Roo's Clues

This blog is a way of sharing the information and resources that have helped me to recover my son Roo from an Autism Spectrum Disorder. What I have learned is to view our symptoms as the results of underlying biological cause, which can be identified and healed. I say "our symptoms" because I also have a neuro-immune disorder called Myalgic Encephalomyelitis.

And, of course, I am not a doctor (although I have been known to impersonate one while doing imaginative play with my son)- this is just our story and information that has been helpful or interesting to us. I hope it is helpful and interesting to you!

Monday, June 8, 2026

Landau-Kleffner Syndrome and Autism

From NORD (National Organization for Rare Disorders):
- Landau Kleffner syndrome (LKS) is a rare childhood disorder characterized by the loss of language comprehension (auditory verbal agnosia) and verbal expression (aphasia) in association with severely abnormal electroencephalographic (EEG) findings during sleep and clinical seizures in most patients.
- symptoms typically begin between the ages of three and seven years although the condition may rarely occur in children as young as 18 months of age.
- A significant minority of children with LKS also develops serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors but rarely the severe social impairments seen in autism spectrum disorders.
- The cause of Landau-Kleffner syndrome is unknown although a spectrum of epileptic conditions including LKS has been described in individuals with GRIN2A gene mutations and other candidate genes including RELN, BSN, EPHB2 and NID2 have been suggested.
- The response in some patients to immunosuppression has raised the question of autoimmune and other inflammatory mechanisms as potential contributors.
- In additional to language regression, the diagnosis requires the presence of severely epileptiform activity on EEG, particularly during non-REM sleep. Additional testing may include magnetoencephalography. Brain imaging with magnetic resonance imaging (MRI) is recommended to exclude structural lesions since several cases have resulted from brain tumors. Other testing including behavioral and/or brainstem evoked audiometry and standardized psychometric and speech/language testing are helpful to exclude hearing loss and provide the basis for therapies to aide in recovery.
- The standard therapeutic approach begins with antiepileptic drugs, particularly “spike-suppressing” medications such as divalproex, ethosuximide, levitiracetam, and benzodiazepines. Some authors have suggested using a combination of corticosteroids and pulse benzodiazepines. Other antiepileptic drugs that may be beneficial are lamotrigine and felbamate.
- When antiepileptic drugs are ineffective, other approaches include the ketogenic diet or treatment with intravenous immunoglobulin. Calcium-channel blocking drugs may also be beneficial. A neurosurgical procedure called multiple subpial transection (MST) has been used in some centers for children who fail to improve linguistically within two years and for those who develop steroid dependency or toxicity.

From Child Neurology Foundation:
- Symptoms include Verbal Agnosia (difficulty repeating words, reading, writing), Auditory Agnosia (unable to understand or recognize sounds), and seizures (about 75% of children with LKS will have at least one seizure), abnormal EEG (findings may include electrical status epilepticus in sleep (ESES)), hypersensitivity to sounds, behavior problems (attention and inhibition problems, hyperactivity, aggressive behaviors, social withdrawal), and psychiatric problems (anxiety, depression, problems controlling emotions).
- Treatments include steroids (can improve EEG findings, language problems, behavior problems), benzodiazepines (can improve EEG and language problems), IVIG, anti-seizure medication, SSRIs (can help with anxiety and behavior issues), speech therapy, and educational intervention.
- The severity of language problems can vary for people with LKS. Some children may regain full function of their language skills with treatment (over months to years). Others may not.

