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of children with LKS also develops serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors but rarely the severe social impairments seen in autism spectrum disorders.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 

 

 

 

Mitochondria and Mental Health

Brain Energy, Mitochondria, and Mental Health
Dr Chris Palmer, MD, Harvard Psychiatrist

A major change in psychiatry has been going on for awhile now in which more and more clinicians and researchers are recognizing mental health disorders as related to, and sometimes caused by, physical states in the body and therefore using therapies that are meant to address these states.  A primary example of this is looking at brain metabolism (mitochondrial function in the brain).

The Keto diet is a 100 year old, evidence based therapy that can stop seizures that medication can't stop.  This is evidence of how powerful nutrition and diet can be in treating and altering brain function.  Psychiatrists use epilepsy medications to treat people with other mental mental health conditions often, usually off-label, so there's nothing new about using the ketogenic diet to treat other mental health conditions.  Seizure meds are used to treat dementia, eating disorders, anxiety, psychosis, mood disorders, substance use disorders, and others.  

The Brain Energy Theory- Mitochondria do more than just produce energy for cells "mitochondria play a role in directing and allocating resources for cells".  Not all of the food that mitochondria in the brain process is turned into ATP- some is turned into serotonin, dopamine, or cortisol, and they also play a part in regulating those molecules.  Mitochondrial function is one way of understanding the imbalances of the neurotransmitters and hormones in the brain.  They are also involved in regulating inflammation (turning it both on and off) and epigenetics by signaling the nucleus of the cell to regulate the transcription of gene.  They monitor our outer and inner environment; sensing stress levels, food intake, blood sugar levels, and oxygen levels.  

"Mitochondria play a role in our response to trauma- psychological and social stressors."  Trauma and stressors play a role in mental illness, so this connection could be very significant, because while people have known that there is a connection they haven't known exactly what that connection is on a biological level.  He points out that mitochondria seem to be a way to "connect the dots" in the mental health puzzle between factors like trauma, neurotransmitters, sleep, substances like drugs and alcohol (I would add exercise and sunlight too).  These are all things that affect mitochondrial and metabolic health or are affected by it or both.  People with mental health conditions have higher rates of many physical disorders including diabetes, obesity, heart attacks, strokes, and generally have a shorter life expectancy.  This connection also opens up the possibility of more and better treatments.

For people who struggle to believe this connection is real, he explains that mitochondria are what drives metabolism, which is how we take food and oxygen and transform them to keep ourselves alive.  If these processes are disturbed it means illness, and if they are disturbed enough or stop, we die.  Most poisons work by harming mitochondria- that's how they harm or kill you.  Other cellular components can be harmed without nearly as much danger to the organism.  It makes sense that since mitochondria are the most important part of the cell and what keeps it able to perform its function, if they aren't functioning right the cell won't be able to function right.  

Mitochondria can become both under-active AND overactive.  This makes sense because there are mental health disorders involving areas of the brain becoming overactive as well as areas becoming under-active.  If the health of mitochondria impacting the cell's functioning is the cause or major contributing factor to many mental health disorders that would explain why they can be better or worse at different times of day (or different seasons), why they can be worsened by stress and sleep deprivation.  A lot of the details aren't known yet but already the basic insight that mitochondria are central to mental health is transformative of the fields of psychiatry and psychology.

What options are available to support mitochondrial functioning?

There are a huge variety of things available to help mito function including sun exposure, red light therapy, various supplements, glutathione, methylene blue, and more, but these can only help so much if core lifestyle issues aren't addressed.  For example, alcohol is a potent mito toxin so a person drinking a large amount daily is poisoning their mitochondria far beyond what those things can help.  Having healthy mitochondria requires lifestyle changes- eating well and avoiding highly processed foods, sleeping well, exercising, and avoiding excess stress.  

The ketogenic diet and its effect on brain function has been studied for a long time, its known to change neurotransmitter levels, inflammation, the gut microbiome, but Dr Palmer says that he believes the impact it has on mitochondria is its most important therapeutic effect.  The keto diet creates a state in the body similar to fasting, which is known to trigger mitophagy (when the cell breaks down old and defective mitochondria that are replaced by new, healthy ones) and mitogenesis (which is the production of new, healthy mitochondria).  Dr Palmer suggests that these two processes that remove old, defective mitochondria and replace them with more and healthier ones, might lead to long-term healing where a person could potentially go off the keto diet and remain healthy.  People who are on the diet to control seizures will usually be kept on the diet for 2 to 5 years after the point at which their seizures completely stop (some people with seizures must stay on keto for life).  People can experience improvement of mental health symptoms, even very significant improvement or remission in weeks or months.  Psychotic symptoms tend to take weeks if not months to improve especially if severe.  People often wonder if making some changes in their diet, such as eating more fatty fish, will be enough.  Dr Palmer says maybe for people with relatively mild symptoms or conditions, some changes such as eating more fatty fish can help, but he points out that those changes don't stop seizures but the keto diet does, he says  "ketogenic therapy is a unique and powerful intervention".

What about other interventions to support mito health?

