DEE-SWAS (Night Terrors, Sleep EEG Abnormalities etc.) masquerading as Regressive Autism

  

 

One of the key points in understanding "autism" is that it is not a single biological condition. It is just a behavioral diagnosis based on observed developmental patterns involving language, social communication, repetitive behaviors and sensory differences.

That means very different biological conditions can produce children/adults who all outwardly appear some version of “autistic.”

A striking example of this was recently shared with me by one of our readers.

 

A Child Diagnosed with "autism"

The parents noted severe developmental regression accompanied by unusual sleep disturbances and night terrors. Over time they also observed something very interesting, that changes in valproic acid (VPA) dosing appeared to significantly affect symptoms.

Their neurologist had performed EEGs which reportedly showed abnormalities and yet despite this, no further major investigations were ordered:

• no epilepsy-protocol MRI
• no prolonged 24-hour EEG
• and no comprehensive workup for epileptic encephalopathy.

Meanwhile, the family pursued extensive genetic testing searching for answers.

This is unfortunately an increasingly familiar story in developmental medicine, a child receives a behavioral autism diagnosis, and the diagnostic process effectively stops there.

 

Seeking a second opinion

The family eventually attended a specialized pediatric neurology clinic at a major children’s hospital.

The difference was immediate.

After reviewing EEGs, videos before regression, videos after regression and recordings of the child’s sleep terrors, the specialists concluded that the child fit the modern framework of:

DEE-SWAS
(Developmental and Epileptic Encephalopathy with Spike-and-Wave Activation in Sleep)

The older terms for overlapping conditions include:

• ESES (Electrical Status Epilepticus in Sleep)
• CSWS (Continuous Spike-Wave During Sleep)
• Landau-Kleffner syndrome

The clinic immediately ordered:

• epilepsy-protocol MRI
• prolonged 24-hour EEG
• metabolic investigations
• ophthalmologic evaluation
• orthopedic assessment

Most strikingly, they reportedly stated that this looked like:

“DEE-SWAS masquerading as autism.”

 

What Is DEE-SWAS?

DEE-SWAS is increasingly understood as a disorder of abnormal brain network synchronization during sleep.

The key issue is not simply seizures. Some children have obvious seizures, others do not.

In many children, pathological spike-wave activity during deep non-REM sleep may interfere with:

• language development
• memory consolidation
• emotional regulation
• cognition
• attention
• and developmental plasticity itself.

Some primarily present with:

• regression
• loss of speech
• autistic behaviors
• sensory abnormalities
• emotional dysregulation
• fluctuating cognition
• sleep disturbance
• night terrors.

In many cases, the child outwardly appears to have classic regressive autism.

 

Why night terrors matter

Night terrors are usually benign in ordinary children.

However, in the context of

• developmental regression
• abnormal EEGs
• fluctuating cognition
• or epileptiform activity

they become much more significant.

DEE-SWAS specifically affects deep slow-wave sleep — the same sleep stage associated with night terrors and abnormal arousal phenomena.

This does not mean every child with night terrors has epileptic encephalopathy.

But regression plus unusual sleep phenomena should raise suspicion that a prolonged sleep EEG may be warranted.

 

Treating the EEG to treat the child

One of the most interesting concepts in modern DEE-SWAS research is:

“Treating the EEG to treat the patient.”

The concern is that the abnormal sleep spike-wave activity itself may drive the developmental deterioration.

Treatments used include:

• valproic acid
• clobazam
• clonazepam
• steroids
• ketogenic diet
• acetazolamide (Diamox)
• ethosuximide
• and in some cases surgery.

Ethosuximide is particularly interesting because it is a T-type calcium channel blocker that affects thalamocortical spike-wave synchronization.

The thalamus appears to play a major role in generating these pathological sleep oscillations.

Ketogenic therapies and ketone esters are also fascinating because they may:

• stabilize neuronal metabolism
• reduce hyperexcitability
• alter glutamate/GABA balance
• and improve network stability during sleep.

 

For more information on treatment:

Treatment of Developmental/Epileptic Encephalopathy With Spike-Wave Activation in Sleep

Is DEE-SWAS Rare?

