When do we say seizures are refractory to medicines?

                                 When do we say seizures are refractory to medicines?

                                                        Nitin.K.Sethi, MD

Assistant Professor of Neurology

New York-Presbyterian Hospital

Weill Cornell Medical Center

New York, NY 10065

 

Yesterday I saw a patient with medically refractory epilepsy in my office. As I took pains to explain to the family about refractory seizures, I realised that understanding the same can be difficult for a lay person. So in this post I shall talk about refractory seizures.

So what do I mean if I say a patient has medically refractory epilepsy or medically refractory seizure disorder? In simple words all I am saying is that the patient has a seizure disorder which has not shown an adequate response to anti-seizure medicines.

In most patients with epilepsy/ seizure disorder, adequate seizure control can be obtained by just one seizure medicine. By adequate control I mean no more seizures. No more seizures, the side-effects of the anti-seizure medication used are tolerable (if none that is the best): the patient is happy and I am happy. While good control of seizures can be obtained in the majority of patients, there are a few in whom the seizures are harder to control. You use one seizure medicine but the seizures still persist, you stop the first and use a second-still seizures, you try a third-same story. You start using 2 or more drugs together (at the same time) to try control the seizures. This is referred to as polytherapy or polypharmacy.  You can imagine what happens next. The patient is on 3 and at times more drugs, more side-effects, more drug-drug interaction and at times still poor seizure control. The patient feels miserable and I am not happy too. Such a patient has medically intractable epilepsy, seizures are refractory to medications.

So what can be done for a patient who has medically refractory epilepsy? Can we offer them something to control their seizures. I am happy to say yes. Patients with medically refractory epilepsy should be ideally seen in specialized epilepsy centers (comprehensive epilepsy centers).  These centers offer expertise: patients can be enrolled in trials of experimental drugs, other options like neurostimulation (vagus nerve stimulator) and finally epilepsy surgery can be explored (see my post on epilepsy surgery at http://braindiseases.info) .

Seizures due to hypoglycemia (low blood sugar)

Seizures in the setting of hypoglycemia are well described. The brain needs sugar to function and when the blood sugar falls “too low”, one of the things that can happen is that the patient may have a seizure (this is usually a generalized convulsion-a tonic-clonic or Grand Mal seizure). There is no one level of blood sugar below which one has a seizure (rather the level varies from person to person). Let me explain that with an example. Lets assume you are a diabetic and you take your insulin shot but for once forget to take a meal (maybe you are a hard working executive on the run). You have a convulsion while at work and are taken to the nearest ER. There your blood sugar at the time of presentation is recorded to be 60 mg/dl. There might be another similar patient whose blood sugar falls to 52mg/dl yet he does not have a convulsion. So there is no set limit below which the brain shall have a seizure but speaking in broader terms usually the brain does not tolerate blood sugar below 60mg/dl and below 40 mg/dl most patients shall be symptomatic (either have a convulsion or be confused and obtunded. The term used for this constellation of neurological signs and symptoms as a result of hypoglycemia is NEUROHYPOGLYCEMIA).

The good news though is that seizures due to hypoglycemia are readily treatable. In the ER we load the patient with glucose (usually this is given via an intravenous drip as the patient is obtunded and confused and cannot accept anything from the mouth). The blood sugar quickly rises and the seizures stop. Patients who suffer from hypoglycemic seizures do not need to be on an anti-epileptic drug. These patients do not have epilepsy. If their blood sugar does not fall down again, they will not have another seizure.

Rather a meticulous search should be conducted to find out the cause of hypoglycemia:

-is the patient a diabetic who took too much insulin by mistake?

 -did he miss his meal but took his insulin?

-is there any other cause of hypoglycemia such an insulin secreting tumor?

-is the patient septic?

Hypoglycemic seizures are most commonly seen in diabetics. This emphasizes the importance of good glycemic control in this vulnerable population.

