several friends and family members. The word really gets out there, causing a ripple effect that brings the topic of epilepsy into the collective conscious of a Nation.
A Canadian Walk for Epilepsy
Canada is currently in the early stages of organizing a National Walk for Epilepsy. The goal is have the Walk in mid- to late-2008. I'll definitely keep everyone updated as the plans progress.
Onward and upward!
Kirk.
Friday, December 14, 2007
The Ketogenic Diet and Friends
It's Friday and I want to have some fun- so I'm going to post about the ketogenic diet. I'll introduce the concept of dietary treatment of epilepsy now. I'll discuss how these diets might be working in a later post.
What is the Ketogenic Diet?
The ketogenic diet is a high fat, low carbohydrate and adequate-protein diet used to treat drug-resistant seizures. The most commonly used "classic" ketogenic diet has a 4:1 ratio. This means that there are 4 parts of fat to every 1 part of combined carbohydrate and protein (by weight). Translation: about 90% of your caloric intake is in the form of fat. Normally our body uses carbohydrate (sugars) as the main energy source. When dietary carbohydrates are severely limited (ie, almost no potatoes, rice, noodles, fruit, or candy) the body goes looking elsewhere for energy. Our bodies have a "backup system" that uses fat for energy. The KD provides a lot of fat for this back-up system to use.
Who Goes on the Ketogenic Diet?
Approximately 20-30% of people with epilepsy will not see a significant seizure reduction with the anticonvulsant drugs. These people are said to have "drug resistant", "medically refractory" or "intractable" seizures. One of the alternative treatment options for these individuals is the ketogenic diet. Aside from neurosurgery, the KD is one of the only alternative treatments that could "cure" epilepsy. I use quotes to qualify the word "cure". There's a small percentage of patients that will achieve seizure freedom on the KD and when taken off the diet (after a few years), their seizures never come back. It's hard to say whether the diet has cured their epilepsy or whether they simply out-grew their epilepsy while on the diet.
Is the Ketogenic Diet "Natural"?
The short answer is a definite, resounding NO! There is nothing natural about having fat represent 90% of your daily caloric intake. That said, there is nothing natural about the drugs either. My opinion is to eliminate "naturalness" as a factor when making a therapeutic decision for epilepsy treatment. Rather, weigh the pros-and-cons of "severity of treatment" and "severity of seizures" with the "possible benefit of the treatment".
Strengths of the Ketogenic Diet
---Anticonvulsant Effect---
The main strength of the ketogenic diet is that it is very good at suppressing seizures. Clinical data suggest that about 60% of patients will see a >50% reduction in seizures with 10-15% of this group seeing a >90% reduction in their seizures. About 40% will see a less than 50% reduction in their seizures. This is remarkable given that these are individuals that have already failed to see a significant improvement on two or more anticonvulsant drugs.
---Cognitive and Behavioral Effect---
There is a growing body of evidence (although most of it remains anecdotal) that the KD is associated with beneficial cognitive and behavioral effects. There are anecdotes of parents putting their kids on the KD and seeing no change in seizure frequency. However, they saw such good changes in mood and cognition that they kept their child on the diet anyway.
Problems of the Ketogenic Diet
The KD is not without problems. Below are some of the most common issues/questions regarding the diet.
---Will I Gain Weight on the Ketogenic Diet?---
Many people think you'll get fat on this diet, but the opposite is true- you'll actually lose some weight as the diet turbo-charges the fat burning machinery of the body. Carbohydrates and protein, nutrients limited by the KD, are both important in growth and maturation.
---Side Effects of the Ketogenic Diet---
Decreased bone density, stunted growth, vitamin and mineral deficiencies (most KD programs will require individuals to take vitamin and mineral supplements), cardio-vascular disease with prolonged use, kidney stones (1-2% risk).
Risk of these "adverse events" need to be weighed with the severity and the degree of drug-resistance of the seizures.
Adherence
Perhaps the largest issue facing the use of the KD is adherence. A large proportion of those that start the diet tend to quit due to the fact that it's too restrictive and rigorous. For example, you need to weigh all of your food to the 100th of a gram and know all of the food's nutritional content. The diet works in both kids and adults. Many neurologists say the diet works less well in adults, but this is simply because adults are more likely to say "forget this nonsense, I'm going to enjoy a chocolate bar" whereas children can have their diets imposed on them by their parents (it's an autonomy issue, really).
