The parents of a toddler noticed that he was having brief muscle twitching – or hypnic jerks – before falling asleep and when waking up.
Several months later, they observe something else: Their son’s speech has plateaued. He’s no longer learning new words. They’re puzzled, but think it might be the result of too much screen time.
The parents take their son to the family doctor and mention both his language delay and the physical twitches. They’re told that the two aren’t related and that hypnic jerks are extremely common and don’t require treatment. There’s no mention of the possibility of paediatric seizures.
Months pass. As they watch their son even more closely, they notice him starting to experience the same muscle twitches throughout the day, unrelated to sleeping and waking. And although their child has a history of normal development, they have a nagging sense that something is terribly wrong … and they’re right.
Over time, the random muscle jerks grow in intensity. They become like electrical jolts, causing his body to suddenly stiffen and then go limp.
The parents return to their family doctor, who refers them to a paediatrician. The paediatrician suspects these episodes might be paediatric seizures and refers him to a paediatric neurologist.
By this time, the boy is also experiencing physical regression along with his cognitive decline. He’s not as steady on his feet as he used to be, and his language development has slowed dramatically.
The tests ordered by the paediatric neurologist indicate the child might have myoclonic-atonic seizures, which cause muscles to jerk and then go limp. Anti-seizure medication is prescribed, but with no effect.
The parents get another opinion, and another. Finally, they meet with Dr. Ebru Arhan, a paediatric neurologist and professor in the department of paediatric neurology at Gazi University in Turkey.
“And I learned that after the seizure started the patient has cognitive regression, like the language plateau,” says Dr. Arhan.
This was Dr. Arhan’s first red flag. Seizures followed by language regression. She had an MRI and EEG taken and got the same results as the previous tests. However, the child’s symptoms had progressed and more information was available that began to point her in the direction of a diagnosis.
Doctors are trained to look at the patient’s history, physical exam, and test results with a critical eye – always reassessing what’s on the DDx, and shuffling the list to put the most likely diagnoses at the top.
And for this young child, their history revealed another clue.
For Healthcare Professionals only.
Dr. Arhan has been compensated by BioMarin for her participation.
Professor Ebru Arhan, MD
Ebru Arhan is associate professor in the Division of Paediatric Neurology, at the Gazi University Faculty of Medicine in Ankara, Turkey. Her international experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests include brain stimulation, traumatic brain injury, and neurological disorders, which are reflected in her wide range of publications in various national and international journals.
DDx SEASON 5, EPISODE 5
Paediatric Seizures and The Race Against Time
RAJ: This season of DDx is sponsored by BioMarin Pharmaceutical Inc.
This podcast is intended for healthcare professionals only.
Some details of this case study have been changed.
RAJ: The parents of a toddler notice that he’s having brief muscle twitching — or hypnic jerks — before falling asleep and when waking up. He’s two-and-a-half years old.
Several months later they observe something else: Their son’s speech has plateaued. He’s no longer learning new words. They’re puzzled, but they think it might be the result of too much screen time.
The parents take their son to their family doctor and mention both his language delay and the physical twitches.
They’re told that the two aren’t related and that hypnic jerks are extremely common and don’t require treatment.
Months pass…. As they watch their son even more closely… they notice that he has started to experience the same muscle twitches throughout the day, unrelated to sleeping and waking.
And although their child has a history of normal development, they have a nagging sense that something is terribly wrong… and they’re right.
Show intro DDx theme music
RAJ: This is DDx, a podcast from Figure 1 about how doctors think.
This season is all about rare paediatric disorders.
I’m Dr. Raj Bhardwaj.
Today’s case comes from Dr. Ebru Arhan, a paediatric neurologist and professor in the Department of Paediatric Neurology at Gazi University in Turkey.
Dr. Arhan has been compensated by BioMarin Pharmaceutical Inc. for her participation in this episode.
Chapter 1: Symptoms
RAJ: Six months after that initial visit to the family doctor, our patient’s random muscle jerks gradually grow in intensity… Now they’re like electrical jolts, causing his body to suddenly stiffen and then go limp.
The parents return to their family doctor, who refers them to a paediatrician.
The paediatrician suspects our patient might have epilepsy and refers him to a paediatric neurologist.
The boy is also experiencing physical regression along with his cognitive decline: he’s not as steady on his feet as he used to be, and his language development has slowed dramatically.
The paediatric neurologist orders an MRI, EEG and other diagnostic tests to try and learn more about the child’s seizures.
The MRI helps to discern if there are any abnormalities or changes in the structure of the brain that could be causing the seizures.
The results are normal.
But the EEG, which monitors the brain’s electrical activity, shows a generalized spike in waves.
This indicates that the child might have myoclonic-atonic seizures, which causes muscles to jerk and then go limp.
Eventually, anti-seizure medication is prescribed.
It has no effect.
The parents want a second opinion.
A second paediatric neurologist re-checks the tests, and adds a second anti-seizure medication… which also has no effect.
Change in tone
The paediatric neurologists heard hoofbeats… and thought “horses” not “zebras”, which is a reasonable conclusion most of the time…
Suddenly, those hoofbeats might not represent what they usually do…
At this point the parents’ anxiety is mounting.
They seek out a third opinion, and our young patient meets Dr. Arhan…
DR. ARHAN: And when the patient came to me, as the third paediatric neurologist, I took the past medical history. And I learned that after the seizure started the patient has cognitive regression, like the language plateau.
