It would be so nice if neurological tests gave clear answers. Either you have seizures, or you don’t; either you have Lennox-Gastaut syndrome, or you don’t. As neurologists, however, we often face diagnostic uncertainty. Sometimes a diagnosis depends on the interpretation of results. Sometimes the diagnosis depends on how the symptoms progress with time.
Here is a case that illustrates my own struggles with diagnostic uncertainty. Years ago, a 2-year-old girl came to our emergency room with her first seizure.
Questions I ask
When I talk to families about a seizure, I want to know:
What was the first sign something was wrong? This can help classify the type of seizure.
What did the person’s eyes, arms and legs do during the seizure? This can also help classify the type of seizure.
How long did it last? Most seizures last between 1-3 minutes, but this can feel like a very long time.
What happened after the seizure stopped? Usually people will report post-ictal symptoms, like sleepiness and confusion.
In this case, my patient was playing on the floor with her toys and suddenly fell over. Parents reported she was unresponsive, staring, and limp for about two minutes. Her lips and fingers turned slightly blue. She then returned to consciousness but was confused.
By the time she arrived in the emergency room she responded like any other healthy, alert two-year-old.
Medical history and testing
This patient had no recent history of head trauma, no fever or other signs of infection, and no ingestions of medications around the home (a frequent cause of sudden change in a two-year-old). This is a fairly typical story, and could have been a single event with no need for extensive workup or medication.
But this patient had another seizure in the emergency room, followed by several more over the next week. She was admitted to the hospital for treatment and workup.
Her first electroencephalogram was normal, which made her seizures more likely to be focal – arising from one area of the brain. Her brain MRI was also normal, which was reassuring. Bloodwork looking for a possible metabolic disorder was normal. Genetic testing (an epilepsy gene panel) did not reveal a cause for seizures.
The first medication we tried helped initially, but seizures returned. We switched her to oxcarbazepine, a medication that can work very well for focal seizures. With this medication, she started having seizures involving a sudden fall from standing or sitting – atonic seizures.
This was our first clue that something very different was going on. Another EEG showed us slow, 2 Hz, spike-wave formations—plus tonic seizures, atonic seizures, and myoclonic seizures.
Diagnosis and outcomes
I talked with my patient’s family about the diagnosis of Lennox-Gastaut syndrome. She had atonic seizures, myoclonic seizures, and tonic seizures, and probable atypical absence seizures, as well as slow spike-and-wave on her EEG. These findings fit with the first two criteria for Lennox-Gastaut syndrome – although she did not have generalized paroxysmal fast activity captures, or atypical absence seizures. She didn’t have the third part of the LGS triad: an increase in intellectual impairment, psychomotor slowing, or developmental abnormalities.
This was hard to talk about. Their little girl – smart, affectionate, verbal, curious – might have cognitive changes with time. I didn’t know if we could do anything to prevent it.
Over the next months, we tried other medications, and finally found one that worked without side effects. Months passed, and family reported no seizures.
After two years of seizure freedom, we discussed risks and benefits, and opted to wean off the medication. She remains free of seizures, and now is doing well in school, with no neurological concerns.Related: Supporting caregivers of young patients with LGS
Reflections and takeaways
Did my patient truly have Lennox-Gastaut syndrome and grow out of it? With multiple medication-resistant seizure types and specific abnormalities on EEG, she met two of three criteria—and the third criterion, mild to severe decrease in intelligence, can be difficult to assess in a small child. Now that she’s older and doing well off all medications, I do question whether that was truly the “correct” diagnosis—and I am very happy to be wrong.
Takeaways to note:
The diagnostic criteria for Lennox-Gastaut syndrome includes 1) multiple seizure types, including tonic, atypical absence, and atonic, and sometimes myoclonic or generalized tonic-clonic; 2) EEG findings including slow (<2 Hz) spike-and-wave and generalized paroxysmal fast activity; and 3) mild to severe intellectual impairment or psychomotor regression.
Most of our tests in neurology, including EEG or MRI, have inter-reader variability—meaning that physicians may debate complicated findings on the same test, without a clear right answer.
Because the diagnosis of Lennox-Gastaut syndrome involves tests like EEG; because other seizure disorders can have multiple seizure types; and because the syndrome can evolve over time, it can be challenging to state with absolute certainty that this is the diagnosis.
Like my patient, up to 1 in 4 children diagnosed with LGS have no identified cause. It can be incredibly frustrating for both families and physicians when we can’t identify the cause of seizures. Some causes of LGS include congenital structural abnormalities of the brain, like polymicrogyria, schizencephaly, or tuberous sclerosis; injury to the brain from head trauma or perinatal hypoxic ischemia; or genetic variations (which may not show up on a genetic panel).