Autonomy on the Ketogenic Diet
The autonomy (or freedom) of an individual on the KD is significantly affected by the dietary limits imposed by the KD. Kids can't trade lunches or enjoy a fresh-baked chocolate chip cookie. This really cramps the style of a grade-schooler. Sometimes locks need to be put on the fridge/cupboards to prevent the sneaking of a sugary snack. This is a significant factor to consider when deciding whether or not to try the ketogenic diet.
Other Diet Options
The new, exciting news is that the Atkins diet (www.atkinsforseizures.com) and the low-glycemic index diet (LGID for short) also appear to work like the ketogenic diet. They are also much less restrictive in terms of what you can/cannot eat. The tough part is finding a hospital with a neurologist/dietician that work with these diets for the treatment of drug-resistant epilepsy. Certainly, these diets may be much better tolerated by adults as they require less "cramping" of your culinary lifestyle. They also appear to be associated with fewer side-effects- although more research is needed before these diets become as common-place as the KD.
So there's a brief introduction to the ketogenic diet and its friends.
As always, Please feel free to post any comments/questions you may have.
Kirk.
What is the Ketogenic Diet?
The ketogenic diet is a high fat, low carbohydrate and adequate-protein diet used to treat drug-resistant seizures. The most commonly used "classic" ketogenic diet has a 4:1 ratio. This means that there are 4 parts of fat to every 1 part of combined carbohydrate and protein (by weight). Translation: about 90% of your caloric intake is in the form of fat. Normally our body uses carbohydrate (sugars) as the main energy source. When dietary carbohydrates are severely limited (ie, almost no potatoes, rice, noodles, fruit, or candy) the body goes looking elsewhere for energy. Our bodies have a "backup system" that uses fat for energy. The KD provides a lot of fat for this back-up system to use.
Who Goes on the Ketogenic Diet?
Approximately 20-30% of people with epilepsy will not see a significant seizure reduction with the anticonvulsant drugs. These people are said to have "drug resistant", "medically refractory" or "intractable" seizures. One of the alternative treatment options for these individuals is the ketogenic diet. Aside from neurosurgery, the KD is one of the only alternative treatments that could "cure" epilepsy. I use quotes to qualify the word "cure". There's a small percentage of patients that will achieve seizure freedom on the KD and when taken off the diet (after a few years), their seizures never come back. It's hard to say whether the diet has cured their epilepsy or whether they simply out-grew their epilepsy while on the diet.
Is the Ketogenic Diet "Natural"?
The short answer is a definite, resounding NO! There is nothing natural about having fat represent 90% of your daily caloric intake. That said, there is nothing natural about the drugs either. My opinion is to eliminate "naturalness" as a factor when making a therapeutic decision for epilepsy treatment. Rather, weigh the pros-and-cons of "severity of treatment" and "severity of seizures" with the "possible benefit of the treatment".
Strengths of the Ketogenic Diet
---Anticonvulsant Effect---
The main strength of the ketogenic diet is that it is very good at suppressing seizures. Clinical data suggest that about 60% of patients will see a >50% reduction in seizures with 10-15% of this group seeing a >90% reduction in their seizures. About 40% will see a less than 50% reduction in their seizures. This is remarkable given that these are individuals that have already failed to see a significant improvement on two or more anticonvulsant drugs.
---Cognitive and Behavioral Effect---
There is a growing body of evidence (although most of it remains anecdotal) that the KD is associated with beneficial cognitive and behavioral effects. There are anecdotes of parents putting their kids on the KD and seeing no change in seizure frequency. However, they saw such good changes in mood and cognition that they kept their child on the diet anyway.
Problems of the Ketogenic Diet
The KD is not without problems. Below are some of the most common issues/questions regarding the diet.
---Will I Gain Weight on the Ketogenic Diet?---
Many people think you'll get fat on this diet, but the opposite is true- you'll actually lose some weight as the diet turbo-charges the fat burning machinery of the body. Carbohydrates and protein, nutrients limited by the KD, are both important in growth and maturation.
---Side Effects of the Ketogenic Diet---
Decreased bone density, stunted growth, vitamin and mineral deficiencies (most KD programs will require individuals to take vitamin and mineral supplements), cardio-vascular disease with prolonged use, kidney stones (1-2% risk).
Risk of these "adverse events" need to be weighed with the severity and the degree of drug-resistance of the seizures.