Basic information about Landau-Kleffner Syndrome (LKS) that was found in this paper:
- (LKS) is a rare childhood neurological condition that causes developmental regression, loss of language skills and abnormal electroencephalogram (EEG) patterns.
- Several studies have found that an arginine to histidine mutation at site 518 in the GRIN2A gene is highly correlated with LKS and other epilepsy-aphasia syndromes [2].
- Boys are more likely to be affected and the syndrome is associated with partial penetrance and autosomal dominant pattern of inheritance.
- At the time of onset, a child will present with symptoms of auditory verbal agnosia. Seizures are noted in 75%-80% of the cases with cognitive impairment, memory disorders, and global regression in behavior, as well as hyperactivity.
- Electroencephalogram (EEG) findings in patients showed regional spikes in the fronto-, centro-, or posterior-temporal areas of the brain in all patients. Other characteristic EEG findings include continuous and diffuse slow spikes and waves, mostly at 1.5-2.5 Hz, immediately after the patient falls asleep. These patterns continue through all the slow wave-sleep stages [3].
- Treatment for LKS has included anti-epileptic drugs (AED) with corticosteroids. Studies show that the use of AEDs alone does not improve the aphasia. Valproate has been used to prevent seizures. Sulthiame and clobazam have helped with the aphasia [1].
- the paper includes a case study of a child with LKS who was treated with "cortexin, nootropics, hopantenic acid, magnesium, B6, Sonopax (thioridazine), and glycine." The authors speculate this this patient's LKS may have been triggered by a tick bite.

From MedicineNet "symptoms of LKS appear later in childhood and do not include social difficulties." (when compared to ASD).

From Autism Research Institute:
- These individuals first lose their ability to comprehend (i.e., receptive speech) and then their ability to speak (i.e., expressive speech). These changes can occur gradually or suddenly.
- People with Landau-Kleffner Syndrome have abnormal EEG patterns (i.e., brain waves) in the temporal lobe (located on the sides of the brain) and in the temporo-parieto-occipital regions during sleep.
- Approximately 70% develop epilepsy; and these seizures are typically infrequent and can be either with or without convulsions.
- One common characteristic of Landau-Kleffner Syndrome is the failure to respond to sounds. Thus, parents may suspect their child of hearing loss.
- Autistic characteristics seen in Landau-Kleffner Syndrome individuals include pain insensitivity, aggression, poor eye contact, insistence on sameness, and sleep problems.
- The prognosis is better when the onset is after age 6 and when speech therapy is started early.
- treatments have also been shown to be beneficial for many of these individuals, such as anticonvulsant mediations and corticosteroids. There is also a surgical technique in which the pathways of abnormal electrical brain activity are severed.

Unraveling the Overlap Between Landau-Kleffner Syndrome and Autism Spectrum Disorder: A Systematic Review and Case Series
"Landau-Kleffner Syndrome (LKS) and autism spectrum disorder (ASD) are distinct neurodevelopmental conditions that can present with overlapping features such as language regression, behavioral disturbances, and social withdrawal. These similarities often complicate differential diagnosis, especially in early childhood. Accurate distinction is critical for appropriate intervention and prognosis." The study found that a differential diagnosis between LKS and ASD is complicated and should involve significant observation and multiple specialties, and that the two conditions can also co-occur, increasing the already complex task of diagnosis. It is further emphasized that early diagnosis is important to ensure that the correct interventions are initialed early for best outcome.

Efficacy of ACTH therapy in children with Landau-Kleffner Syndrome and Autism Spectrum Disorder: A retrospective analysis
- Landau-Kleffner Syndrome (LKS) and Autism Spectrum Disorder (ASD), both neurodevelopmental disorders, are frequently associated with epileptic seizures and characteristic epileptiform activity. Electrical Status Epilepticus during Sleep (ESES) is commonly observed in LKS, while Interictal Epileptiform Discharges (IEDs) are typical in ASD.
- Adrenocorticotropic hormone (ACTH) treatment has demonstrated the potential to reduce the indexes of these related discharges and the number of seizures.
- ACTH treatment led to significant improvements in indexes and seizure control in both LKS and ASD populations. In children with LKS and epileptic seizures... 50 % achieving complete seizure control. For children with ASD and epileptic seizures... 41 % achieving complete seizure control. Rare side effects were transient and reversible, with no reports of serious adverse events.