Exercise is a really important factor also and should be part of a treatment plan.  The two types of exercise for which there is the most evidence of benefit for mito health are strength training (aka lifting weights, working out to build muscle) and level 2 cardio (which he defines as 3-60 minutes of running, cycling, etc that gets you breathing hard but not out of breath).  Those types of exercise increase the number and health of mitochondria in muscles which then send endocrine signals to your brain that improve brain function.  Exercise alone isn't enough to heal mito, lose weight, or heal type 2 diabetes.  If people exercise more but don't change how they eat they don't get significant or sustained weight loss.  There has been one very well-done study of middle-aged adults who were prescribed exercise.  In addition, half were given the drug metformin to take and the other half were given a placebo.  The group that got metformin didn't get the mito and metabolic benefits of exercise the way the other group did, which is evidence that metformin interferes somehow with mitochondrial biogenesis.  Many other medications, including many psych meds, are known to interfere in mito function and biogenesis, so this should be considered.  Lifestyle behaviors such as drinking alcohol and smoking cigarettes and marijuana are also mito toxins.  

The psych drugs that can do this are mostly the anti-psychotics, which have been known to have metabolic side-effects and neurological side effects.  They can cause significant weight gain (he has seen people gain as much as 100 pounds in 6 months), they can cause type 2 diabetes, they worsen every known risk factor for cardiovascular disease (raise blood pressure, raise triglycerides, worsen LDL levels), and increase inflammatory biomarkers.  

This represents a new way to understand mental illness and what might be happening in the brain, and a new way to treat it.  This is especially important as mental health remains highly stigmatized in the US and research around it receives very little funding in comparison to disorders considered to be physical.  Many mentally ill people are in prisons, shelters, or even on the street.  "There is tremendous injustice, in my mind, in how we treat people with mental illness".  Dr Palmer points out that while psychological and social factors play a role in mental illness, it's no less physical and "real" in that way.  People with mental illness "deserve medically necessary treatment".  If we can get needed care to people in prison or who are homeless and who have mental illness, they won't be in prison or homeless anymore, they can live enjoyable, productive lives. 

 

 

 

 

 

 

Carbon Monoxide Brain Injury

Carbon monoxide is an invisible odorless gas that is a byproduct of burning fuels including auto emissions, lawnmowers, fireplaces, furnaces and other natural gas appliances such as water heaters.  Natural sources include forest fires and a small amount from the breakdown of heme in the body.  Smoking increases CO levels and smokers have increased CO levels to between 5% and 9%, but heavy smokers can have levels up to 15% in the blood.  In the indoor environment, smokers become net contributors to ambient CO levels.  CO can build up in the air inside and reach dangerous levels if there is not proper ventilation or the burning is occurring in a small, confined space.  

Some lesser-known sources of CO include "incomplete combustion and inadequate ventilation of domestic natural gas, indoor burning of charcoal for barbecues, propane gas cylinders (forklift trucks), petrol powered generators, and methylene chloride exposure from spray paint (hepatic conversion to CO)".  Carbon monoxide monitors can be placed near potential sources to alert you if there is a leak.  Many travel experts recommend bringing a carbon monoxide monitor with you when you travel because regulations vary from place to place and are not always fully enforced anyway.

"COHB decreases with a half life of approximately 320 minutes in air. However this half life is further decreased to 80 minutes if 100% oxygen is given to the patient."  Symptoms of carbon monoxide poisoning include headache, dizziness, fatigue, poor tolerance for exercise, weakness, chest pain (also called angina), nausea, vomiting, and confusion.  Acute exposure can lead to confusion, seizure, loss of consciousness, and even death.  The presence of additional stressors, such as low temperatures may increase the effects of CO.  A number of studies have found even small changes in ambient CO levels correlating with cardiac complications and death "levels of CO commonly found in urban outdoor air may induce arrhythmia, angina, and sudden death in people with heart disease." as well as a statistically significant increase in Myocardial Infarction in patients with increased chronic exposure to CO.    

"To make the diagnosis, a blood test with access to a co-oximeter, to measure carboxyhaemoglobin (COHB) levels is required." If a person survives the exposure they may have long-term damage to the brain.  The symptoms of brain injury from carbon monoxide resemble those of brain injury from other sources and can include headaches, dizziness, and difficulties with sleep, mood, balance, vision, movement, memory, and other cognitive problems.  Symptoms may be present right away or can be delayed.  Injury to the brain from acute exposure can often be seen on MRI scans soon after the exposure occurred.

Carbon monoxide exposure can lead to brain injury in several ways.  It can cause hypoxia, a state in which the brain does not receive adequate levels of oxygen, because carbon monoxide binds to the hemoglobin in the bloodstream which limits the amount of oxygen that can be transported to the cells in the brain.  If cells don't receive enough oxygen they are not able to produce enough energy to function properly and can even die, particularly in the brain region called the hippocampus which is important for memory.  Carbon monoxide can also cause injury to the brain from inflammation, from damaging certain proteins that surround neurons, and from causing iron to be released into the brain which is toxic to brain cells.  In some cases, treatment with Hyperbaric Oxygen Therapy can reverse some of this damage.

Carbon Monoxide Brain Injury

Carbon monoxide poisoning mimicking gastroenteritis

Association of the frequency of acute cardiorespiratory complaints with ambient levels of carbon monoxide

Revenge of the barbecue grill. Carbon monoxide poisoning

Occult carbon monoxide poisoning in patients with neurologic illness
"We conclude that unrecognized carbon monoxide poisoning occurs in a small but important fraction of patients with wintertime neurologic illness and can be identified by a characteristic risk factor profile."

Chronic and occult carbon monoxide poisoning: we don’t know what we’re missing
"There is a strong possibility that low level exposure to CO is responsible for widespread and significant morbidity, however the clinical syndrome produced is often overlooked because of a range of presentations, obscure symptoms, and a lack of awareness of the problem.  In the USA, comparatively small changes in ambient levels of CO as a result of pollution have been shown to affect rates of presentation to emergency departments with various complaints."