Adherence
Perhaps the largest issue facing the use of the KD is adherence. A large proportion of those that start the diet tend to quit due to the fact that it's too restrictive and rigorous. For example, you need to weigh all of your food to the 100th of a gram and know all of the food's nutritional content. The diet works in both kids and adults. Many neurologists say the diet works less well in adults, but this is simply because adults are more likely to say "forget this nonsense, I'm going to enjoy a chocolate bar" whereas children can have their diets imposed on them by their parents (it's an autonomy issue, really).
Autonomy on the Ketogenic Diet
The autonomy (or freedom) of an individual on the KD is significantly affected by the dietary limits imposed by the KD. Kids can't trade lunches or enjoy a fresh-baked chocolate chip cookie. This really cramps the style of a grade-schooler. Sometimes locks need to be put on the fridge/cupboards to prevent the sneaking of a sugary snack. This is a significant factor to consider when deciding whether or not to try the ketogenic diet.
Other Diet Options
The new, exciting news is that the Atkins diet (www.atkinsforseizures.com) and the low-glycemic index diet (LGID for short) also appear to work like the ketogenic diet. They are also much less restrictive in terms of what you can/cannot eat. The tough part is finding a hospital with a neurologist/dietician that work with these diets for the treatment of drug-resistant epilepsy. Certainly, these diets may be much better tolerated by adults as they require less "cramping" of your culinary lifestyle. They also appear to be associated with fewer side-effects- although more research is needed before these diets become as common-place as the KD.
So there's a brief introduction to the ketogenic diet and its friends.
As always, Please feel free to post any comments/questions you may have.
Kirk.
Wednesday, December 12, 2007
The Drugs: Wherefore and Whence?
Anticonvulsant Drugs, Antiseizure Drugs or Antiepileptic Drugs?
I am seldom picky over words, but I really dislike the term "antiepileptic drug". It sounds like a pill you take if you don't like people with epilepsy. Some rogue, pill-popping gang wandering the streets with a score to settle against those who have epilepsy. Whoever coined this term obviously didn't eat their Wheaties.
Two more acceptable terms are "antiseizure drugs" and "anticonvulsant drugs". Strictly speaking, a seizure is an electrographic event. It is the disruption of brain activity that we can measure using an EEG (see "What is a Seizure" below). A seizure may or may not be associated with a convulsion. A convulsion is the movement/behavior caused by a seizure. For example, tonic-clonic* (formerly called grand mal) seizures cause tonic-clonic movements therefore it is a convulsive seizure. Other seizures, however, do not cause convulsions. For example, simple partial seizures that do not affect motor areas of the brain will not cause any movement- therefore they are non-convulsive seizures. I tend to use the terms "anticonvulsant drugs" and "antiseizure drugs" interchangeably.
*Tonus is continuous contraction of the muscles, causing the limbs to straighten and become stiff. Clonus is the repeated contraction and relaxation of the muscles which results in a jerking movement.
The Drugs.
Upon being diagnosed with epilepsy, the first course of treatment is generally the drugs.
Until the mid 1990s, the "traditional" anticonvulsants were the most commonly prescribed (drugs listed by generic name with trade name in parentheses). These include phenobarbital (Luminal®), primidone (Mysoline®), phenytoin (Dilantin®), carbamazepine (Tegretol®), ethosuximide (Zarontin®), clonazepam (Rivotril®) and valproate (Depakene®). These "first-line" anticonvulsant drugs are only effective in 60-70% of patients. They may also be associated with severe side effects.
In the past decade, a number of new drugs have been introduced to the market. These include felbamate (Felbatol®), fosphenytoin sodium (Cerebyx®), oxcarbazepine (Trileptal®), gabapentin (Neurontin®), lamotrigine (Lamictal®), zonisamide (Zonegran®), levetiracetam (Keppra®), tiagabine (Gabitril®), pregabalin (Lyrica®) and topiramate (Topamax®). Although these newer drugs have fewer side effects, they do not appear to be more effective at stopping seizures than the traditional drugs- meaning 20-30% of patients will not gain adequate seizure control on these meds.
How the Drugs Work.
The new anticonvulsant drugs may not be more effective than the old anticonvulsant drugs because they tend to work in very similar ways. Anticonvulsant drugs generally work to decrease excitation or increase inhibition in the brain. This is usually accomplished by one of three mechanisms: enhancing GABA activity, decreasing sodium channel activity, or decreasing T-type calcium channel activity.