Nitin Sethi, MD

Complex partial seizures/ temporal lobe epilepsy

One of the most common type of seizures seen in the adult population is what are called complex partial seizures. As the name suggests these are partial seizures  meaning that only a part of the brain has the seizure (remember in generalized seizures the whole brain has the seizure and hence the patient clinically has a convulsion, read my posts on epilepsy and seizures at http://braindiseases.info). Complex partial seizures differ from simple partial seizures. While in simple partial seizures there is no disturbance in the patient’s level of consciousness (the patient is awake and alert), in complex partial seizures there is an impairment in the level of consciousness. The patient may have his or her eyes open but usually is unable to respond or communicate. He may or may not comprehend if you try to speak to him during a seizure episode.

As many of the complex partial seizures arise from the temporal lobes in the brain, epilepsy of this kind is also referred to as temporal lobe epilepsy (TLE). That said and done complex partial seizures may also arise from the frontal lobes. Seizures arising from the frontal lobes can present with bizzare clinical manifestations, patient may become hyperactive during the seizure and have strange bicycling like movements of the legs. Complex partial seizures are at times associated with an aura. A simple way to define aura is what happens usually before the seizure. Prior to the onset of a seizure, the patient may experience gustatory or olfactory auras (smell of burning rubber, metallic taste in the mouth are the different classical auras mentioned in the textbooks of neurology). Other patients may mention they “feel wierd” or “dizzy”. Others mention a rising sensation in the stomach.

During the seizure apart from impairment in the level of consciousness, patients frequently exhibit what we refer to as automatisms. These are semi-purposeful movements. Examples include lip-smacking, chewing movements, tongue protusion, picking at the clothes (semi-purposeful movements of the hands). These patients may or may not have a “convulsion”. If the seizure spreads and becomes generalized then they go into a convulsion (such seizures are referred to as partial with secondary generalization).

If an adult presents with a new onset complex partial seizure, neuroimaging is warranted. This is because a new onset complex partial seizure raises the suspicion for an underlying structural lesion in the brain such as a cyst or a tumor (though I want to emphasize here that the most common cause of new onset seizures in the elderly is vascular, meaning a previous stroke).

Work-up for TLE includes an EEG, if needed a long term EEG recording (we call this a video-EEG study), imaging studies like CT scan (though the study of choice is what is called a MRI scan of the brain done under the epilepsy protocol). Thin slices are taken to look at the temporal lobes and hippocampus to make sure there is no structural lesion there nor is there any evidence for mesial temporal sclerosis (MTS).

There are many effective drugs for complex partial seizures/TLE. The most commonly used are carbamazepine (Tegretol) and oxcarbazepine (trileptal). If the seizures are refractory to medications, these patients can be worked up for epilepsy surgery (see my post on epilepsy surgery at http://braindiseases.info).

Nitin Sethi, MD

Seizures associated with alcohol intake

In this post I thought I shall discuss the effects of alcohol on the brain especially with respect to seizures. Many people drink socially , a drink or two after work is not only relaxing but also enjoyable. But who is an alcoholic or rather when does one have a drinking problem? We doctors use the CAGE criteria as a rather simple questionaire to determine if someone has a drinking problem.

“CAGE” where each letter has a question attached to it and the person has to answer yes or no. Let me elaborate a little.

C–stands for “cutting down”–have you ever felt the need to cut down on your drinking?

A–stands for “anger”—have you ever felt angry if someone has questioned your drinking habit?

G–stands for “guilt”—have you ever felt guilty about your drinking?

E– stands for “eyeopener”–have you ever taken a drink first thing in the morning?

If the person answers yes to these questions, he or she may have a drinking problem. What though is the effect of heavy alcohol drinking on the brain? Does it actually kill brain cells (neurons)? Does it lead to dementia? Can too many drinks cause a seizure?

Alcohol contrary to popular beliefs is a CNS depressant and not a stimulant. Alcohol is rather rapidly absorbed through the lining of the stomach and enters the blood stream from where it is carried to the brain. In the brain, it acts on the neurons and initially causes a loss of inhibition. You loosen up, your speech flows more smoothly and soon you become the life of the party. Well as you continue to drink, alcohol then starts depressing the central nervous system (CNS) . People usually fall asleep soon after consuming alcohol.