"“Occult CO poisoning” is used to indicate those cases of CO poisoning that may never come to the attention of a medical practitioner. In most cases, this is as a result of chronic CO poisoning and most frequently the patient will not even ask for a medical opinion. Occasionally acute poisoning as a result of exposure to high concentrations of gas may remain occult, and although the patient presents to a medical practitioner—the diagnosis is missed (at least until the patient re-attends, often with cohabitees with similar symptoms). Occasionally, deaths have occurred."

"Pyramid of disease: CO poisoning can be looked upon as a “disease” with a pyramid of presentation—the tip of the iceberg is overt acute poisoning, while the base is occult, low level exposure. A difficult question to answer is: how big is the base? Even ambient levels of CO in the atmosphere as a result of pollution cause changes in the hospitalization and mortality rates of patients with certain diseases."

"At levels of COHB greater than 10% patients with pre-existing cardiac disease experience increased severity and duration of angina and if levels rise above 15% they are at increased risk of myocardial infarction. If a patient has had an acute myocardial infarction, the threshold for ventricular fibrillation can be reduced to 9% COHB.  Patients with severe chronic bronchitis or emphysema experience a significant reduction in the walking distance when breathing air after exposure to CO and intermittent claudication occurs with less provocation in patients with low levels of COHB. Even in normal subjects a COHB concentration as little as 4.4% has been shown to limit work capacity and maximal oxygen consumption." 

"In patients with acute poisoning, 30% or more may experience delayed onset of neuropsychiatric symptoms. Symptoms include cognitive and personality changes, dementia, psychosis, parkinsonism, amnesia, depression, and incontinence. There is also good evidence that apparently minor low level acute and chronic exposure causes varying degrees of neuropsychological impairment.  It is postulated that CO causes lipid peroxidation of neurological tissues.  Early hyperbaric oxygen therapy decreases the extent of lipid peroxidation and this would explain the decreased incidence of neuropsychiatric sequelae after hyperbaric treatment. The regions of the brain most frequently involved include the globus pallidus and deep white matter.

Epidemiological bases for the current ambient carbon monoxide standards

Ambient carbon monoxide and increased risk of daily hospital outpatient visits for respiratory diseases in Dongguan, China

Systematic review and meta-analysis of studies between short-term exposure to ambient carbon monoxide and non-accidental, cardiovascular, and respiratory mortality in China
"Our meta-analysis demonstrated that exposure to ambient CO was positive with risk of deaths from all non-accidental causes, total cardiovascular, and respiratory diseases. Based on these findings, tougher intervention policies and initiatives to reduce the health effects of CO exposure should be established."

Chronic and occult carbon monoxide poisoning: we don’t know what we’re missing

Carbon monoxide poisoning mimicking gastroenteritis.

Carbon monoxide: not gone, not to be forgotten

Stress (Cortisol and Adrenaline)

The inside of the adrenal glands is neurological tissue, which is where adrenaline is made.  The outer part is glandular tissue and is where cortisol is made.  Cortisol is a hormone and adrenaline is a neurotransmitter.  The adrenals release these chemicals in order to help the body to function in situations of short-term stress, but can remain active for a long time.  They are part of the sympathetic nervous system, which is also known as the "fight or flight" system.  The opposing branch of the autonomic nervous system is the parasympathetic response, which is a state of relaxation.  The adrenal glands are not part of the parasympathetic system so that system is unable to "turn them off".  Fear, worry, and anxiety are part of the sympathetic response.  

The Effects of Stress

Stress causes problems with sleeping, often resulting in waking during the night (often around 2 AM) and can mean that a person sleeps best in the morning rather than at night.  Cardiovascular effects include changes in blood pressure and heart rate, and inflammation of the arteries.  Cortisol is an anti-inflammatory hormone. The synthetic version is called prednisone.  Long term cortisol exposure leads to loss of sensitivity by the cortisol receptors on cells, similar to how insulin resistance happens in diabetes.  With cortisol resistance, more cortisol may actually increase inflammatory symptoms in a seemingly paradoxical way.  Diseases that can develop in this situation include arthritis, auto-immune diseases, and joint inflammation.

The Effects of Cortisol on the Immune System

Cortisol affects the white blood cells of the immune system because part of what it does is to "turn off" the immune system.  Cortisol inactivates Natural Killer T-cells, which kills viruses and cancer cells.  It also suppresses the ability of the immune system to fight pathogens in general.  There are even certain bacteria that activate your hypothalamus to activate cortisol so that your body can't defend itself as well.  

Cortisol and Memory

In the short term, cortisol helps in the formation of emotional memories because these memories may help you to survive in the future, but in the long term the hippocampus is damaged, leading to memory loss and brain fog.  This can also result in becoming per-occupied with a few specific problems, which can lead to keeping you awake at night because you can't turn off the worries.  You can get stuck in a problem-solving mindset but it doesn't result in actual helpful solutions.  

Mineral Loss

Long-term exposure to cortisol leads to the loss of potassium, which is a mineral that supports calmness and relaxation.  Loss of potassium leads to more stress and this can create a cycle.  Sugar also depletes potassium.  Thiamine (vitamin B1) is an important anti-stress vitamin that causes relaxation and comfort. Thiamine also increases levels of GABA, which is a neurotransmitter of relaxation and calmness.  It also causes a loss of hydrogen ions, which are acidic, which puts your body into a more alkaline state.  People under a lot of chronic stress become too alkaline, not too acidic.  This leads to tight muscles, twitches, tetany. muscle cramps, can't absorb electrolytes well, and breathing problems can result.  As the acid levels decrease this can cause low levels of stomach acid and poor digestion.  