GABA Drugs.
GABA (also know by the less cuddly name: gamma-aminobutyric acid) is the major inhibitory chemical in the brain. It works by slamming on the proverbial brakes (see car analogy under "What is a Seizure" below). The GABA drugs elevate levels of GABA in the brain. Slamming on the brakes will make the brain less excitable and less prone to seizures. It will also make it harder to remember things and stay alert/energetic. This is because these drugs raise GABA levels all over the brain, and not just in the area(s) that cause the seizure.
A number of the anticonvulsants enhance the activity of GABA, often indirectly. Examples of such drugs are: phenobarbital (Luminal®), primidone (Mysoline®), topiramate (Topamax®), diazepam (Valium®) and tiagabine (Gabitril®).
Sodium Channel Blockers.
Sodium channels (specifically, voltage-gated sodium channels) are responsible for the firing of neurons in the brain. Think of a neuron as a water hose. The hose is full of little gates, however, that prevent the water from flowing through it. When the gates "sense" that water is coming, they open and allow the water to flow through. This is a rough analogy of how the voltage gated sodium channels work- only instead of water they allow the passage of positively charged ions (like sodium) into the cell which allows the signal to carry on.
Drugs that work on sodium channels in the brain tend to delay these channels, causing neurons to fire a tiny bit slower than normal. Examples of voltage-gated sodium channel drugs are phenytoin (Dilantin®), carbamazepine (Tegretol®), felbamate (Felbatol®), lamotrigine (Lamictal®), oxcarbazepine (Trileptal®), pregabalin (Lyrica®), topiramate (Topamax®) and zonisamide (Zonegran®).
Calcium Channel Blockers.
T-type calcium channels are thought to cause rhythmic neuronal firing associated with absence seizures. Similar to sodium channels, calcium channels open and allow positively charged ions to enter the cell -- only this time it's calcium and not sodium. Calcium channel blockers tend to be most effective in treating absence seizures. Examples of drugs acting on calcium channels are ethosuximide (Zarontin®), felbamate (Felbatol®), lamotrigine (Lamictal®), topiramate (Topamax®) and zonisamide (Zonegran®).
Drugs for the Treatment of Status Epilepticus.
Status epilepticus is a seizure that does not end on its own. Generally, someone is said to be in status if their seizure lasts longer than 5 minutes. This is when it's important to get to a hospital/call 911 as special drugs will be required to stop these seizures (see "Seizure First Aid" below). These include diazepam (Valium®), lorazepam (Ativan®) and sometimes general anesthetics such as propofol (Diprivan®).
Other Treatments for Epilepsy
This post is long enough. Later, I will cover non-drug treatments such as the ketogenic diet, vagal nerve stimulator and neurosurgery.
Onwards and upwards!
Kirk.
References:
Browne TR & Holmes GL. 2001. Epilepsy – Primary Care. New England Journal of Medicine. 344, 1145-1151.
Burnham WM. 1998. Antiseizure drugs. In: Principles of Medical Pharmacology. New York: 250-277.
Catterall WA. 1987. Common modes of drug action on Na+ channels: local anesthetics, antiarrhythmics and anticonvulsants. Trends in Pharmacological Science. 8, 57-65.
LaRoche SM & Helmers SL. 2004. The new antiepileptic drugs. Journal of the American Medical Association. 291, 605-614.
I am seldom picky over words, but I really dislike the term "antiepileptic drug". It sounds like a pill you take if you don't like people with epilepsy. Some rogue, pill-popping gang wandering the streets with a score to settle against those who have epilepsy. Whoever coined this term obviously didn't eat their Wheaties.
Two more acceptable terms are "antiseizure drugs" and "anticonvulsant drugs". Strictly speaking, a seizure is an electrographic event. It is the disruption of brain activity that we can measure using an EEG (see "What is a Seizure" below). A seizure may or may not be associated with a convulsion. A convulsion is the movement/behavior caused by a seizure. For example, tonic-clonic* (formerly called grand mal) seizures cause tonic-clonic movements therefore it is a convulsive seizure. Other seizures, however, do not cause convulsions. For example, simple partial seizures that do not affect motor areas of the brain will not cause any movement- therefore they are non-convulsive seizures. I tend to use the terms "anticonvulsant drugs" and "antiseizure drugs" interchangeably.