Child with Landau Kleffner Syndrome misdiagnosed as Autism: A case report

Brain Research in Autism

Dr Martha Herbert MD PhD, a pediatric neurologist at the Center of Morphometric Analysis, Massachusetts General Hospital, wrote a piece that summed up one of the underlying schisms in the research community that explains a lot of the chaos in the brain research community regarding autism as well as why making sense of this research is the source of many disagreements:

"The positions in the parallel sets of debates tend to cluster into two provisional models, each of which links clinical and research data into a different gestalt. One model sees autism as a strongly genetic brain-based disorder, with a constant prevalence but a recent increase in awareness that has led to the appearance—but not the reality—of an epidemic. The other model sees autism as a genetically influenced but environmentally modulated condition involving multiple systems of the body, with increased numbers being real and related to changes in environmental factors."

Basically, the disagreement is whether autism is the RESULT of abnormalities in the brain, or whether abnormalities found in the brain are CLUES to a deeper underlying cause that was probably triggered by environmental factors. If you believe that abnormalities in the brain cause autism, then it makes sense to fish around until you find the abnormalities and then simply identify the genes responsible. As Dr Herbert so eloquently points out in the above article, this approach has not really lead anywhere. If you view abnormalities in the brain as the result of deeper, underlying causes- if you view autism as a disorder that affects the brain, as Dr Herbert says, rather than one that is of the brain, finding abnormalities in the brain leads to the conclusion that autism is a whole-body, multi-system disorder. While there is a component of genetic involvement, it is not in a deterministic way- a saying that you hear over and over in the biomedical world is that "genes load the gun, the environment pulls the trigger". The above article by Dr Herbert is a good introduction to the basics of the biology of autism, including increased oxidative stress, widespread inflammation (including neuroinflammation), impaired mitochondrial function, impaired detoxification ability, and impaired cellular metabolism.

Autism: a Brain Disorder, or a Disorder that Affects the Brain? by Martha Herbert
Clinical Neuropsychiatry (2005) 2, 6, 354-379
In this paper, Dr Herbert discusses the ideas presented in the article linked to above in much greater detail. Additionally, she discusses some of the brain research more specifically and flushes out the implications of the different models in regards to interpretation of the results.

So, keeping in mind that brain research in autism is most useful as one piece of a much larger puzzle, here are some studies that provide some insight. Studies that find involvement of one or more particular brain region:

Stanford Scientists Successfully Reverse Autism Symptoms in Mice
"Overactivity in the reticular thalamic nucleus was shown to cause autism-like behaviors in mice. Drugs that reduce this activity reversed the symptoms."

Left-hemispheric atypicalities in the primary auditory cortex are associated with language comprehension and social skills in children with Autism Spectrum Disorder
"First, the results revealed a reduction of M200 and altered M200 sensory gating effect in the left auditory cortex in children with ASD. Second, these alterations were related to lower language comprehension skills and higher autistic symptom severity. Finally, altered MEG responses were associated with gray matter thickness reduction as well as abnormal gyrification in the primary auditory cortex in ASD. The study revealed low-level functional and structural atypicalities in children with ASD and their relation to clinical phenotype."

Studies suggesting abnormalities in cortical development:

Sunday, June 7, 2026

Nutrition Information

(see also General Supplement Notes)

General Sources of Nutritional Information

Physicians Committee for Responsible Medicine. Nutrition Guide for Clinicians. (multiple chapters)
Micronutrients in Health and Disease
Celiac Disease

USDA What's in Food and FoodData Central

USDA Dietary Guidance

USDA Nutritional Evidence Systematic Reviews

National Academy of Medicine Dietary Intake Requirements (basically RDAs)
There are many listings here, some for general topics such as energy requirements and some for groups of specific nutrients.

Linus Pauling Institute Micronutrient Information Center

Immune Function and Micronutrient Requirements Change over the Life Course

Nourishing Hope (Site for Julie Matthews, a nutritionist who specializes in using nutrition to heal health conditions, particularly neurological ones such as autism, ADHD, anxiety, OCD, etc).