Catabolic Effect

Catabolism is the process in which muscles are broken down in order to turn the amino acids, the components that muscle proteins are made of, into glucose to fuel the "fight or flight".  Connective tissues including collagen and elastin are also broken down in this process (this is why stress can make a person wrinkly).  Cortisol also demineralizes bone, causing osteopenia and osteoporosis.  

Effect on Kidney Function

Chronically high cortisol levels cause the kidneys to filter less (meaning hold on to less and instead allow more to be lost in the urine), including minerals such as potassium.  Sodium is filtered and saved and this is why kidney problems can lead to water retention.  Addison's Disease is a rare and more serious form of adrenal disease in which potassium is filtered but sodium is lost in the urine.  Cushing Syndrome is related.  

Cortisol and Blood Sugar

Cortisol is also called a "glucocorticoid" because it helps to regulate glucose levels.  It can help make glucose out of non-carbohydrate sources including fats, proteins, and even ketones. It also plays a role in storing and releasing glucose.  Cortisol can activate insulin leading to a "flat tire" around the gut, and this also leads to all the issues associated with high insulin.  

Cortisol and Digestion

The process of digestion is under the control of the parasympathetic system, and becomes compromised when cortisol levels remain elevated.  The digestive system becomes sluggish resulting in bloating, indigestion, poor absorption of nutrients, and even ulcers.  The fact that cortisol also increases insulin levels this can also affect digestion and cause excess belly fat.  

Excess cortisol can lead to low levels of vitamin D which is ironic as vitamin D does many of the same things that cortisol does, but without the negative side effects.  It is an anti-inflammatory and can influence the immune system to lower inflammation rates, in particular it tamps down the cytokine storm.  

How to Lower Stress and Reduce Cortisol

It can lower mental stress to find activities that increase physical stress such as jobs around the house, yard work, etc.  These activities result in a kind of physical tiredness that can improve sleep.  Exercise and other types of physical activity can also be helpful.  Worry and stress are associated with inaction, feeling almost paralyzed, and keeping busy with activities helps keep you moving and keeps your mind from getting stuck on certain topics.  Taking vitamin B1 is very helpful at cutting stress down.  It can have an almost immediate effect if taken when you feel very stressed.  Making sure that you get enough potassium and magnesium is important and both are easily gotten from the diet, especially vegetables.  Reducing carbohydrate intake helps because carbs keep the body stuck in a "fight or flight" response.  Taking vitamin D lowers stress and improves mood.  Implementing a ketogenic diet and intermittent fasting helps to address a lot of the physical symptoms and mood symptoms from high cortisol.  Including adaptogens in your daily routine, as a supplement or tea or other ways, supports healthy adrenal function.  

Learning to breathe so that the inbreath and the outbreath are the same duration helps balance the sympathetic and parasympathetic arms of the autonomic nervous system.  If you practice this when you lay down to go to bed it will help you sleep.  Below is the link to a video made by Dr Berg showing a technique to reduce stress at the end of the day, using a thing that puts pressure on the base of the skull.

Dr.Berg's Webinar On Stress Relieving: Easily Get Rid of Stress & Sleep Like a Baby

This is an adaptogen supplement recommended by Dr Berg

Growth Hormone

Growth hormone is sort-of opposite of cortisol, it protects proteins.  It’s anti-aging whereas cortisol is pro aging.  GH is triggered by sleep,  intense but intermittent exercise, eating enough protein, and intermittent fasting. 

Homeopathic Remedies

Homeopathy is used along with biomedical treatments quite often.  In my personal experience, and in watching and hearing about the experiences of others, it seems to be quite successful for some people and not helpful at all for others.  Also, despite claims that homeopathy can never have side effects or do harm, I do know of at least 2 cases in which homeopathic treatment to clear viruses caused a significant and long term worsening of mitochondrial disease and possibly other conditions.  My own family gave it a good try early on in Roo's medical journey and while we had some successes the gains were not reliable enough to justify the ongoing cost and effort at the time (we were paying some of his travel expenses in addition to the fees for the appointments).  

We have recently been trying again with certain remedies and are getting very good results for some things and reasonable gains with others.  The homeopath that we were seeing when Roo was younger was John Melnychuk who is amazing and one of the more knowledgeable homeopaths in treating autism and the many other symptoms and conditions which commonly occur in people with ASD and their families.  I do highly recommend him.  Although we are once again dabbling in homeopathy I am not very knowledgeable about it so am only posting some basic information.

For some more general info about homeopathy I have this post.

General Sources of Information for Choosing a Remedy:

Boiron Medicine Finder 

German Apotheke information on remedies

PeaceHealth Health Information Library (searchable for homeopathic remedies)

HomeopathyPlus (Know Your Remedies)

Boericke's Manual of Homeopathic Materia Medica (online searchable version)

National Center for Homeopathy

Interhomeopathy

Homeopathica

Learn a more advanced method for selecting a remedy

 

Dosing- which potency should I use?