Officially, yes. But many experts suspect it is significantly under-recognized.

Why? Because many children with:

• regression
• autism
• language loss
• or sleep problems

never receive a prolonged sleep EEG monitoring.

A short daytime EEG may miss much of the pathology.

This is especially important because some children may improve substantially when the abnormal sleep-related epileptiform activity is treated.

DEE-SWAS is likely a spectrum from mild to severe. The underlying cause varies, but often is thought to be an anomaly in an ion channel (calcium, sodium, potassium).  

Autism is just a behavioral phenotype

Cases like this reinforce an increasingly important idea.

“Autism” represents a common behavioral phenotype arising from many different biological mechanisms.

For one child:

• synaptic dysfunction may dominate.

For another:

• mitochondrial dysfunction.

For another:

• immune dysregulation.

And for another:

• sleep-activated epileptiform encephalopathy.

The behavioral presentation may look similar, while the biology underneath is profoundly different. The treatment will also be different, although there are surprising overlaps.

 

Conclusion

DEE-SWAS is not just a case of a bad night’s sleep.

The concern is months or years of abnormal electrical activity repeatedly disrupting the brain during one of its most critical developmental states.

In DEE-SWAS the brain spends large portions of deep sleep in a pathological synchronized firing mode instead of normal developmental processing.

Over time this may interfere with language acquisition, cognition, emotional regulation and developmental plasticity itself, potentially leading to developmental regression and a child who outwardly appears to have regressive autism.

This post is not suggesting that most regressive autism is actually DEE-SWAS, but some clearly is.

However, children with:

• clear regression
• fluctuating abilities
• sleep deterioration
• night terrors
• language loss
• episodic worsening
• or unusual EEG findings

deserve more extensive neurological investigation than they often receive.

The father who contacted me persisted despite initial dismissal and eventually reached a centre experienced in developmental epileptic encephalopathies.

That persistence may prove extremely important for their child’s future outcome.

New insights into myelination reviewed through the What, When and Where autism framework

 

A new paper was recently published by researchers at the City University of New York (CUNY) may have implications far beyond myelin disorders such as multiple sclerosis. The study demonstrated that glucose is not merely a fuel source for the developing brain, but also acts as a developmental signal controlling myelin formation.

We know that myelination can be delayed, or just impaired, in many types of autism.

Modern imaging increasingly suggests that some neurodevelopmental disorders involve altered developmental timing of white matter maturation, rather than structural defects.

That fits very well with:

• delayed milestones
• asynchronous development
• regression windows
• partial catch-up trajectories

 

The technology available includes:

Conventional MRI — shows gross white matter and myelination patterns; useful for detecting delayed myelination, hypomyelination, or structural white matter abnormalities.

Diffusion Tensor Imaging (DTI) — advanced MRI technique measuring white matter connectivity and tract integrity indirectly through water diffusion.

Advanced myelin imaging (MTI, Myelin Water Imaging, MRS) — more specialized scans that estimate myelin content or metabolic function related to myelin and brain energy use.

 

Researchers Discover a New Link Between Brain Sugar Levels and Myelin Development

https://www.gc.cuny.edu/news/researchers-discover-new-link-between-brain-sugar-levels-and-myelin-development

 

Oligodendrocytes make myelin, and you need a lot of them.

An oligodendrocyte progenitor cell (OPC) is an immature brain cell that can divide and later mature into an oligodendrocyte, the cell responsible for producing myelin around nerve fibers.

The paper showed that high local glucose levels stimulated oligodendrocyte progenitor cells to divide and increase their numbers rather than mature immediately into myelin-producing cells.

While lower glucose states and alternative fuels such as ketone bodies supported maturation into myelin-producing oligodendrocytes. Importantly, when glucose-derived acetyl-CoA production was impaired, oligodendrocytes were still able to mature and eventually produce myelin by switching to ketone-derived metabolic pathways.

In essence:

·        Glucose was especially important for expanding the number of OPCs.

·        Ketones can support later oligodendrocyte maturation and myelin production when glucose pathways were impaired.

·        Ketones cannot replace glucose

·        Ketones can augment a glucose deficient brain

 

While the study focused on myelination, it may also provide a useful framework for thinking about autism and neurodevelopmental disorders.