Plant-Based Diets
It is very important when eating a plant-based diet to be mindful about getting adequate nutrition. The following resources can help. This is not an endorsement of plant-based eating, I am passing along important information regarding this diet.

Nutritional Assessment of the Symptomatic Patient on a Plant-Based Diet: Seven Key Questions
This paper focuses on seven significant nutrients that must be carefully planned for when eating a plant-based diet. These are: vitamin B12, iron, EFAs, calcium, zinc, and vitamin D, and complete proteins. The paper includes a list of additional resources regarding nutrition and a plant-based diet including:

Physicians Committee for Responsible Medicine. Good Nutrition.

Dr. Greg Plotnikoff on Dysautonomia/MCAS

Notes from an episode of The POTSCAST/Mast Cell Matters:
(this link includes a transcript of the interview down the page)

This episode features Dr Plotnikoff, a highly respected doctor and researcher in the areas of chronic pain and related conditions. For more on Dr Plotnikoff or to follow him go here:
Minnesota Personalized Medicine
on Instagram

He and colleagues are well-known for their foundational contribution to understanding the contribution of vitamin D deficiency to chronic pain conditions. His work on this subject includes:
Prevalence of severe hypovitaminosis D in patients with persistent, nonspecific musculoskeletal pain
"All patients with persistent, nonspecific musculoskeletal pain are at high risk for the consequences of unrecognized and untreated severe hypovitaminosis D. This risk extends to those considered at low risk for vitamin D deficiency: non-elderly, non-housebound, or non-immigrant persons of either sex. Non-immigrant women of childbearing age with such pain appear to be at greatest risk for misdiagnosis or delayed diagnosis. Because osteomalacia is a known cause of persistent, nonspecific musculoskeletal pain, screening all outpatients with such pain for hypovitaminosis D should be standard practice in clinical care."

Vitamin D Deficiency as a Contributor to Multiple Forms of Chronic Pain: In Response
In this follow-up comment, Dr Plotnikoff references the work of others that has identified various unusual pain syndromes involving symptoms such as excessive pain in the skin that is sensitive to bright lights and even light pressure, and that resolves with vitamin D normalization, as well as patients wth bone pain that was resolved with vitamin D supplementation. He encourages readers to further research vitamin D deficiency on Pubmed as there are many new discoveries in this area.

The interview begins with Dr Plotnikoff discussing research findings that he learned about at the most recent Dysautonomia International conference, including a a presentation by Dr. Chip Norris at Medical University of South Carolina (and his lab, which includes many researchers who have hEDS themselves) that found that in a cohort of patients with hEDS, the average number of comorbidities was 25. The most common was pain, the second most common was Dysautonomia, and the third was GI concerns. Dr Dempsey asks if this may be because so many people with hEDS also have MCAS. He also references research by this lab that hasn't been published yet that took a deep look at the genetics involved in hEDS and what they found was surprising- unlike other forms of EDS that have a clear genetic basis in collagen and connective tissue genes, hEDS instead has to do with genes involved in auto-inflammatory states and pathways.

This shifts the focus onto the category of auto-inflammatory syndromes. Dr Dempsey remarks that she and Dr Afrin have found that "a fair number" of their MCAS patients have been found on genetic testing (in vitae or whole genome sequencing) to have auto-inflammatory conditions including NOD2 as well as other, more rare mutations, and that at this point it is unclear whether these genetic factors are drivers of MCAS, predictors of it, or something else.

A new category of auto-inflammatory disease associated with NOD2 gene mutations

Discussion now jumps to a presentation by Tae Chung from Johns Hopkins concerning the genetics involved in Long COVID. He found multiple pathways that were abnormal, including TCN2. Dr Dempsey then relates these findings to a study by Brigham and Women's Long COVID and Chronic Fatigue Syndrome Clinic that also looked at proteomics (the study of proteins) and found 3 that were exceptionally elevated including one protein involved in B12 transport. When considering B12 levels you would also want to know the methylmalonic acid and homocysteine levels. B12 is important for the central nervous system so a problem with a transporter could have significant effects and could explain why many patients seem to require high doses of B12 delivered intramuscularly.

