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:

Medical and Physiological Underlying Causes of Mental Illness

See also- Autoimmune Encephalitis (including PANDAS/PANS)

See also- Mast Cells, MCAS, and Psychiatric Symptoms 

BBC Ideas: The misdiagnosis that sent me to psychiatric hospital
Hannah had autoimmune encephalitis but was misdiagnosed as mentally ill. 

Never fear, the gut bacteria are here: Estrogen and gut microbiome-brain axis interactions in fear extinction

The Misdiagnosis Machine: How Thyroid Problems Mimic the Symptoms of Mental Illness

Mitochondria - The Key To Disease and Mental Health with Dr. Martin Picard 

Are Mental Illnesses Really Metabolic Disorders? | with Dr. Chris Palmer 

Common antibiotic may reduce schizophrenia risk, study shows 

"Lyme Rage" Lyme rage: the explosive symptom that can destroy relationships 

Hypokalemia can cause delirium, depression, delusions, hallucinations, psychosis.  Physical signs include cramps, nausea, heart arrhythmia, fatigue, paralysis, tachycardia

Vitamin D deficiency Helps depression and can reduce suicide by 45% Veterans see Study.

The Lactic Acid Response to Alkalosis in Panic Disorder : An Integrative Review
"Panic patients consistently show exaggerated lactic acid response to alkalosis, whether produced by hyperventilation or by sodium lactate infusion. Understanding why this occurs may provide important clues to the pathogenesis of panic disorder. Although brain hypoxia from excessive hypocapnia-induced cerebral vasoconstriction is often cited as the mechanism of elevated brain lactic acid in panic disorder, studies of brain metabolism show that hypocapnia rarely leads to brain hypoxia. Increased lactic acid production is a normal response to intracellular alkalosis and to intracellular cyclic AMP. Thus, other possible mechanisms of the exaggerated lactic acid response in panic disorder include a disturbance of mechanisms regulating intracellular pH and factors increasing intracellular cyclic AMP. Both mechanisms are consistent with the suffocation false alarm theory of panic disorder. This review suggests a theoretical framework for future magnetic resonance spectroscopy studies that can test some of the predictions of these competing models."

"Cerebellar Cognitive Affective Syndrome: Anatomy & Implications" - Jeremy D. Schmahmann, MD
A patient with dementia and schizophrenia returns to previous functioning after surgery to correct a chiari and syrinx.  Symptoms included school failure, manic, obsessive, compulsive, ruminative, treated for ADHD with poor results, anxiety, racing thoughts, hostile/aggressive, poor processing of conversations and loss of social skills, profanities, meanness, headaches, gait abnormalities, reclusive, depression.  After treatment, psychiatric issues gone, IQ still 148 but grades not fully back.

Another case- developmental delay, expressive language more affected than receptive, sensory-motor, executive function impairments, ASD diagnosis.  “seizure-like episodes” confusion, involuntary movements, uncharacteristic behaviors in “episodes”.  Worsening- autism, OCD, communication shut down, worse anxiety, tics; intrusive thoughts, ritualistic behaviors, insomnia, trance-like states in which he doesn’t seem to know his location or recognize his family.  Car rides would create “sensory episodes”.  Self-injury, laughing/coughing episodes, inappropriate laughter.  Decompression of brain stem ended seizure/tremor like episodes and pain, present and enjoying family, still reserved.  “It is apparent that the decompression of the brain stem/cerebellum/medulla and restoration of the CFS flow has eliminated the seizure-like tremoring, and other acute neurologic havoc that escalated to a dangerous neuro-psychiatric state when left unaddressed or otherwise mistreated for 11 months.”
“Phenomenon of autistic-like behaviors that resolve after decompression surgery” 
Cerebellar syndrome started as gait impairment, speech trouble, difficulty coordinating arms, oculomotor abnormalities.  Most of the cerebellum in humans is not related to motor control.  CURRENT- executive function (planning, set shifting, verbal fluency, abstract reasoning, working memory), spatial cognition (visual spatial organization and memory), language deficits (agrammatism, aprosodia, anomia), personality change (blunting of affect, disinhibited and inappropriate behavior).  Trouble multitasking.  In kids, memory problems can look like dissociation, fracturing.  Cerebellar Mutism Syndrome-maximally severe CCAS- profound buccofacial apraxia and apraxia of speech, emotional dysmetria, may include ataxia and cranial nerve palsies.  Cerebellar agenesis- surprisingly good motor abilities, child-like speech, reduced intellectual and executive functioning.  No ataxias in which cognition is entirely spared.  
“cerebellum optimizes performance by modulating behavior around a homeostatic baseline automatically, implicitly, and according to context.  