Specific Uses of Homeopathics:

Homeopathic remedies for radiation and radiological procedures (such as x-rays, CT scans)

Homeopathic vaccination

Homeopathy and Autism

Where to get remedies:

Washington homeopathic (huge selection, lactose in pills)

Hahhneman homeopathic

Helios Homeopathy

Homeopathic Family Medicine

HomeopathyPlus

Some of the most common and useful remedies for the types of symptoms and health challenges faced by people like me and my family:

Aconite Napellus - sudden onset anxiety and panic, fear, croup, ear infections.

Apis Mellifica (bee sting) - allergy symptoms including anaphylaxis (not to be substituted for epinephrine in anaphylactic shock, but may help while waiting for ambulance), such as redness, swelling, burning, stinging.  Restless, clumsy, light sensitivity.  General inflammation.

Argentum Nitricum - anxiety, OCD (compulsions and "harming thoughts"), gassiness and distended belly, conjunctivitis, hoarseness, and exhaustion.

Arnica Montana - pain and soft tissue injury, concussion, healing from surgery or dental work.

Aurum Metallicum (gold) - Depression with suicidal thoughts, hopelessness, self-criticism and self-loathing, sense of life as a burden and not worth the effort.

Belladonna - sudden onset fever, migraine, sensitivity to light, motion, or pressure; dizziness, sunstroke, insomnia (even though sleepy), swollen glands, high blood pressure.

Chamomilla - oversensitivity to pain, irritability and anger, teething pain or toothache, colic in infants.

Cina - anti-parasitic, abdominal complaints and poor digestion, sensory and emotional sensitivity, anemia, coughing and other throat problems including difficulty swallowing and choking on liquid,

Coffea Cruda (coffee) - insomnia, PTSD, feeling jittery and restless.

Gelsemium- anxiety, weakness and trembling, fatigue and exhaustion, headache, dizziness.

Histaminem (histamine) - allergy symptoms from hay fever, food allergies, insect stings/bites, etc.

Hypericum Perforatum (St John's Wort) - often called "the arnica of the nerves".  For sharp, shooting, hot pain after injury, often with spasms (indicated in particular by "hot pain").  Pain from head trauma, pain in eyes and/or ears, especially if sadness or other mental changes, from shock, especially if on right side of head.  Radiating neuralgic pain and/or numbness, often sudden onset, worse with weather changes.  Can also treat emotional injuries and pain, depression, anxiety.

Ignatia - PTSD (with frustration and hopelessness), depression with recent onset.

Nitricum Acidum (nitric acid) - headaches, sound and light sensitivities, very sensitive and prone to reactions, weakness and trembling, muscle twitches, associated with mercury poisoning, cracked skin, sharp splinter-like pains, diarrhea, sensitive to cold, anemia and wasting in advanced disease states, bleed easily, weak and pitted bones.

Magnesium Phoshphorica - menstrual pain and cramps

Nux Vomica (poison nut tree, contains strychnine) - symptoms from over-indulgence (food, alcohol, coffee, etc.), digestive and emotional symptoms, hernia, migraine, asthma, nausea, fatigue/exhaustion, influenza, urinary tract infections (with frequent need to pee), constipation, kidney stones, gallbladder inflammation, hepatitis, hay fever, and sensitive to light, sound, and odors.

Phosphorous - asthma, bronchitis, pneumonia, tightness in chest, dry lingering coughs, deep coughs, general fatigue, weakness, irritability. Helps clotting post-surgery and with nosebleeds, bleeding gums, heavy menstrual flow.

Phytolacca Decandra - swollen glands such as lymph nodes and tonsils, heat and soreness from inflammation, reduces scar tissue and fibroids.  Helps with skin conditions associated with internal infections.

Pulsatilla Nigricans - (meadow anemone aka windflower) - tends to be for women, changeable and unpredictable but also dogmatic, paradoxical in many ways, bottles up emotions, weepy, tends towards anxiety and depression, fearful.  Kindness and sympathy help but also bring on tearfulness.

Rhus Tox - back pain (esp. with stiffness), arthritis, joint pain, Cervical Spondylosis (degeneration of vertebra in the neck), hernia (from weight lifting), hives (from exposure to cold)

Sepia Succus (ink from cuttlefish) - menstrual pain and symptoms, sensitivity to cold, hives (triggered by cold exposure), miscarriage, endometriosis, long term depression with indifference.

Sol - sunburn

Sulfur - hives (triggered by heat), general skin itching.

HOMEOPATHIC NOSODES:

So far these notes are all in regard to classical homeopathy.  There are several other forms of homeopathic treatment, one of which is the use of homeopathic nosodes.  Nosodes are remedies made from diseased tissue itself or from the pathogen directly and are used when the symptoms being treated began during or following a specific illness such as influenza or Epstein-Barr Virus.

BY SYMPTOM/CONDITION:

Homeopathic remedies for asthma (Antimonium Tartaricum, Arsenicum Album, Grindelia, Kali Bichromicum, Nux Vomica, Phosphorous, Pulsatilla Pratensis)

Homeopathics for anxiety (list includes Aconite Napellus, Argentum Nitricum, Arsenicum Album, Calcarea Carbonica, Gelsemium Sempervirens, Kali Arsenicosum, Kali Phosphoricum, Lycopodium Clavatum, Phosphorous)

Remedies for Panic Attacks and High Anxiety from WAPF
Also- Natrum carbonicum (insecurity with social situations; fear/panic in unfamiliar surroundings),

Top 5 remedies for depression (includes Ignatia, Natrum Mur, Aurum Met, Sepia, Kali phos)

Remedies for Chronic Fatigue Syndrome (Gelsemium, Kali phosphoricum, Mercurius solubilis, Phosphoric acid and other “acid” remedies, Scutellaria, Zincum metallicum)