Discussion jumps again to an article in Nature about CoQ10 deficiency. Researchers studied a child with a genetic cause of CoQ10 deficiency and were able to identify which step in which process was not functioning properly. They were then able to treat the child with a synthetic form of whatever the next step in the pathway is and the child regained the ability to walk.

Discussion now jumps to talk of an approach to treating gastroparesis, slow motility, nausea and vomiting, that is used in Japan were they give IV thiamin and pantothenic acid. Thiamin deficiency is sometimes called Beriberi and in America is thought to be essentially non-existent outside of severe cases of alcoholism and malnutrition. The symptoms include Anorexia, nausea, abdominal pain, vomiting, early satiety, low motility, constipation, and eventually parasthesias. There is recent evidence now of a "gastrc Beriberi" from a case study published by Harvard recently. (Thiamine deficiency can be mistaken for MS). Dr Dempsey notes that she has seen low levels of thiamine and riboflavin in many of her patients. She also notes that gluten-free diets are low in thiamine. Baking anything over around 250 degrees causes the thiamine to break down. Baking soda also breaks it down. Washing rice washes it out. It is also destroyed by UV light so clear packaging allows it to break down.

Most importantly, mycotoxins break down thiamine (in particular fumonisins - 30 species of fumonisins are potent thiamin breakers as well as at least one mycotoxin from penicillin). Thiamine contains a fragile methyl bridge so is easily broken down. These mycotoxins can come from molds that grow directly on the grain or are involved in its storage, but can also come from mold in a living environment. There are also organisms in the microbiome that destroy thiamine including bacillus subtilis, candida, H. pylori, and Staph aureus. Some medications destroy thiamine including omeprazole, antibiotics, metformin and diuretics (which can flush thiamine out of the body). Multivitamins tend to contain the forms thiamin hydrochloride or thiamin mononitrate which have very low levels of absorption (around 3% to 5%). The RDA of thiamine for people on feeding tubes or TPN is much higher. Magnesium is necessary to activate thiamine.

Blood tests are not a good measure of the body's thiamine levels because less than 1% of the body's thiamine is in the blood. the rest is on cells, especially red blood cells. "people with Wernicke's encephalopathy have demonstrated normal thiamin levels". Other markers that can indicate low thiamine levels include high pyruvate, "high phytanic acid to pristanic acid ratios or high branch chain fatty acids or high branch chain amino acids. The sister keto acids, isovaleric, et cetera are all decent measures." "And there are 11 different places where thiamin acts in the body, three of them directly related to the Krebs cycle, and including upstream from GABA, the calming neurotransmitter."

Vitamin B1 deficiency in patients with postural tachycardia syndrome (POTS) This paper by Svetlana Blitshteyn found evidence of thiamine deficiency in POTS patients, although didn't take into account the limitations of blood testing. Thiamine is necessary for the body to make acetyl-CoA, which in turn is necessary to make acetylcholine, which is the neurotransmitter of the autonomic nervous system. Thiamine also augments the function of acetylcholine and helps to support acetylcholine levels.

Best ways to supplement thiamine? Thiamin hydrochloride and thiamin mononitrate are both not well absorbed so should not be relied upon. Myers Cocktail, an IV boost of nutrition contains a good dose of thiamine as well as the magnesium needed for it to be used. Allium vegetables are some of the best food sources (onions, garlic, leeks). Allimax is a garlic based supplement that has been helpful for some.

Allithiamin which is a type of thiamin commercially available that can be combined with lipoic acid as Lipothiamin.

Benfotiamine is a fat-soluble form of thiamine that is well absorbed. It has shown some benefit in Alzheimer's patients in several small, randomized trials. Dosing is either 300mg once or twice a day.