But let us get back to how chronic alcohol intake affects the CNS especially with respect to seizures.

I shall discuss this one by one.

Alcohol induced seizures

 

 Heavy alcohol consumption can induce seizures. Alcohol induced seizures are of different types. One is what is commonly referred to as “rum fits”. Let me explain with an example. You are out with your friends celebrating a promotion. Your drink for the night is beer. Your normal “limit” is say 4 beers. But hey you are celebrating and so you end up binging. Before you know it you are on your 10th beer of the night. Right as you are having your 11th beer, your eyes roll up and you have a big generalized tonic-clonic convulsion (see my posts on epilepsy on my website http://braindiseases.info) . This kind of seizure which occurs at the height of binging is what has been referred to as a “rum” fit. I guess it was first described with respect to rum. Any of us can have a rum fit if we drink too much alcohol. You do not need to be an epileptic to have a rum fit, though I feel these kinds of seizures associated with alcohol binging are more common in patients who have an underlying seizure tendency. Thus if you are an epileptic you are more likely to have a rum fit if you overindulge in alcohol as regards to someone who does not have a seizure tendency. Hence I always advise my seizure patients to drink alcohol in moderation. You can drink and by all means enjoy your occasional drink but do not overindulge in this pleasure. Know when to say no and walk out of the bar.

Another type of seizure associated with alcohol is what is called “Alcohol Withdrawal Seizure”. Here the seizure occurs in a different scenario. Usually the person is one who is a chronic alcohol drinker, one who is dependent on alcohol and feels uneasy and restless if he does not drink everyday. Let us now assume he suddenly stops drinking for whatever reason. Maybe he runs out of money and cannot buy alcohol. Usually 24 to 48 hours after his last drink, this patient may have a generalized tonic clonic convulsion. As this seizure occurs in the setting of a withdrawal from alcohol, it is called alcohol withdrawal seizure. It is important that heavy and chronic alcohol drinkers keep this is mind and do not suddenly stop drinking. If a person does decide to quit alcohol he should do it under medical supervision.

Now for the third setting in which seizures might occur with alcohol. Again we have a person who is an alcoholic (heavy and chronic alcohol user). Again for some reason he suddenly stops drinking. Uusally after 72 hours, he starts becoming delirious (confused), he has autonomic dysfunction and is tachycardic, sweating profusely, his blood pressure is up. Such a patient is said to be in what we refer to as “delirium tremens” (DT) . Patient who are in DT may have a flurry of seizures one after the other. DT is a life threatening condition and a patient may die if not treated in time. Usually patients are admitted to the intensive care unit of the hospital. We hydrate them aggressively, we give them medications to calm them down. Lorazepam (Ativan) or other benzodiazepines like chordiazepoxide (Librium) are given to prevent seizures and treat acute alcohol withdrawal.

Patients who have had a rum fit, an alcohol withdrawal seizure or even DT do not warrant long term treatment with an antiepileptic drug. These patients do not have epilepsy. If they abstain from drinking in the future it is more than likely that they may never have a seizure again in their lifetime. However there are a few patients whom we feel have a high risk for seizure recurrence, in such patients we may prescribe antiepileptic drug therapy for some time (the duration of the therapy varies depending upon the history, examination findings and the results of investigations like EEG and CT scan or MRI brain)

I have tried to give an overview of the kinds of seizures associated with alcohol intake. Like I stated earlier one need not be an epileptic to have seizures associated with alcohol intake. I try to explain this to my patients as follows. The brain has a threshold for the amount of alcohol it can tolerate. This threshold varies from person to person. If you drink above that threshold, the brain does not like it and one way it reacts is by having a seizure. This “threshold” is lower in patients who have an underlying seizure tendency. In these epileptic patients, a small amount of alcohol may induce a seizure. Also if you mix your drinks or combine alcohol consumption with other recreational drugs like cocaine you are creating the ideal grounds to have a seizure. Certain medicines like antibiotics also lower your seizure threshold and hence should not be used along with alcohol.

