Auditory Processing Disorder

Notes from When the Brain Can't Hear by Terri James Bellis, Ph.D.

Soon after Auditory Processing Disorder was recognized, Dr Jack Katz defined it as "what we do with what we hear".  Auditory processing is everything that happens with sound beyond our ears.  

Common symptoms of an APD include having difficulty understanding speech despite having normal hearing, which can look like asking people to repeat themselves often, having trouble following a conversation, and can be made worse when there is background noise such as a tv or music playing or being in a noisy place like a restaurant.  Sounds in general or speech may sound muffled or distorted, as if the person is underwater, may take longer to comprehend, or certain speech sounds may be missing or hard to distinguish from others.  Some sounds may be indistinguishable. The person's memory for auditory information may be especially poor.  They may also frequently misunderstand people, which can lead to frustration and irritation.  The effort of having to strain to listen can be exhausting and can lead to fatigue and burnout.  So much of the social lives of people involve spoken communication that anything that gets in the way of that can lead to social isolation.  

Chapter One, The Many Faces of APD

-In young children especially, it can look as though they have a hearing impairment or are deaf.  In schoolage children it can make it hard for them to keep up in the classroom, to follow along with the teacher, and to make friends.  

-Having an undiagnosed disorder such as APD can lead a person to conclude that they are stupid and lead to feelings of inadequacy and ignorance, because they don't understand why they struggle and can't do what the people around them seem to do easily or effortlessly.

-APD can cause children to struggle to learn to read and write and keep them functioning at low academic levels and can show up as a noticeable difference between the quality of work the child produces and their abilities with oral language or other abilities.  Specific reading skills that may be impacted include decoding (sounding out words) and auditory discrimination abilities.

-Other signs of APD in children can include speaking out of turn, saying things in conversation that are off-topic, avoiding conversation or speaking in class, difficulty following instructions,  difficulty taking in information presented verbally, 

-A nonverbal child can be taught to do something, such as drop a block into a bucket, to indicate that they have heard a sound.  This is one way of doing a hearing test and is called Conditioned Play Audiometry.  It's very difficult to diagnose a child under the age of about 7 because they must be able to repeat things such as numbers, words, and sentences.   In Auditory Electrophysiology, the way a child's brain responds to sound is recorded by electrodes placed on their scalp.  This is a way to test the central auditory nervous system and create a neural representation of the way the child's brain "hears" sound.

-In addition to the type of APD that affects abilities around speech, which is localized to the left hemisphere, the right hemisphere can be affected by Right Hemisphere Disorder, which has very different symptoms.  Pragmatic speech is affected, which is how we use speech and the social aspects of speech, so the person may interrupt, not follow convention as far as greetings, etc go; may stray off topic, and may not understand the implications of tone of voice such as the intent of the speaker or the presence of things like irony or humor.  Additionally, the sound of the person's speech such as the rhythm may sound odd.  Right hemisphere dysfunction is also characterized by depression.  One form of right hemisphere dysfunction is called Non Verbal Learning Disorder (NVLD).

-Another type of APD is when the two hemispheres of the brain aren't able to work together well, called interhemispheric integration, which results in binaural deficits.  This can show up as difficulty when different inputs are given to each ear at the same time, and in identifying tones.  This type becomes more common as people age.

This is how the author responds to those who doubt that APD is real:
"Some children and adults exhibit extreme difficulties in primarily, if not solely, the auditory modality that affect their day-to-day learning and communication abilities.

For the majority of these individuals, hearing loss simply cannot account for their difficulties.  

These individuals exhibit specific patterns of findings on tests of central auditory function that precisely mirror those of known pathologies involving the central auditory nervous system and nothing else, which cannot be ignored or put down to mere coincidence."

 

 

Baroreflex Dysfunction

Baroreflex Failure- Vanderbilt University

Regulation of blood pressure with baroreceptors |NCLEX-RN|- YouTube Khan Academy 

Baroreflex Regulation of Blood Pressure- Alila Medical Medical

21.4 Baroreflex- YouTube UChicago Online.

Mast Cells and Hormones

Production, Clearance, and Measurement of Steroid Hormones

Progesterone

Progesterone inhibits mast cell secretion
"Mast cells express high affinity estrogen receptors and estradiol augments their secretion, while tamoxifen inhibits it. Here we report that progesterone (100 nM), but not the structurally related cholesterol, inhibits histamine secretion from purified rat peritoneal mast cells stimulated immunologically or by substance P (SP), an effect also documented by electron microscopy. These results suggest that mast cell secretion may be regulated by progesterone and may explain the reduced symptoms of certain inflammatory conditions during pregnancy."