*Tonus is continuous contraction of the muscles, causing the limbs to straighten and become stiff. Clonus is the repeated contraction and relaxation of the muscles which results in a jerking movement.
The Drugs.
Upon being diagnosed with epilepsy, the first course of treatment is generally the drugs.
Until the mid 1990s, the "traditional" anticonvulsants were the most commonly prescribed (drugs listed by generic name with trade name in parentheses). These include phenobarbital (Luminal®), primidone (Mysoline®), phenytoin (Dilantin®), carbamazepine (Tegretol®), ethosuximide (Zarontin®), clonazepam (Rivotril®) and valproate (Depakene®). These "first-line" anticonvulsant drugs are only effective in 60-70% of patients. They may also be associated with severe side effects.
In the past decade, a number of new drugs have been introduced to the market. These include felbamate (Felbatol®), fosphenytoin sodium (Cerebyx®), oxcarbazepine (Trileptal®), gabapentin (Neurontin®), lamotrigine (Lamictal®), zonisamide (Zonegran®), levetiracetam (Keppra®), tiagabine (Gabitril®), pregabalin (Lyrica®) and topiramate (Topamax®). Although these newer drugs have fewer side effects, they do not appear to be more effective at stopping seizures than the traditional drugs- meaning 20-30% of patients will not gain adequate seizure control on these meds.
How the Drugs Work.
The new anticonvulsant drugs may not be more effective than the old anticonvulsant drugs because they tend to work in very similar ways. Anticonvulsant drugs generally work to decrease excitation or increase inhibition in the brain. This is usually accomplished by one of three mechanisms: enhancing GABA activity, decreasing sodium channel activity, or decreasing T-type calcium channel activity.
GABA Drugs.
GABA (also know by the less cuddly name: gamma-aminobutyric acid) is the major inhibitory chemical in the brain. It works by slamming on the proverbial brakes (see car analogy under "What is a Seizure" below). The GABA drugs elevate levels of GABA in the brain. Slamming on the brakes will make the brain less excitable and less prone to seizures. It will also make it harder to remember things and stay alert/energetic. This is because these drugs raise GABA levels all over the brain, and not just in the area(s) that cause the seizure.
A number of the anticonvulsants enhance the activity of GABA, often indirectly. Examples of such drugs are: phenobarbital (Luminal®), primidone (Mysoline®), topiramate (Topamax®), diazepam (Valium®) and tiagabine (Gabitril®).
Sodium Channel Blockers.
Sodium channels (specifically, voltage-gated sodium channels) are responsible for the firing of neurons in the brain. Think of a neuron as a water hose. The hose is full of little gates, however, that prevent the water from flowing through it. When the gates "sense" that water is coming, they open and allow the water to flow through. This is a rough analogy of how the voltage gated sodium channels work- only instead of water they allow the passage of positively charged ions (like sodium) into the cell which allows the signal to carry on.
Drugs that work on sodium channels in the brain tend to delay these channels, causing neurons to fire a tiny bit slower than normal. Examples of voltage-gated sodium channel drugs are phenytoin (Dilantin®), carbamazepine (Tegretol®), felbamate (Felbatol®), lamotrigine (Lamictal®), oxcarbazepine (Trileptal®), pregabalin (Lyrica®), topiramate (Topamax®) and zonisamide (Zonegran®).
Calcium Channel Blockers.
T-type calcium channels are thought to cause rhythmic neuronal firing associated with absence seizures. Similar to sodium channels, calcium channels open and allow positively charged ions to enter the cell -- only this time it's calcium and not sodium. Calcium channel blockers tend to be most effective in treating absence seizures. Examples of drugs acting on calcium channels are ethosuximide (Zarontin®), felbamate (Felbatol®), lamotrigine (Lamictal®), topiramate (Topamax®) and zonisamide (Zonegran®).
Drugs for the Treatment of Status Epilepticus.
Status epilepticus is a seizure that does not end on its own. Generally, someone is said to be in status if their seizure lasts longer than 5 minutes. This is when it's important to get to a hospital/call 911 as special drugs will be required to stop these seizures (see "Seizure First Aid" below). These include diazepam (Valium®), lorazepam (Ativan®) and sometimes general anesthetics such as propofol (Diprivan®).
Other Treatments for Epilepsy
This post is long enough. Later, I will cover non-drug treatments such as the ketogenic diet, vagal nerve stimulator and neurosurgery.