One conceptual model I use to understand autism is what I call the “3W framework”, or the What When and Where of autism:

• What dysfunction?
• Where in the brain?
• When during development?

This new research fits remarkably well within this framework.

 

WHAT dysfunction?

Autism is unlikely to represent one single biological abnormality. Two autistic individuals may share behavioral features while having very different underlying neurobiology.

Potential dysfunctions may include:

• Synaptic dysfunction
• Mitochondrial abnormalities
• Redox dysregulation
• Neuroinflammation
• ER stress
• Myelination abnormalities
• Developmental timing abnormalities
• Excitation/inhibition imbalance

This new paper introduces another important candidate dysfunction -
metabolic regulation of oligodendrocyte development and myelination.

The important insight is that metabolism itself appears to regulate developmental state transitions.

The study showed that glucose-derived acetyl-CoA regulates histone acetylation and developmental gene expression in OPCs. In other words, metabolism is not simply supplying energy to the brain. It is helping instruct cells when to proliferate and when to mature.

This is a major conceptual shift.

In autism research, metabolism has traditionally been viewed mainly through the lens of energy deficiency or mitochondrial dysfunction. However, this paper supports a newer idea emerging across neuroscience:

Metabolism may act as a developmental signaling system.

This may help explain why some autistic individuals show:

• Delayed rather than absent development
• Uneven cognitive profiles
• Fluctuating developmental trajectories
• Temporary regressions
• Later partial catch-up

These patterns are difficult to explain using static “brain damage” models but fit more naturally with dysregulated developmental timing.

 

WHERE in the brain?

The same dysfunction can produce very different outcomes depending on where it occurs.

Abnormal myelination in:

• Frontal regions may affect executive function and social cognition
• Temporal regions may affect language processing
• Cerebellar circuits may affect sensory prediction and motor timing
• White matter tracts may affect long-range synchronization and processing speed
• Brainstem regions may affect autonomic regulation and arousal

This may explain why autism presents so heterogeneously.

Importantly, systemic treatments are too blunt. Most interventions affect the entire brain simultaneously. A therapy that improves one network may destabilize another.

This may partly explain why:

• Some individuals improve dramatically with metabolic interventions
• Others show little effect
• Some worsen paradoxically

The “Where” dimension is likely critically important but remains difficult to target clinically.

WHEN during development?

This may be the most important insight of all.

The developing brain is not static. Different developmental stages require different metabolic and signaling environments.

The paper demonstrated that:

• High glucose states supported OPC proliferation
• Alternative metabolic fuels supported oligodendrocyte maturation and myelin synthesis

This implies that metabolic requirements change across developmental stages.

That concept may have profound implications for autism.

Many developmental disorders show:

• Delayed milestones
• Asynchronous development
• Developmental plateaus
• Regression windows
• Later partial catch-up

The traditional assumption has often been that cells or circuits are permanently defective.

However, this paper suggests that some neurodevelopmental disorders may involve delayed or dysregulated developmental transitions rather than irreversible failure.

The study is particularly interesting because the mice initially showed reduced myelination but later partially compensated through alternative metabolic pathways involving ketone-derived acetyl-CoA.

This resembles the developmental trajectories seen in many neurodevelopmental disorders, where:

• Development is delayed rather than absent
• Skills may emerge late
• Periods of apparent stagnation may later resolve
• Regression may sometimes reflect failure of compensation during periods of rising developmental demand

This may help explain why some therapies only appear effective during certain developmental windows.

A treatment beneficial during one phase of development may be ineffective or even counterproductive during another.

 

Implications for autism therapies

This paper does not prove that autism is a myelination disorder, nor does it prove that ketogenic therapies are effective for autism.

However, it strengthens several emerging ideas:

• Metabolism may regulate developmental timing
• Myelination may be metabolically sensitive
• Alternative fuels such as ketones may support some developmental processes
• Neurodevelopmental disorders may involve impaired metabolic flexibility
• Therapeutic timing may matter enormously

The future of autism therapy may eventually require understanding:

• What dysfunction is present
• Where it is occurring in the brain
• When during development intervention is most effective

The era of searching for a single universal autism treatment may eventually give way to developmentally timed, biologically targeted interventions tailored to specific neurobiological profiles.