Remedies for fatigue, exhaustion, sleepiness (Kali phos, arsenicum album, nux vomica, phosphoricum acidum, picricum acidum, silicea, and zincum metallicum)

Homeopathy for menstrual pain and other symptoms (list includes Lachesis, Belladonna, Cactus grandifolia, Chamomilla, Cimicifuga, Colocynthis, Magnesia phosphorica, Nux Vomica)

Also - Phosphorous (heavy menstrual flow), Sepia (menstrual problems, irregular cycles, dysmenorrhea, morning sickness, uterus prolapsed, not well since menopause)

Remedies for hernia (list includes nux vomica, calcarea carbonica, lycopodium clavatum, rhus tox, silicea)

Remedies for post-surgery - Arnica (helps bruised and damaged tissue heal), Hypericum (reduces pain, speeds healing, and prevents infections), and Opium (this addresses the side effects of the anesthesia used)

Allergy symptoms - Apis, Euphrasia Officialis (itchy, watery eyes), Histaminem, Kreosotum (itchy skin, eczema, psoriasis, edema), Natrum Muriaticum, Phosphorous (asthma), Rhus Tox, Sepia, Sulfur

Migraine - Cyclamen (beginning with visual disturbances/aura), Glonoinum (with head congestion), Iris Versicolor (with intense vomiting, nausea, or heartburn), Kali Phosphoricum (from stress), Natrum Carbonicum (from sun exposure), Natrum Muriaticum (occuring during menstruation), Bryonia (pain begins over left eye, constipation), Belladonna (pain worsens with movement, light, and pressure, rapid onset),

Digestive problems - Lycopodium (liver problems, indigestion with burping, dyspepsia, biliousness, flatulence, bloated abdomen, baby's colic), Phosphorous (nausea, empty cold feeling, heartburn, flatulent colic, ulcers).  See also Indigestion and Gas

Osteoporosis and broken bones - Silicea, Symphytum, Arnica, Bryonia Alba (back pain), Calcarea carbonica, Calcarea phosphorica (promotes bone growth), Hypericum Perforatum (back pain),

Pain - Hypericum perforatum (shooting nerve pain, or from puncture or crushing wounds), Magnesium Phosphorica (cramping, muscle spasms), Oreodaphne Californicum (neuralgic headache. cervical-occipital pain, cerebrospinal meningitis), Rhus Tox (arthritis, joint pain, lower back pain)

PTSD - Opium, Kali Phosphoricum (with night terrors), Aconite Napellus (after sudden event or shock), Coffea Cruda (with trouble sleeping due to active mind)

Radiation exposure (from medical testing for example) - Cadmium Sulphuricum, Homeopathic X-ray

Meditation, Mindfulness, and Breath Work

There has been more and more awareness of the damage that chronic stress can do to our bodies, even having epigenetic effects.  Chronic stress in childhood is especially toxic but the chronic stress that the parents of many special needs kids, especially children with autism and/or serious health conditions experience, is also very harmful.  Then on top of all of that there is the added stress of dealing with medical insurance companies, doctor's offices, the intense financial demands that chronic health issues place on a family, and the school system if you choose to send your child to school.  Having as many tools as possible to help us calm our anxiety, sleep better, stay more focused and present, and to minimize the effects of an intrinsically stressful life, becomes a necessity.  Since I am homebound, what works for me the best are guided visualizations and meditations.  There are so many different approaches and styles, so I am including a few of the shorter ones here as a sort-of sample pack so that you can try some different approaches.  I have also found that some of these guided meditations are truly wonderful in helping me fall asleep.

Adorable Animated Mice Explain Meditation in 2 Minutes

Why Mindfulness Is a Superpower: An Animation

Why Meditate? | Change your Brain's Default ModeThis video is an excellent introduction to meditation- what it is, why it helps, and how it changes our minds (both our physical brains as well as our functioning minds).

A Buddhist monk shares his perspective on meditation to keep it simple and effective

Mindfulness Guided Meditation - 5 Minutes

How to Meditate - 5 Minute Meditation Escape (this video demonstrates a particular method)

Buddhist Monk shares his Secrets of Meditation

WORKING WITH CHAKRAS

Before Sleep | Beginners Spoken Guided Meditation | Chakra Alignment |How to Chakra Balance




Activating the hand chakras

The Science Of Yogic Breathing | Sundar Balasubramanian

The speaker found that after practicing yogic breathing regularly, he began to produce more saliva.  Not only would this be helpful for people with chronic dry mouth, but also saliva has many different contents in addition to being a digestive fluid.  It also has hormones, proteins, growth factors, including nerve growth factor.  Nerve Growth Factor not only helps nerve cells to grow but it is protective of nerve cells and helps them live longer.  Levels of nerve growth factor are significantly reduced in people with Alzheimer's.  Nerve Growth Factor is given therapeutically to patients with Alzheimer's so he did a clinical trial which showed that yogic breathing does raise levels of nerve growth factor.  They also found other proteins and hormones that are involved in coping with stress and pain, cancer, immune function, and other things.  There is a saying when talking about meditation that the mind is a monkey- but not just a normal, a drunken monkey who has been stung by a scorpion.  Because of this trying to control the mind is very hard.  Instead, we can focus on controlling our breath, which then helps to tame the money.

Breath -- five minutes can change your life | Stacey Schuerman

If you only have a few minutes there are some simple (and not "woo-y") exercises you can do to address stress, shown here.