Onwards and upwards!
Kirk.
References:
Browne TR & Holmes GL. 2001. Epilepsy – Primary Care. New England Journal of Medicine. 344, 1145-1151.
Burnham WM. 1998. Antiseizure drugs. In: Principles of Medical Pharmacology. New York: 250-277.
Catterall WA. 1987. Common modes of drug action on Na+ channels: local anesthetics, antiarrhythmics and anticonvulsants. Trends in Pharmacological Science. 8, 57-65.
LaRoche SM & Helmers SL. 2004. The new antiepileptic drugs. Journal of the American Medical Association. 291, 605-614.
Sunday, December 9, 2007
Seizure First Aid
Don't We Already Know What To Do?
There is probably very little point in even writing this- cause we all know that when you witness a seizure, you try and open the person's mouth so that they don't swallow their tongue. Then you call them an ambulance. Right?
WRONG!
If you were reading the above paragraph to yourself thinking "yup, yup, right, exactly!" ... then please read below in great detail. Then re-read it.
Witnessing a Seizure.
Witnessing a seizure for the first time is difficult. It is important to know that the person having a generalized seizure is not in pain and is not conscious. Many people feel scared when they witness a seizure. This is OK. Take a deep breath and know that you can be a significant help to the person having the seizure by following a few simple steps.
What To Do.
- Stay calm.
- Ensure your own safety. If you can't safely approach the individual, then simply stand back.
- If possible, make sure the individual having the seizure is not in harm's way (eg, street, subway, etc.).
- Place something soft under their head so they don’t hit it.
- Pay attention to the length of the seizure (only call an ambulance if the seizure lasts more than 5 minutes).
- Maintain a free space around the individual, don’t allow crowding.
- Once the individual stops moving, try and place them on their side. There is a chance they could vomit. Being on their side ensures their safety from choking.
- The individual may be disoriented after a seizure so be careful not to frighten them. They could react violently if you try to grab them (imagine what you'd do if you woke up disoriented to a stranger grabbing you).
- Try and stay (or find someone to stay) with the individual until they recover fully (5 to 20 minutes). Sadly, there have been reports of people being robbed during a seizure. Even if you can't do any of the above, try to stick around and watch over the person. When they regain consciousness, gently let them know that they have had a seizure and that everything is OK.
What To Avoid Doing.
- Do not try and open the individual’s mouth or place anything in their mouth. Their jaw is locked shut during a tonic-clonic seizure and trying to open their mouth could damage their jaw. There is no risk of them swallowing their tongue.
- Do not try and pin the individual down.
- Do not call an ambulance/911 unless the seizure lasts longer than 5 minutes. Although scary, a seizure is not a medical emergency. The individual who had the seizure is the one who ends up having to pay for the ambulance ride.
There is probably very little point in even writing this- cause we all know that when you witness a seizure, you try and open the person's mouth so that they don't swallow their tongue. Then you call them an ambulance. Right?
WRONG!
If you were reading the above paragraph to yourself thinking "yup, yup, right, exactly!" ... then please read below in great detail. Then re-read it.
Witnessing a Seizure.
Witnessing a seizure for the first time is difficult. It is important to know that the person having a generalized seizure is not in pain and is not conscious. Many people feel scared when they witness a seizure. This is OK. Take a deep breath and know that you can be a significant help to the person having the seizure by following a few simple steps.
What To Do.
- Stay calm.
- Ensure your own safety. If you can't safely approach the individual, then simply stand back.
- If possible, make sure the individual having the seizure is not in harm's way (eg, street, subway, etc.).
- Place something soft under their head so they don’t hit it.
- Pay attention to the length of the seizure (only call an ambulance if the seizure lasts more than 5 minutes).
- Maintain a free space around the individual, don’t allow crowding.
- Once the individual stops moving, try and place them on their side. There is a chance they could vomit. Being on their side ensures their safety from choking.
- The individual may be disoriented after a seizure so be careful not to frighten them. They could react violently if you try to grab them (imagine what you'd do if you woke up disoriented to a stranger grabbing you).
- Try and stay (or find someone to stay) with the individual until they recover fully (5 to 20 minutes). Sadly, there have been reports of people being robbed during a seizure. Even if you can't do any of the above, try to stick around and watch over the person. When they regain consciousness, gently let them know that they have had a seizure and that everything is OK.