Patients with epilepsy should discuss about alcohol consumption with their doctors because at times we doctors do not initiate this discussion of our own. If you have seizures my advise to you would be to drink in moderation and not exceed your limits.

Nitin Sethi, MD

Erectile dysfunction-some neurological causes

I thought I would discuss some neurological causes of erectile dysfunction and decreased libido. There are many neurological diseases which are associated with erectile dysfunction and may also result in decreased libido. One of the most common is diabetic autonomic neuropathy. Diabetic patients especially those who have autonomic neuropathy (dysautonomia) frequently have erectile dyfunction. Supprisingly many do not volunteer this information, unless their doctor asks about it. They may complain of other symptoms of neuropathy like pain and numbess in their hands and feet but may not volunteer the history that they are having erectile dysfunction. Many patients do not realize that their erectile problems are a part and parcel of their uncontrolled diabetes.

Erectile problems and decrease libido is also frequently seen in patients who have multiple sclerosis. Fortunately this aspect of MS is now been given increasing recognition by doctors and a discussion is initiated with the patient at some stage of their treatment. Women with MS may have complaints of decreased vaginal lubrication, loss of vaginal muscle tone and diminished clitoral engorgement.
All this can lead to a decrease or loss of sex drive. Decreased or unpleasant genital sensations may lead to a diminished capacity for orgasm. Men with MS experience  erectile dysfunction and a decrease in or loss of ejaculatory force or frequency.

Erectile dysfunction and sexual difficulties are also a part and parcel of certain neurodegenerative conditions like multi system atrophy especially a syndrome called Shy Drager Syndrome in which autonomic failure is prominent. Parkinsons disease and patients with degenerative dementias may also have some of these problems. In these patients the cause is usually multifactorial.

Patients with epilepsy also frequently have sexual dysfunction. Again the causes are multifactorial but one important reversible cause is drug side-effects. Some anti-epileptic drugs and antidepressants frequently cause sexual dysfunction as a side-effect.

The good news is that sexual dysfunction is now more readily recognized as a part and parcel of certain neurological disorders. Neurologists are nowdays more adept in asking patients about it. It is important that patients volunteer information if they are experiencing sexual dysfunction as many of the causes are treatable. Drugs with sexual dysfunction as a side-effect can be stopped and replaced with other drugs. Also some of the symptoms can be ameriolated by using medications like sildenafil (Viagra).

Personal Regards,

Nitin Sethi, MD

Mind-body interventions: applications in neurology

A comprehensive review  on mind-body interventions and its application in various neurological disorders was recently published in Neurology. The authors Wahbeh, Elas and Oken searched Medline and PsychoInfo databases to identify clinical trials, reviews and published evidence on mind-body therapies and neurological diseases.

Meditation, relaxation, breathing exercises, yoga, tai-chi, qigong, hypnosis and biofeedback are some of the mind-body interventions that have been used in various neurological conditions like general pain, back and neck pain, carpel tunnel syndrome, headaches (migraine and tension), fibromyalgia, multiple sclerosis, epilepsy, neuromuscular diseases, stroke, falls with aging, Parkinson disease, stroke and attention deficit hyperactivity disorder (ADHD).

The authors do a good job in shifting through all the data to try to identify the effectiveness of mind-body interventions. As they point out in their discussion , many patients as many as 62% use complementary and alternative medicine therapies (CAM). Some with and many without the knowledge of their physicians. One of the reason why CAM therapies are popular is that they are relatively easy to implement, cheap (though many patients have to pay out of their pocket. Some insurance companies shall reimburse if you have a letter from your doctor) and more importantly as the authors point out it makes the patients feel empowered. They feel that they are in control of some of the decision making in their disease process and treatment. Moreover it gives a sense of general well being.