More Sleep Notes

These are my notes from several of the lectures in the series called Secrets of Sleep Science: From Dreams to Disorders, which is a recording of a class on sleep taught at Stanford University by Professor H. Craig Heller, PhD, and available from The Great Courses series.  I have also posted my notes for other lectures in the series including:

The Neuroanatomy and Neurochemistry of Sleep

The Neurophysiology of Sleep

Narcolepsy

The Function of Sleep

The primary function of the insulin system is to maintain a steady blood glucose supply to the brain.  The brain does not need insulin in order to take up sugar from the blood the way other body cells do, so by turning insulin on and off the body can allocate energy to the nervous system.  When a muscle or body part needs more fuel it can increase blood flow to that area, but this takes time.  In the meantime muscles and tissues have reserves of energy which can exist as fat or as glycogen.  A glycogen molecule is a long branched chain of glucose molecules.  In the brain glycogen is made and stored in cells called glia.  The two primary types of cells in the brain are neurons and glia, and there are about 9 glia for each neuron (this is where the erroneous myth that we only use 10% of our brains comes form).  The hypothesis for this lecture is that the function of sleep is to restore the glycogen reserves in the brain.  This idea is supported by the fact that a buildup of adenosine leads to sleep, and adenosine builds up as energy is depleted.  Adenosine opens potassium channels.  The injection of a chemical that mimics adenosine into the brain of animals causes them to go into deep slow-wave sleep.

Glycogen breakdown, known as glycogenolysis, is done by an enzyme called glycogen phosphorylase.  Glycogen is made by glycogen synthase.  The neurochemicals that promote wakefulness activate the glycogen breakdown enzyme, and inhibit the glycogen synthesis enzyme.  When the levels of these neurochemicals goes down at the onset of sleep, glycogen synthase is activated and the glycogen breakdown enzyme is inhibited.  ATP inhibits the glycogen breakdown enzyme.  Experiments found that sleep deprivation caused the most decrease in glycogen levels in the cortex, and the least in the brain stem.  Areas of the brain that work harder, sleep harder; also supporting the idea that sleep has the function of restoring depleted energy reserves.  Glia cells provide energy from glycogen to neurons in the form of lactate.

The Timing and Function of REM Sleep

The first part of the night is dominated by non-REM sleep, and the second half of the night sees more REM sleep.  All mammals show cycling between non-REM and REM sleep.  Is it possible that wakefulness creates the need for non-REM sleep, and non-REM sleep creates the need for REM sleep somehow?  In studies of sleep deprivation, non-REM sleep comes first still, except in some extreme cases of total sleep deprivation, in which sleep-onset REM (SOREM) is seen.  When rats are deprived of all sleep, serious failures of major physiological systems occurs.  In studies that attempt to deprive the rats of only REM sleep, those same failures occur, just more slowly.  The selectively REM-deprived rats became much more aggressive (possible sign of hallucinations?).  Since REM deprivation has a significant impact on the quality of non-REM sleep, studies that attempt to study only REM deprivation must be viewed as studies of total sleep disruption.

Is there a homeostatic relationship between non-REM and REM sleep, that explains why they cycle?  REM need builds up during non-REM sleep, as it builds up it is more likely to interrupt non-REM sleep (could the dysfunctional REM sleep onsets in narcolepsy be driven by an unmet need for REM sleep at night?).  Human sleep studies also show that the length of REM sleep episodes corresponds to the length of the preceding non-REM sleep period, which supports the homeostatic model in humans well.

What about SOREM, or sleep-onset REM?  This occurs in people who are very sleep deprived, such as those with sleep apnea or narcolepsy.  Two possible explanations are that people with excessive daytime sleepiness tend to nap, and that high-density EEGs show that episodes of slow-wave sleep occur in regions of their brains during wakefulness.  So maybe REM sleep need is building up in people who are having non-REM sleep processes during their awake phases.  Obstructive Apnea events are more likely to occur during REM than non-REM sleep, which means that these people will have an accumulating REM need that is not being met.

How could non-REM sleep create a need for REM sleep?  What does REM sleep do for non-REM sleep processes?  Non-REM sleep is characterized by slow waves, which result from hyper-polarization of the neurons, which results from the leakage of potassium ions.  The membrane potential is more negative during non-REM sleep than it is during REM sleep.  The composition of the extra cellular fluids, where the potassium builds up, is controlled bu the glial cells.  The glia take up the excess potassium ions from the extra cellular fluid- is it possible that REM sleep is when these potassium ions are moved back into the neurons?  In a study that limited the leaking of potassium from neurons during non-REM sleep, it was found that REM sleep was eliminated.  When the drug wore off REM sleep returned but there was no rebound effect which suggests that the drug was not simply masking the need for REM sleep but actually eliminating it.   Interestingly, the drug used was apamine, which is in honeybee stings, and which blocks potassium channels, which depolarizes the neurons, making them more sensitive and more likely ton fire.  (So, could narcolepsy be caused by an inability to regulate potassium ions in the brain?).

Insomnia

Sleep state misperception is when someone has brain activity that is such that they think that they are awake when they are actually asleep.

