It Walks Like a Duck and Talks Like a Duck…. But It’s a Lizard

DiagnosisPNES

30 Jul

Name & title: Jim Siegler, Assistant Professor of Neurology, MD

Cool fact: Jim is the Founder of BrainWaves: an academic audio podcast whose mission is to educate medical providers through clinical cases and topical reviews in neurology and medicine.

Epilepsy seems like a pretty straightforward diagnosis to make. If you have seizures, basically you have epilepsy, right?

Wrong.

It turns out, there are very specific criteria that have been provided by internationally recognized and peer-reviewed collaborations¹. According to the International League Against Epilepsy² (ILAE), the world’s foremost authority on the matter, a patient is diagnosed with epilepsy if they meet any of the following 3 criteria:

Two unprovoked seizures >24 hours apart
One unprovoked seizure and a high probability (60% chance) of a second unprovoked seizure in the next 10 years
An epilepsy syndrome

The reason for such stringent criteria is based on a simple concept. Is the juice worth the squeeze? Let’s think about it. The reason doctors make a diagnosis of epilepsy is to justify to themselves (and to the patients) whether it is the right move to treat a patient who has experienced a seizure. The fact of the matter is, as many as 1 in 10 people worldwide will experience a seizure in their lifetime, but only 3% will have recurrent seizures. ³

Therefore, having a single seizure doesn’t necessarily justify treatment to prevent future seizures⁴. All elements of the patient’s history, physical exam, brain imaging, and electroencephalography⁵ (EEG) should be taken into careful consideration before an epilepsy diagnosis is made and the patient is started a medication.

You probably knew all this.

What you might not have known is all that shakes is not seizure. There is an enormous range of what seizures can look like, which I briefly reviewed on my blog for neurology education⁶, so it makes sense that a lot of patients, bystanders, and even physicians have trouble deciphering what is a seizure and what is not. For example, a lot of funny baby movements and “staring spells” are simply normal behaviours. And for adults, a lot of jerking movements can be normal when they faint. These are not seizures, but the only way to definitively tell is by testing the patient using EEG.

But if you don’t have an EEG, you’re not entirely out of luck. There are some features of the abnormal behaviours that neurologists recognize more commonly as seizures, and some features that we recognize more commonly as non-epileptic seizures (also known as pseudoseizures, psychogenic non-epileptic seizures, or psychogenic non-epileptic events)⁷. For example, forced eye closure is very rarely seen in epileptic seizures, whereas a forced gaze deviation (meaning eyes forcibly staring to one side) is very commonly seen in epileptic seizures. See the table below for more examples.

What may be confusing is that a patient may look like they are physically having seizures, but the EEG will show both seizure and non-seizure wave forms. This means that some of the abnormal movements or behaviours are actually “electrographic seizures” and some of the behaviours are non-epileptic. It might even surprise you to learn that one-third of patients with epilepsy have non-epileptic events as well as true seizures. And a large number of patients with non-epileptic behaviours may have an underlying diagnosis of epilepsy. The only way to determine if the events are true, electrographic seizures, or if they are non-epileptic, is to perform an EEG at the time of the behaviour.

Now, the EEG is not perfect. It has its own limitations. An EEG can appear normal even during a true seizure. For example, abnormal electrical activity in the brain may take place too deep (and far away) from the superficial recording electrodes. But these are very, very rare. Or the abnormal electrical activity may occur in a very tiny region of the brain that cannot be detected by routine electrode configuration. In fact, an electrographic seizure must involve at least 6 square centimetres of brain tissue in order to be captured by a routine EEG. Anything less than that, and you will probably miss it.

You’re probably asking yourself, what does it matter if the seizures are epileptic or non-epileptic? Well, it matters a lot actually. And some experts have made this abundantly clear in the titles of their manuscripts—such as the paper by Reuber and colleagues called “Failure to recognize psychogenic nonepileptic seizures may cause death⁸.”

Treating PNES⁷ like seizures may lead to innumerable side effects of medications:

Lethargy
Dizziness
Rash, some of which can be fatal
Liver failure
Kidney failure
Medication interactions
Birth defects (in pregnant women)

Treating prolonged “seizures”, when they are non-epileptic, will lead to unnecessary and risky interventions like:

Pharmacologic sedation
Medication-induced paralysis
Mechanical ventilation
ICU hospitalization
Hospital-acquired infection
Deep vein thromboses

Perhaps more importantly, using anti-epileptic drugs to treat non-epileptic events will not help the patient. Sure, there may be some personal satisfaction felt by the patient knowing they are “being treated.” But the underlying cause of the non-epileptic events, whether it is a major stressor in life or difficulty in recovering from a traumatic event, will go unresolved when a patient is started on Lamictal⁹ or Keppra¹⁰. An estimated three quarters of patients with non-epileptic events will have an underlying psychiatric disorder, and depending on the disorder, the patient is more likely to benefit from one form of psychotherapy or another.

But there is hope for these patients. And despite an average delay of 7-10 years for the diagnosis of non-epileptic events, the prognosis is typically quite good. With appropriate neurologic and psychiatric follow-up, behavioural intervention, and management of the underlying cause of PNES, most events will resolve on their own. But this is dependent on the correct diagnosis being made in the first place.