What To Avoid Doing.
- Do not try and open the individual’s mouth or place anything in their mouth. Their jaw is locked shut during a tonic-clonic seizure and trying to open their mouth could damage their jaw. There is no risk of them swallowing their tongue.
- Do not try and pin the individual down.
- Do not call an ambulance/911 unless the seizure lasts longer than 5 minutes. Although scary, a seizure is not a medical emergency. The individual who had the seizure is the one who ends up having to pay for the ambulance ride.
What is Epilepsy? What is a Seizure?
Some simplified terms.
Neuron: Also called brain cells. These are the basic building blocks of our brain. They signal (both chemically and electrically) to one another, resulting in our behaviors.
Behavior: What we do.
What is epilepsy?
Epilepsy is a disorder characterized by a wide spectrum of seizures. I will describe the seizure types later, but they range from very brief staring spells to the much stereotyped jerking and flexing of the arms and legs. A diagnosis of epilepsy is made after more than one unprovoked seizure. About 1% of the population has epilepsy.
What is a seizure?
The definition of "seizure" is not completely agreed upon. What we do know is that a seizure consists of a change in brain activity that results in a disruption of our normal behavior. If you give any more detail than that, then people start to argue. Generally speaking, however, people agree that a seizure has elements of "synchrony" and "hyper-excitation".
Normally, brain activity is "chaotic". When you hook someone up to an electroencephalogram (EEG, a machine that measures brain waves) you see very random looking, unpredictable activity (does anyone else find it ironic that chaotic activity is required to generate "normal" behavior**). Synchrony occurs when groups of neurons (called "networks") begin to fire together. "Why" and "how" our neurons become synchronous is not known. It is one of the many mysteries of a very complex system that is being studied by epilepsy researchers.
Seizures are also said to involve hyper-excitation. Brain activity consists of excitatory and inhibitory signals. The analogy often used is that of a car. A car has both an accelerator (excitatory) and brakes (inhibitory). For normal driving, a combination of accelerating and braking is necessary. During a seizure, however, this balance is lost and the brain becomes hyper-excitable. This is where the analogy falls apart because someone having a seizure isn't the same as someone driving off the road and crashing. Rather, they show the behavior of whatever brain region is over-excitable. If the seizure is in a motor area of the brain, then they have a seizure involving motor actions- such as arm and leg movements. If the seizure is in the visual area of the brain, then they may see flashing lights or odd visual patterns.
Types of Seizures.
Seizures types are divided into one of two categories: "generalized seizures" or "partial seizures". A generalized seizure is thought to involve all brain regions at once. One example of a generalized seizure is a "tonic-clonic" seizure (formerly called grand mal seizures). Tonic-clonic seizures are what many people imagine when they hear the word "epilepsy". They involve falling to the ground and shaking of the arms and legs. This movement is the result of the contraction and relaxation of several muscle groups. I know I said that seizures occur in the brain, but these brain cells activate nerve cells in our spinal cord that cause our muscles to contract or relax. Another type of generalized seizure is an absence seizure (formerly called petit mal seizures). Absence seizures involve staring spells, and sometimes rapid blinking of the eyes. Children with absence seizures are often accused of being inattentive or day-dreamers before they are diagnosed with this type of seizure. People are unconscious during all generalized seizures.
A partial seizure, on the other hand, is confined to a specific brain region and is often described as being "focal". An example of a partial seizure is a "simple partial" seizure. Individuals are conscious during simple partial seizures. They may sense flashing lights, feelings of anxiety, hear strange noises or smell a bad smell - depending on the area of the brain involved in the seizure. A partial seizure, however, may spread to other regions of the brain and become generalized. An example of this type of seizure is a "complex partial" seizure. If the simple partial seizure causes a sensation before the seizure generalizes, that individual is said to have an "aura". Auras can be helpful in alerting the individual that they are about to have a generalized seizure. During a complex partial seizure the individual is said to be in an altered state of consciousness. They may appear conscious and responsive, but they will have no recollection of seizure or the events that occurred during the seizure. There are several reports of people doing elaborate activities during a complex partial seizure. One of my favorite stories is of a woman who, during a complex partial seizure, prepared place-settings with her china and cutlery -- on the kitchen floor.
What Causes a Seizure?