Sleep Apnea

Sleep apnea is the partial or complete lack of breathing during sleep.  In central sleep apnea, the part of the brain that controls breathing takes a break, so the lack of breathing is not accompanied by an effort to breathe.  Central sleep apnea is thought to be one possible cause of SIDS.  The other kind is called Obstructive Sleep Apnea, which is when the person is trying to breath but the breathing is blocked.  The person will awaken just enough to breath, which is very disruptive to sleep patterns through the night.  It is said to be like watching someone choke.  The person with sleep apnea does not remember these awakenings and is not aware that this is happening.  Obstructive sleep apnea occurs when the soft tissues of the throat collapse during sleep.  This is more likely to happen in cases of obesity or certain facial structures.  People with small lower jaws or receding chins are much more likely to develop sleep apnea (what about connective tissue disorders such as Ehlers-Danlos Syndrome?).

Parasomnias

REM Sleep Behavioral Disorder is when a person acts out their dreams, it is a temporary loss of the muscle atonia that normally occurs during REM sleep.  The person may be coherent and can injure themselves or others.  Talking and yelling in one's sleep can precede the acting out by years.  This disorder can make someone more likely to develop Parkinson's or Alzheimer's later.

Sleep paralysis usually occurs upon waking, and is when the person is partially awake but still has muscle atonia and may have parts of their dreams still mixed in with their perceptions.  It usually passes in a matter of minutes.

Sleep and the test of the body

Many physiological systems are seriously adversely affected by sleep deprivation, and are restored by sleep.  In rats kept awake, they eventually died after 16-21 days without sleep.  Every physiological system was negatively affected- there were immune system changes, hormonal changes, sores developed on their skin, their fur became oily and matted, they lost weight even as they ate more, and their digestive systems were damaged.  It was like accelerated aging or multi-system failure.  The most striking results in mice studied were their increase in food intake, loss of body mass (especially fat tissue), and even a fall in body temperature.

Human studies have demonstrated large changes in glucose metabolism after 6 days of restricted sleep, enough to give them score of glucose clearance from the blood to put them at risk of type 2 diabetes.  After the subjects were rested, their scores returned to healthy levels.  Epidemiological studies have also found a correlation between short sleep and the development of type 2 diabetes. Other studies suggest that short sleep is strongly correlated with the development of obesity.  Another research study found that after 6 days of restricted sleep, subjects had a significant decrease in a hormone (leptin) that suppresses appetite, and a significant increase in ghrelin, a hormone that increases appetite.  the subjects reported an increase in appetite, especially for carbohydrates.  Sleep loss impairs how the body handles glucose and regulates appetite, and these changes can have lasting effects on metabolism and  body mass.

When we get sick, some of the cells in our immune systems release cytokines that induce sleep.  Even low levels of sleep loss lead to an increased production of pro-inflammatory cytokines.  There is experimental evidence that restricted sleep leads to significantly less antibody formation by the immune system.  In another study, after only one night of limited sleep (limited to 4 hours) subjects' level of natural killer cells in the blood was reduced by 73% (NKC target virus-infected cells and tumor cells).

In experiments with rats, it was found that sleep deprivation led to significant loss of bone density.  This study also found a significant change in the composition of bone marrow.  All bone marrow cells originate from stem cells.  In sleep deprived rats, there was a skewing of the new cells to form blood cells and not to form bone and fat cells.  This increase in blood cells is an inflammatory process.  The amount of each type of white blood cell in the blood is closely regulated.  Diseases of the bone marrow can be treated with a bone marrow transplant.  In a study it was found that bone marrow that was donated form a (mouse) subject (to another mouse) was only half as successful if the donor was sleep deprived the night before the transplant.  Further study showed this to be due to reduced ability of the stem cells in sleep deprived subjects to migrate between the blood and the bone marrow.  Restorative sleep returned the cells' ability to migrate effectively.  It was found that this change was the result of the expression of a single gene that is under the control of growth hormone, a hormone that is released during sleep and suppressed during wakefulness (could this be one cause or contributing factor to Mast Cell Disease, which involves changes in the stem cell production of blood cells?)..

Improving Sleep

OTC sleeping medications almost always have diphenhydramine (benadryl) in them, because histamine is wakefulness promoting.  Melatonin can help to reset the circadian rhythm, if taken at night before attempting to sleep.

Barbiturates and other sedatives  act through the GABA receptor.  This receptor is an ion channel that lets chloride ions into the neuron when it opens.  This makes the membrane potentials of the neurons more negative, and less likely to fire in response to incoming stimuli.  Barbiturates increase the length of time that these ion channels stay open when acted on by GABA, increasing the action of GABA.  They also affect other neurotransmitter receptors as well, in ways that are not well understood and complex.   All benzodiazepines work by binding to a particular site on the GABA receptor. and increase the efficacy of GABA on that receptor. The benzos are more selective than the barbiturates.  Long-term use of these drugs results in tolerance.  Different benzos act on the GABA receptors differently.  Another newer class of drugs, called the Z-drugs because their names begin with the letter Z, act exactly the same way as benzos but are chemically different.  Doxepin works by blocking the wake-promoting effects of histamine, it is a tricyclic antidepressant.  It works better for early morning insomnia.

PTSD results in terrifying nightmares.  It involves over activity in the hippocampus, amygdala, and frontal cortex.  It can be thought of as super consolidation of the memory.  His opinion is that PTSD is a REM sleep disorder, that the nightmares are a major factor in it's development and persistence, and we should be able to treat it through sleep.   His hypothesis is that the nightmares in PTSD are so arousing that the person wakes up, and replays the dream, which allows it to be remembered.  There is a natural amnesia of dreams that often occurs, which he suspects is an adaption to allow us to distinguish between dreams and reality.  People with PTSD have high levels of circulating norepinephrine.