The authors righly point out that is difficult to scientifically judge whether these interventions are all effective. The reason for this is that many of the studies included small number of subjects and some of them did not have a control group. Moreover it is hard to blind these studies so as to avoid a placebo effect. Like suppose I want to study whether acupuncture is effective for lower back pain. One group I give acupuncture. Ideally I should have a control, a group which receives sham acupuncture so as to null the placebo effect. Now this is difficult to implement.

Th authors in their review conclude that there are several neurological conditions where the evidence in favor of mind-body therapies is quite strong such as migraine headaches. In other conditions the evidence is limited due to small clincial trials and inadequate control group.

It is reasonable to conclude that CAM therapies like yoga, tai-chi and qigong improve balance in the elderly and decrease the incidence of falls. Moreover they give a sense of well being and happiness. Meditation exercises whether it is mindfulness meditation, transcendental meditation or concentration meditation with the repetition of a word like Om or a mantra

“Hare Krishna Hare Krishna

Krishna Krishna Hare Hare 

Hare Rama Hare Rama

Rama Rama Hare Hare”

all help in relaxation and reducing stress. This may decrease blood pressure and reduce the incidence of strokes and heart attacks. Brain changes have been observes during meditation in EEG and imaging studies and there is evidence that these exercises have wide spread effects on the endocrine and immune systems as well neurotransmitters. Hatha yoga may help in improving mobility and balance and thus decreasing fall risk. As the authors point out righly Bikram yoga  which is carried out in very hot temperatures is likely not good for patients with MS, as it may worsen their weakness. This is called Uhthoff phenomena.

There is also some evidence to suggest benefits of these interventions in patients who have chronic lower back and neck pain, those with fibromyalgia, osteoarthritis as well as carpel tunnel syndrome (some studies suggest benefit while others do not).

My advise to patients who want to try out CAM therapies for various neurological conditions is to take their doctors into confidence. It is likely that some of these therapies when used along with allopathic medicines shall give added benefits and likely make you feel better. Like with any other therapy one must find a knowledgeable practitioner who knows what he or she is doing.

Then one can truly reap the benefits of these ancient therapies.

Personal Regards,

Nitin Sethi, MD

Driving with epilepsy: when to start?

One of the big ways in which epilepsy and seizures negatively affect quality of life is by the restrictions they impose on driving. So should patients with epilepsy be allowed to drive and if so when? Is it safe from them to drive?

All these are genuine questions for which patients frequently seek answers. Well lets tackle them one by one. Normally if you have a new onset seizure (your first seizure ever) and present to the hospital, your doctor shall ask you not to drive at least till the seizure work up is complete. The seizure workup shall determine what is the cause of your seizure, do you need to be on a seizure medication, if yes for how long and what are the chances that you are going to have another seizure.

If the cause of seizure is found to be reversible, lets say for example you are diabetic and have a seizure when your blood sugar suddenly fell down as you took your insulin shot but missed a meal. Now this is a reversible cause of seizure and the patient does not have epilepsy. If his blood sugar does not fall down again, he may never have a second seizure. In this case the answer is simple and yes the patient can drive.

Lets take another example, a patient has poorly controlled epilepsy and is brought to the hospital after a seizure at work. In this case, the doctor shall rightly advise the patient not to drive. A patient like this is liable to have another seizure and may injure himself or hurt others if he is behind the wheel.

But this does not mean, that a patient with epilepsy can never drive. If your seizures have been well controlled on medication for a period of 2 years, you may discuss driving again with your doctor. Drving laws with respect to epilepsy vary from state to state in USA. In the state of New York, as a physician I am not mandated by law to report my patient with epilepsy to the DMV. It is left to the patient’s own good judgement that he or she shall surrender their driving license and not drive. In the state of New Jersy though, physicians are mandated by law to report seizure patients to the DMV.

You should be aware of the laws in your state and should discuss the same with your doctor. Most of the bylaws can be found on the DMV website and are listed for each state.

I hope you found this information useful. Its wednesday night and the clock strikes 10pm. I think my bed is calling. Have a good night everyone.

Personal Regards,

Nitin Sethi, MD