This new myelination research may represent an important step toward that future.

Note that this paper from CUNY does not mention autism, it is just about the myelination process.

 

The use of ketones in autism

A small number of people with autism appear to respond very well to ketone ester supplements. These products are still relatively niche, expensive, and can be difficult to obtain outside the United States. One of the best known examples is KetoneAid KE4.

Ketone esters can produce a substantial and measurable increase in blood levels of the ketone beta-hydroxybutyrate (BHB), often sustained for several hours. This differs significantly from many cheaper “ketone” products, particularly ketone salts, which typically produce much smaller and shorter-lived increases in BHB.

Why some autistic individuals respond positively to ketones remains unclear, but several mechanisms are plausible:

• Alternative brain energy supply
• Improved mitochondrial efficiency
• Reduced glucose dependence
• Changes in redox balance
• Effects on neuronal excitability
• Altered inflammation and signaling pathways
• Possible support for myelination and oligodendrocyte function

The new study showed that oligodendrocyte lineage cells can switch from glucose-derived acetyl-CoA to ketone-derived acetyl-CoA during later stages of myelin formation. This suggests ketones may play a more important developmental and signaling role in the brain than previously appreciated.

Importantly, ketones do not replace glucose entirely. The study demonstrated that glucose signaling remained necessary for oligodendrocyte progenitor cell (OPC) proliferation during early developmental stages, while ketones could support later maturation and myelin synthesis under some conditions.

This may help explain why ketones appear beneficial in some neurological and developmental conditions involving:

• impaired glucose utilization
• mitochondrial dysfunction
• epilepsy
• white matter abnormalities
• metabolic inflexibility

However, responses in autism are highly variable. Some individuals show improvements in:

• alertness
• cognition
• endurance
• behavior
• seizures
• language attempts

while others show little benefit or even worsening.

This variability likely reflects the biological heterogeneity of autism itself. Different individuals may have different underlying dysfunctions involving metabolism, redox balance, mitochondrial function, neuroinflammation, myelination, or neuronal signaling.

At present there is still very little formal clinical research on ketone esters in autism, and most evidence remains anecdotal or exploratory. Nevertheless, the growing understanding of brain metabolism and developmental myelination suggests this may become an increasingly important research area in the future.

Ethosuximide to increase speech in some autism? and PTHS?

I have previously proposed the use of calcium T channel blockers to treat some types of autism. I did suggest that language might be a good target.

Time for T? Targeting language-associated gene Cntnap2 with a T-type calcium channel blocker corrects hyperexcitability driving sensory abnormalities, repetitive behaviors, and other ASD symptoms, but will it improve language? Will it also benefit Pitt Hopkins syndrome (PTHS) and broader autism?

I recently received a question from a reader who read an abstract from a paper presented to the Brain Foundation, that suggested Ethosuximide can increase speech in autism. She also asked what the effective dosage might be.

This subject has come up before in this blog. Ethosuximide is a very specific T channel blocker, commonly used to treat absence seizures. Some readers of this blog have already trialed it. The other interesting one is Zonisamide, which blocks T channels but also has other effects. We have reports that the starting low dose of Zonisamide had some interesting beneficial effects that were lost at the regular higher doses.

I did not expect to find much new information, but that changed when I found the patent document submitted by Charles Niesen. So here is a blog post dedicated to this specific subject.

Here is the full patent:

Method of treating expressive language deficit in autistic humans

Here is an easy-to-read summary:

 

A New Patent Claims an Unusual Approach to Autism Language Deficits

A recent patent proposes a novel pharmacological method for improving expressive language in individuals with autism. Rather than introducing a new drug, the invention repurposes a class of existing anticonvulsant medications—specifically succinimides such as ethosuximide, methsuximide, and phensuximide.

These drugs have long been used to treat epilepsy, particularly absence seizures. However, the patent suggests they may also address one of the most challenging aspects of autism: the inability to initiate and sustain meaningful verbal communication.