RAJ: This was Dr. Arhan’s first red flag. Seizures followed by language regression.
Chapter 2: Diagnosis Tests
RAJ: Dr. Arhan needed to get a closer look at the patient’s brain.
So like the two specialists before her, she ordered an EEG and an MRI.
Once again, the results of the MRI were normal.
But the EEG gave her some valuable information.
DR. ARHAN: We have generalized spike and waves. Also we have a polyspike and waves. Polyspike, means the myoclonic seizure is occurring in the patient. This patient has a myoclonic seizure.
RAJ: The other two specialists also got the same EEG results. But Dr. Arhan had the benefit of time having elapsed. Symptoms were progressing and more information was present to point her in the direction of a diagnosis.
Doctors are trained to look at the patient’s history, physical exam, and test results with a critical eye… always reassessing what’s on the DDx, and shuffling the list to put the most likely diagnoses at the top…
And this young child’s history revealed another clue…
DR. ARHAN: This boy’s regression started after the myoclonic seizures. Our patient was developing normally. He started walking at the age of one year. He started speaking at the age of two, but after the age of two and a half when he first had the myoclonic seizures, his vocabulary was decreasing day by day.
The mother was saying that he was just sometimes looking blank at me. He did not understand what I’m saying. After the severity and the frequency of these myoclonic jerks increased, the parents were anxious.
RAJ: It’s frightening enough to see your child’s development slow and stall… but to watch them lose abilities that they already had is terrifying.
Although metabolic tests also came back normal, there were still more clues for Dr. Arhan to chase down…
DR. ARHAN: He had drug-resistant seizures. This was also a clue for me. If a patient’s seizures are drug resistant then this means it’s not just a simple epilepsy.
RAJ: Dr. Arhan knew she had to act quickly. The patient’s seizures were damaging his brain. Waiting to arrive at a concrete diagnosis before prescribing treatment might do more harm than good.
So she suggested the boy try a high-fat low carbohydrate diet, which can be a remarkably effective tool to manage drug-resistant epilepsy.
DR. ARHAN: I just thought that I have to start a ketogenic diet.
RAJ: Under strict medical supervision, the ketogenic diet forces the body to produce ketones, which serve as an alternative to glucose as a source of energy for the brain.
DR. ARHAN: After we started the ketogenic diet, his seizures has decreased in frequency and severity after just one month, and after six months, the patient’s parents came to me and said he doesn’t have any seizures. And he looks at my eyes as if he’s understanding everything. It was really fantastic.
RAJ: Our patient is now six years old. He can speak in two- or three-word sentences. He hasn’t had a seizure in over a year.
Chapter 3: Diagnosis and Lessons
RAJ: But even though our patient was treated successfully with a ketogenic diet, how did Dr. Arhan eventually reach a diagnosis?
She walks us through her thinking.
DR. ARHAN: You have to think about Doose syndrome in patients with developmental and epileptic and encephalopathy who are previously normal. After the seizure starts, if there is a cognitive impairment, cognitive regression, language plateau or something like that, you have to think about a few differential diagnoses. And Doose syndrome is one of these differential diagnoses.
RAJ: Syndromes are like constellations of stars… as the sun sets and night falls, stars start to appear… a few here, a few there…After a while, we recognize entire constellations: where stars were once random, they’ve now formed patterns…
And as Dr. Arhan mentioned, normal early development, followed by the onset of drug-resistant seizures and language regression are three bright stars that show up in many constellations – or syndromes – of epilepsy.
DR. ARHAN: This means the drug-resistant epilepsy seizure associated with developmental regression, this leads us to the diagnosis of Doose syndrome.
RAJ: Dr. Arhan came to her diagnosis by combining patient history, clinical observations and test results.
DR. ARHAN: But, in Doose syndrome the patients are mostly normal before the age of two. They don’t have febrile seizures, and by combining the clinical results, EEG and MRI, I came to the decision.
RAJ: But there are still so many unanswered questions – what causes Doose Syndrome being the biggest one… There’s no one defining symptom of Doose Syndrome.
This case is a good reminder that we don’t necessarily need to know exactly what we’re treating to be able to treat it effectively.
There are still so many unknowns when it comes to understanding the causes of rare diseases.
It’s a race against time too. Waiting to arrive at a precise diagnosis before prescribing treatment can be a death sentence for some patients.
DR. ARHAN: If you treat the patient as early as you can, the prognosis might be normal. They may develop normal after the treatments. You may achieve complete remission and these patients may develop normal. One other thing is that please think about a ketogenic diet in the first treatment approach in these patients without losing any time.
RAJ: Treating patients early buys both the patient and the family time, which can potentially save a life.
The world of rare paediatric diseases is developing rapidly… there’s no telling what precise causes, and hopefully treatments, might be discovered in the future…
Hopefully, with early treatment, we can give our patients a chance to experience all that future can offer.
RAJ: Thanks to Dr Arhan for speaking with us.
This is DDx, a podcast by Figure 1.
Figure 1 is an app that lets doctors share clinical images and knowledge about difficult to diagnose cases.
I’m Dr. Raj Bhardwaj, host and story editor of DDx.
You can follow me on Twitter at Raj BhardwajMD.
Head over to figure one dot com slash ddx, where you can find full show notes, photos and speaker bios.
This season of DDx is sponsored by BioMarin Pharmaceutical Inc.
This podcast is intended for healthcare professionals only.
For more information on diagnostic testing go to paediatricseizures.com
Thanks for listening.