Riboflavin (B2) is a mast cell stabilizer and it helps migraines. Dr Plotnikoff discusses the potential nutritional deficiencies that they and other doctors are seeing in some patients on plant-based diets. They specifically mention riboflavin, vitamin B12, and long chain Omega-3 fatty acids. The following paper was published by them to discuss these specific concerns:

Nutritional Assessment of the Symptomatic Patient on a Plant-Based Diet: Seven Key Questions

Additional commentary about nutrition on a gluten-free plant-based diet "gluten-free plant-based diet has no methionine in it, as does Orgain plant-based kind of protein drinks or Kate Farms 1.4 or multiple other plant-based protein, you know, kind of shake type supplements. No methionine. No methionine means no methylation. No methylation means things related to, you know, neurotransmitter production, mood, memory, energy, sleep, estrogen clearance, histamine clearance all depends upon this."

Thursday, January 29, 2026

FOXP3 and Autoimmunity

The 2025 Nobel Prize in Medicine has been awarded for one of the most important discoveries in immunology: the biological system that keeps your immune system from turning on you.

Your immune cells are trained to destroy viruses, bacteria, and other foreign invaders. But that power has to be kept in check – or it can misfire, attacking your own organs. The process that prevents this is called peripheral immune tolerance, and it’s largely controlled by a type of cell called the regulatory T cell.

This year’s Nobel went to Mary E. Brunkow, Fred Ramsdell, and Shimon Sakaguchi for uncovering the genetic and cellular systems that make this immune self-regulation possible.

Back in 1995, Sakaguchi identified a previously unknown class of T cells that seemed to hold back the immune system from attacking the body. A few years later, Brunkow and Ramsdell discovered the gene that controlled them – FOXP3 – after studying a rare, fatal autoimmune disease in children. They found that when this gene is mutated, the immune system becomes unregulated and begins destroying healthy tissue.

Two years after that, Sakaguchi made the connection: FOXP3 was the master switch for the same immune-regulating cells he had identified earlier.

These discoveries launched a new field of research. Regulatory T cells are now being investigated in therapies to suppress autoimmunity, improve transplant success, and even enhance cancer treatment by modulating immune suppression around tumors.

Saturday, September 27, 2025

Acetominophen Use and Autism- The Evidence

Using acetaminophen during pregnancy may increase children’s autism and ADHD risk

Mount Sinai Study Supports Evidence That Prenatal Acetaminophen Use May Be Linked to Increased Risk of Autism and ADHD

Evaluation of the evidence on acetaminophen use and neurodevelopmental disorders using the Navigation Guide methodology

FDA memo to physicians Notice to Physicians on the Use of Acetaminophen During Pregnancy

Tylenol is a brand name for the drug acetaminophen, which is the last of a class of drugs still on the market that were derived from coal tar. It was put on the market when it's predecessor, phenacetin, was taken off the market due to being highly carcinogenic. The other drug from the class, acetanilide, was withdrawn from the market because it was found to be hepatotoxic (toxic to the liver) and caused methamaglobinemia (blocking the ability of hemoglobin to carry oxygen).

Tylenol & Autism: The Peripartum Risk We’re Missing with Dr. William Parker

Thursday, September 25, 2025

Mast Cell Involvement in Other Diseases and Disorders

Mast cell involvement in other diseases and disorders"

In general:

A list of illnesses and conditions linked to Mast Cell Disease from the MCAS Mast Cell Activation website

Mast Cell Activation Disease and methylation
Mast Cells are Important Modifiers of Autoimmune Disease: With so Much Evidence, Why is There Still Controversy?
Mast cells and adrenal function
Mast cells: an expanding pathophysiological role from allergy to other disorders
Mast Cell Involvement in the Pathogenesis of Selected Musculoskeletal Diseases

Mast Cells in Liver Disease Progression

Mast cells in the brain and psychiatric effects:
(see the post Mast Cells, MCAS, and Psychiatric Symptoms)

In autism:
Mast cell activation and autism
Neuro-inflammation, blood-brain barrier, seizures and autism