 

Understanding the Problem

Autism is often characterized by difficulties in social interaction, but a core feature—especially in more severe cases—is expressive language impairment. Many individuals with autism may speak only in short phrases or single words. Others may respond to questions but rarely initiate conversation or engage in back-and-forth dialogue.

This is distinct from related conditions like Asperger syndrome, where language is typically intact but social communication is impaired. In classic autism, the issue is not just how language is used—but whether it emerges spontaneously at all.

Currently, there are no FDA-approved medications specifically designed to improve expressive language in autism. Most available treatments focus on associated symptoms such as irritability, seizures, or attention deficits.

 

The Core Idea Behind the Patent

The patent proposes that daily administration of a succinimide anticonvulsant—most notably ethosuximide—over an extended period (typically several months) can significantly improve expressive language abilities.

Patients are treated for at least one month, with stronger effects reported after three to six months or longer. The goal is not just increased vocabulary, but a progression toward spontaneous speech and true conversational ability.

 

How Might This Work?

Ethosuximide works by blocking T-type calcium channels in the brain. These channels play a role in regulating neuronal activity and rhythmic signaling.

While the exact mechanism in autism is unknown, the patent speculates that modulating these channels may help normalize communication between brain regions involved in language. Another hypothesis is that the drug may “activate” previously underused or dormant neural circuits.

These ideas remain theoretical and are not yet confirmed by broader research.

 

Dosage and Treatment Approach

The proposed dosing follows standard epilepsy guidelines, typically ranging from 10 to 60 mg per kilogram of body weight per day. In many cases, a range of 20–40 mg/kg/day is used for children, while adolescents and adults may receive fixed doses between 150 mg and 1000 mg twice daily.

Treatment is administered consistently over months, with periodic evaluation of language and behavioral progress.

 

How Speech Was Measured

To evaluate improvement, the patent uses a simple but structured 7-point expressive language scale. This scale attempts to quantify how advanced a person’s spoken communication is, ranging from no speech at all to full conversational ability.

The scale is defined as follows:

• 0 — Nonverbal: No meaningful spoken language
• 1 — Echolalic: Repeats words or phrases (echoing others)
• 2 — Single words: Uses isolated words to communicate
• 3 — Phrases: Combines words into short phrases
• 4 — Sentences: Forms complete, understandable sentences
• 5 — Spontaneous speech: Initiates speech independently
• 6 — Mutual speech: Engages in true back-and-forth conversation

This scale is central to the patent’s claims. Improvements are measured as movement upward along these stages—for example, progressing from single words (2) to phrases (3), or from sentences (4) to spontaneous speech (5).

The inventors argue that even a 1–2 point increase represents a meaningful functional gain in real-world communication.

 

Summary of the Reported Study

The patent describes a small observational study involving 24 patients with autism. Participants were treated with ethosuximide for periods ranging from one month to over six months.

Patients were grouped based on cognitive level, including normal IQ, borderline, mild impairment, and moderate impairment. Language ability was assessed using the 7-point scale described above.

 

Reported Outcomes

Across all groups, improvements in expressive language were observed. The most significant gains occurred in individuals with higher baseline cognitive function.

On average, patients improved by approximately two points on the language scale. This often meant progressing from single words to phrases, or from phrases to full sentences and occasional spontaneous speech.

In some documented cases, children who initially spoke only in isolated words were able to form sentences within six months and engage in basic conversation within a year.

 

Timeline of Improvement

Initial changes were sometimes observed within the first month of treatment. More consistent and substantial gains were reported after three months, with the most pronounced improvements occurring after six months or longer.

Interestingly, the progression of language development in treated patients appeared to mirror typical early childhood language acquisition—albeit delayed.

 

Persistence After Treatment

One of the more striking claims is that improvements persisted even after the medication was discontinued. In several cases, language abilities continued to develop beyond the treatment period.

This suggests the possibility of longer-term changes in neural function, rather than temporary symptom management.

 

Additional Observations

Beyond language, some patients also showed improvements in social interaction and mood. Increased engagement, better eye contact, and reduced irritability were noted in certain cases.

However, many participants were also receiving speech therapy and applied behavioral analysis (ABA), making it difficult to isolate the effects of the medication alone.