MCAS and Psychiatric Symptoms

Mast Cells, MCAS, and Psychiatric Symptoms

Brain mast cells link the immune system to anxiety-like behavior
"Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior."

"Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links."

Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome
"MCAS subjects have significantly elevated odds ratios for many neuropsychiatric disorders and may see improvement of symptoms using MCAS-targeted therapies, suggesting that mast cell dysregulation affects the brain and peripheral nervous systems and contributes to neuropsychiatric symptoms."

Mast Cell Activation & Inflammation in Brain Disorders: How to Calm Things Down
"Though our culture is only starting to consider psychiatric conditions as inflammation of the brain, if you or someone you know has panic attacks, depression, mood swings, ADHD, brain fog, chronic fatigue, PTSD, autism, cognitive issues or even dementia, then you know the destruction neuroinflammation plays in people’s lives.

Tweaking neurotransmitter functioning, the primary role of modern conventional psychiatry, isn’t the same as treating inflammation in the brain.  While psychotropic medications may help lessen symptoms (and can be life saving), they don’t address root causes including inflammation. In those with high immune reactivity, they may even trigger an inflammatory response themselves."

Brain inflammation has a lot to do with the interactions between mast cells, microglial cells, and CRH (corticotropin releasing hormone), which both triggers these cells and is released by them under stress.  This can be either physiological or emotional stress.  Examples of things can alter our stress response and contribute to chronic inflammation in the brain include toxic metals, chronic infections such as viruses and yeast overgrowth, mold exposure, trauma, and early disruption of healthy attachment.  Stress calls for cortisol, so CRH is released to signal the adrenal glands to release mroe cortisol, which also activates mast cells and microglial cells, leading to chronic brain inflammation, which in turn can damage the brain and lead to neurodegeneration.  

Research is also showing the role of mast cells in traumatic brain injury, multiple sclerosis, Parkinson’s disease, dementia, Alzheimer’s disease, stress conditions, sleep disorders, migraine, pain, ADHD and autism.  When mast cells are stimulated they disrupt and release mediators that increase the permeability of what we call the Blood Brain Barrier (BBB) and Gut Blood Barrier (GBB).  If microglia are overstimulated, "they will release their own inflammatory mediators causing local inflammation and disrupted connections between neurons.  If this goes on too long, nearby neurons will die which leads to neurodegeneration which can equate to the beginning of dementia."

Mast Cells, Stress, Fear and Autism Spectrum Disorder
“Prenatal stress has been associated with higher risk of developing ASD in the offspring. Moreover, children with ASD cannot handle anxiety and respond disproportionately even to otherwise benign triggers. Stress and environmental stimuli trigger the unique immune cells, mast cells, which could then trigger microglia leading to abnormal synaptic pruning and dysfunctional neuronal connectivity. This process could alter the “fear threshold” in the amygdala and lead to an exaggerated “fight-or-flight” reaction. The combination of corticotropin-releasing hormone (CRH), secreted under stress, together with environmental stimuli could be major contributors to the pathogenesis of ASD. Recognizing these associations and preventing stimulation of mast cells and/or microglia could greatly benefit ASD patients.”

Mast Cells and Stress- a psychoneuroimmunological perspective

Mast cells regulate blood-brain-barrier permeability from acute stress 

Mast cells can cause permeability of the blood-brain-barrier and contribute to neurological disorders  

Microglia and mast cells: two tracks on the road to neuroinflammation.

Neural circuitry engaged by prostaglandins during the sickness syndrome

Mast cell activation disease: an underappreciated cause of neurologic and psychiatric symptoms and diseases

 
Mast cell disease causes neurological and psychiatric symptoms and diseases

 

Mast Cells Affect Brain Physiology and Behavior

 
Mast Cell Disease can manifest as Mixed Organic Brain Syndrome (psychiatric symptoms)

 
Neuropsychiatric Manifestations of Mast Cell Activation Syndrome and Response to Mast-Cell-Directed Treatment: A Case Series

 
The Role of Mast Cells in Alzheimer's Disease.

 
Mast cells and migraine pathways