Seizures are classified either as "cryptogenic" or "symptomatic". About 60-70% of seizures are cryptogenic- meaning they have no apparent cause. In reality, this means that we don't have the imaging technology to see where the problem is yet. Some of the cryptogenic seizures are genetic, meaning a genetic abnormality changes the way the brain works, making it more susceptible to seizures. This would not show up on an imaging test - and we need to develop better functional tests to screen for these seizure types.
About 30-40% of seizures are symptomatic. This means they have a known underlying problem (eg, brain injury, tumor, known chemical imbalance, etc.). These problems are thought to lower the "seizure threshold" in the brain. The seizure threshold can be defined as the minimal stimulus required to elicit a seizure. Don’t think of "stimulus" in the sense of an electrical shock. Rather, think of it in the sense of whether a cup of coffee, a stressful drive, or poor night's sleep will cause you to have a seizure. People with epilepsy are thought to have a chronically low seizure threshold. This is to say, there is something about the wiring or chemical milieu of their brains that predisposes them to seizure activity.
OK, that's a head-full for now. More to come ...
Kirk.
**I say "normal" behavior because my wise Mother always reminds me that "normal" is just a cycle on your washing machine.
Reference:
Much of the above information was distilled from Dr.W.M.Burnham's excellent article entitled "Epilepsy" from the Encyclopedia of Cognitive Science. (2006) John Wiley & Sons, Ltd.
Why Start a Blog on Epilepsy?
Welcome to the "Epilepsy in a Nutshell" blog!
Why start a blog on Epilepsy? The answer is fairly simple. We are entering a new age in health care where patients (and family/friends of patients) want to empower themselves with information. The flow of knowledge from clinical and basic science realms- especially as it pertains to epilepsy- is not readily accessible. Therefore, the purpose of this blog is to distill and relay important information to those of you living with epilepsy.
The title "Epilepsy in a Nutshell" harkens back to my grade 9 science class where my teacher used to tell us "it's all up there in a nutshell grade 9". This was his way of empowering us to use our brains and sort through the problems. The title isn't meant to suggest that epilepsy is a simple subject. On the contrary- there is nothing more challenging than trying to understand how the brain works, or why it isn't working the way we want it to. As you probably already know, there are no easy answers in this field. Fundamental questions like "what is a seizure", "who gets epilepsy" and "what is the best treatment for my seizures" are still being debated. Regardless, I will address all of these questions here and together we can try and make sense of it all.
I will make a few blog posts today, just to populate the blog. My goal is to make one or two posts each week. Inevitably, I will post information on "what is epilepsy", etc. But, there are many sites out there already dealing with that (see links). My vision for this site is to address issues facing those living with epilepsy.
Well, I hope you find the information posted here useful. Please feel free to comment below or email me if you want me to review a specific topic. I will do my best to cover many of the relevant topics facing those living with epilepsy. To keep things exciting, I will also call on colleagues and mentors from time-to-time to post the "latest and greatest" in their subfield of epilepsy research.
So here we go ...
Why start a blog on Epilepsy? The answer is fairly simple. We are entering a new age in health care where patients (and family/friends of patients) want to empower themselves with information. The flow of knowledge from clinical and basic science realms- especially as it pertains to epilepsy- is not readily accessible. Therefore, the purpose of this blog is to distill and relay important information to those of you living with epilepsy.
The title "Epilepsy in a Nutshell" harkens back to my grade 9 science class where my teacher used to tell us "it's all up there in a nutshell grade 9". This was his way of empowering us to use our brains and sort through the problems. The title isn't meant to suggest that epilepsy is a simple subject. On the contrary- there is nothing more challenging than trying to understand how the brain works, or why it isn't working the way we want it to. As you probably already know, there are no easy answers in this field. Fundamental questions like "what is a seizure", "who gets epilepsy" and "what is the best treatment for my seizures" are still being debated. Regardless, I will address all of these questions here and together we can try and make sense of it all.
I will make a few blog posts today, just to populate the blog. My goal is to make one or two posts each week. Inevitably, I will post information on "what is epilepsy", etc. But, there are many sites out there already dealing with that (see links). My vision for this site is to address issues facing those living with epilepsy.
Well, I hope you find the information posted here useful. Please feel free to comment below or email me if you want me to review a specific topic. I will do my best to cover many of the relevant topics facing those living with epilepsy. To keep things exciting, I will also call on colleagues and mentors from time-to-time to post the "latest and greatest" in their subfield of epilepsy research.
So here we go ...
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