Progesterone triggers selective mast cell secretion of 5-hydroxytryptamine
"When tested on purified rat peritoneal mast cells, progesterone alone stimulated release only of 5-hydroxytryptamine (serotonin) in a dose- and time-dependent manner. Serotonin release by progesterone was exceptional because it was not accompanied by histamine release or degranulation and was either augmented or unaffected by drugs which inhibit secretion induced by the classic mast cell secretagogue, compound 48/80. These findings indicate that mast cells are capable of selective serotonin secretion, previously shown only after pretreatment with certain tricyclic drugs, and may be involved in neuroendocrine syndromes."

Estrogen 

Carbachol-induced bladder mast cell activation: augmentation by estradiol and implications for interstitial cystitis
"Carbachol triggered rat bladder mast cell serotonin release in a dose-dependent manner, an effect increased by tissue pretreatment with estradiol"

Estradiol activates mast cells via a non-genomic estrogen receptor-alpha and calcium influx.
"Binding of physiological concentrations of estradiol to a membrane estrogen receptor-alpha initiates a rapid onset and progressive influx of extracellular Ca(2+), which supports the synthesis and release of allergic mediators. Estradiol also enhances IgE-dependent mast cell activation, resulting in a shift of the allergen dose response."

Environmental estrogens induce mast cell degranulation and enhance IgE-mediated release of allergic mediators
"All of the environmental estrogens tested caused rapid, dose-related release of beta-hexosaminidase from mast cells and enhanced IgE-mediated release. The combination of physiologic concentrations of 17beta-estradiol and several concentrations of environmental estrogens had additive effects on mast cell degranulation. Comparison of bone marrow mast cells from ER-alpha-sufficient and ER-alpha-deficient mice indicated that much of the effect of environmental estrogens was mediated by ER-alpha."

Testosterone

Testosterone exerts selective anti-inflammatory effects on human skin mast cells in a cell subset dependent manner
"While fundamental MC properties (FcεRI, c-Kit, tryptase; histamine release upon FcεRI cross-linking) were unaffected or slightly reduced (chymase) by testosterone, the hormone had a more profound impact on the production of cytokines, with IL-6 being a target (reduction by 53%). Interestingly, this effect was limited to breast skin MCs (15 of 16 donors displayed this phenomenon), but was not reproduced by foreskin MCs. Collectively, effector functions of human skin MCs are modulated by androgens in a gene-selective and MC subset-specific fashion. Possibly, MCs from women are more susceptible to testosterone. We also demonstrate that MC IL-6 production is highly variable among individuals."

 

 

Lymphatic Health

Dry brushing for lymphatic drainage and support

Med Establishment STUNNED By Brain Discovery THAT CHANGES EVERYTHING
Shalin Bhatt, a med student, discovered that there is a lymphatic connection with the brain (it was previously believed that there was no connection between the CNS and the lymphatic system).  This discovery shows us that NOT everything has been discovered by western medicine.  It also has implications for the function of the immune system and the gut-brain connection and much more.  

He calls his discovery the "Cerebrolymph Hypothesis" which he describes as an "anatomical framework for where CSF is produced".  CSF (cerebrospinal fluid) is produced in the deep brain region called the Choroid Plexus in the Ventricular System then it travels through the Subarachnoid Space (recently dubbed the Glymphatic System), then through the Meningeal Lymphatic Vessels into the last step (which is what he discovered) which is the Nerve-Adjacent Lymphatic Vessels Exiting Foramina.  This is where the fluid then enters the Peripheral Lymphatic System, the connection was not previously known.  This is essentially the "cleaning system" of the brain.  

This has implications for Alzheimer's research which has thus far focused on the proteins that build up in the brain, the Amyloid Plaques and and Tau Protein, but has not included the aspect of the dynamics of the cleaning process that would normally keep these proteins from building up in the first place.  This may lead to treatments that focus on repairing or maintaining the flow of lymph in the neck to treat or avoid Alzheimer's.  Shalin remarks that a lot of medical research is studying and validating traditional therapies (in this case acupuncture).  He mentions research showing benefits of acupuncture for Long COVID patients as well as Lymphedema and the associated brain fog.  Eastern medicine often considers the importance of flow in the body- could this be a concrete example?

This same researcher also published a theory recently called Glymphovasomotor Field Theory (GVF) which takes the idea that when a fluid moves (or circulates) that has ions in it, it creates an electromagnetic current, and applies it to the brain- if the CSF has ions in it and it moves through a structured flow pattern, maybe it creates an electromagnetic field- and maybe those fields effect neurons (which operate via electrical impulses).  This may have implications for consciousness.  

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:

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.