 

Safety Profile

Ethosuximide was generally well tolerated in the study. Known side effects include gastrointestinal discomfort, fatigue, and behavioral changes. Rare but serious risks—such as blood or liver abnormalities—are also associated with the drug and require medical supervision.

 

Age Range and Cognitive Profile of Participants

The patent provides limited but useful information about the participants’ ages and cognitive abilities.

Age Range

• The study included both young children and adolescents.
• Specific examples mention children as young as 3 years old and others up to around 12–15 years old.

Cognitive (IQ) Groups

Participants were divided into four categories based on cognitive level:

• Normal IQ (NIQ)
• Borderline IQ (BIQ)
• Mild intellectual impairment (mMR)
• Moderate intellectual impairment (moMR)

 

Key Takeaways

• The strongest language improvements were reported in children with normal IQ.
• Children with lower cognitive levels also improved, but to a lesser degree.
• The results suggest that baseline cognitive ability may influence response to treatment.

 

Final Thoughts

This patent presents an intriguing hypothesis: that a well-established epilepsy medication may have the potential to improve core language deficits in autism.

The reported results are promising, particularly the magnitude of language gains and their persistence after treatment. However, the evidence is limited by the small sample size, lack of a control group, and reliance on a subjective rating scale.

As it stands, this work should be viewed as exploratory rather than definitive. Larger, controlled clinical trials would be needed to determine whether this approach truly offers a reliable and reproducible benefit.

Still, the idea highlights an important direction for future research—targeting the underlying neural mechanisms of communication itself, rather than just managing associated symptoms.

 

Critical periods and CNTNAP2

Another factor to consider is the role of developmental “critical periods,” when brain circuits involved in language are particularly plastic. Disruption of CNTNAP2 has been linked to altered neuronal connectivity and delayed circuit maturation, which may extend or shift these windows of plasticity. If so, interventions that stabilize network activity—such as T-type calcium channel modulation—might help enable more effective language development during these periods. This could potentially explain why some improvements, once initiated, continue even after treatment is stopped.

This also raises the possibility that timing may be critical. If language development depends on sensitive developmental windows, and pathways involving CNTNAP2 alter the timing of circuit maturation, then the age at which a treatment is given could determine its effectiveness. Interventions such as T-type calcium channel modulation may be more beneficial when applied during periods of higher neural plasticity, and less effective once circuits have become more established. This could help explain why any signal of benefit has been difficult to detect in routine clinical use.

 

Conclusion

The study did not have a placebo group. We know from many previous small studies that in most cases everyone improved in autism studies, including those who were assigned the placebo.

Has Niesen identified a simple therapy that will improve speech in autism?

If ethosuximide strongly improves language, why has this not already been noticed?

Neurologists have used ethosuximide for decades for autistic children with absence seizures, but it is not widely recognized as a language-enhancing drug.

I expect there likely is a subgroup of responders, but it will not be a silver bullet for all.

Ethosuximide is cheap, but it can have some unusual side effects.

Zonisamide is more predictable than Ethosuximide, but still can have problematic side effects, more so than drugs like bumetanide or atorvastatin.

It may be the case that responders to Ethosuximide do not need to take it permanently and that has to be factored into the side effect assessment.

Any potential benefit is likely limited to a specific subgroup, such as children with subtle absence seizures, epileptiform activity, or abnormalities in calcium channel signaling. One candidate subgroup involves mutations in the CNTNAP2 gene, which are associated with language impairment, autism, and increased neuronal excitability. Preclinical studies suggest that targeting T-type calcium channels in such models can reduce hyperexcitability and improve behavioral features, raising the possibility that drugs like ethosuximide may be more effective in individuals with similar underlying biology.

CNTNAP2 is also regulated by TCF4, the gene mutated in Pitt-Hopkins syndrome, a condition marked by profound speech deficits. This points to overlapping biological pathways underlying language impairment across different neurodevelopmental disorders and reinforces the idea that identifying responders will be key to determining clinical value.

So, another idea for Pitt Hopkins parents is to consider is Ethosuximide. Maybe the parents’ organisation should contact Charles Niesen to make a small clinical trial, like the forthcoming Clemastine one.