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.  

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. 

 

 

 

 

 

 

Mast Cell Activation Syndrome and the Vagus Nerve

These are my notes from the article "Mast cell activation syndrome and the vagus nerve"
written by Ross Hauser, MD of Caring Medical on February 4, 2023 

Many patients diagnosed with MCAS (Mast Cell Activation Syndrome) also have neck pain that is diagnosed as (or can be described as) upper cervical instability or cervical spine instability.  It is generally assumed that this pain is part of the existing illness, but in this article Dr Hauser explains that the causality could be going the other way.  Many of these patients are also diagnosed with  Chronic Fatigue Syndrome, Myalgic Encephalomyelitis (ME/CFS), POTS, or some other form of Dysautonomia.  When these patients see specialists to see if the neck pain and problems could be causing some of their symptoms, some are then diagnosed with "degenerative disc disease in their cervical spine and a loss of the cervical curve contributing to kyphosis".Dr Hauser explains that:

"Which brings us to an important question, which came first? Autonomic nervous dysfunction or immune-mediated allergy?  At a minimum, we know they are interconnected. A lot of antigen-antibody immune complexes and a host of histamine releases are going to excite the autonomic nervous system throughout and likewise, autonomic nervous system dysfunction makes antigen-antibody reactions more likely. The patient has the symptoms, is it the neck causing them? Is it the allergies?"

He explains that the way cervical instability could lead to symptoms of MCAS, etc, is because it may be causing the vagus nerve to be pinched or compressed in the neck or: "damaged cervical ligaments’ inability to hold the “wandering” vertebrae in place."  The vagus nerve is how signals from the brain reach the viscera (the organs in your torso) in order to control them, so anything that impedes its function can have major consequences:

"When the vagal nerve sensory afferents are dysfunctional, the important body sensors for homeostasis are switched off. Cervicovagopthy or vagus nerve disorder brought on by cervical spine instability, has wide-ranging negative effects on mucosal barriers in the intestines and lungs, producing a large number of inflammatory mediators, including histamine."

Dr Hauser explains that many patients who fit this profile- having MCAS along with many of the following additional diagnoses- EDS (Ehlers-Danlos Syndrome, POTS (Postural Orthostatic Tachycardia Syndrome), Gastroparesis, Fibromyalgia, sleep disturbances, low blood pressure, serious gastrointestinal pain and dysfunction, "When someone has a myriad of symptoms like this, it is of course difficult to believe they all start spontaneously without a common thread linking them together. In a person like this, when all is a mystery, we follow the neurology, we look for short-circuiting messages between brain and body being caused by compression of the arteries, veins, and the nerves that travel through the cervical spine."

Dr Hauser notes that many of the different disorders and symptoms experienced by these patients Do have established connections and that these connections are further evidence of vagus nerve involvement.  A key example of this is the interconnection between the immune system and the gut, mediated by the vagus nerve, in which modulating signals are sent both ways.  Also, regulating signals and neurotransmitters in this system are part of the mechanism that the body uses to turn inflammation on and off.  To explain this he quotes a may 2021 study in the journal Frontiers in Pharmacology:

“Inflammatory bowel disease, irritable bowel syndrome, and severe central nervous system injury (of which the vagus nerve plays a dominant role) can lead to intestinal mucosal barrier damage, which can cause endotoxin/enterobacteria translocation (movement, or better thought of as escaping to other parts of the body) to induce infection and is closely related to the progression of metabolic diseases, cardiovascular and cerebrovascular diseases, tumors and other diseases.”

"The researchers add that repairing the intestinal barrier represents a potential therapeutic target for many diseases. Repair means addressing the dysfunction of enteral afferent nerves, efferent nerves, and the intrinsic enteric nervous system that play key roles in regulating intestinal physiological homeostasis and coping with acute stress. Furthermore, innervation actively regulates immunity and induces inherent and adaptive immune responses through complex processes, such as secreting neurotransmitters or hormones and regulating their corresponding receptors."

"Histamine is synthesized by mast cells, basophils, platelets, histaminergic neurons, and enterochromaffin cells, where it is stored intracellularly and released upon stimulation. It can be found basically everywhere in the body, including the spinal cord and brain. Histamine causes smooth muscle cell contraction, vasodilation, increased vascular permeability and mucus secretion, tachycardia, alterations of blood pressure, and arrhythmias, while it stimulates gastric secretion and nociceptive nerve fibers. Histamine increases secretions such as hydrochloric acid in the stomach and is vital to protecting the lungs and gastrointestinal tract from infections. When histamine levels are high, increased secretions in the lungs, therefore, cause coughing, phlegm production, sneezing, and diarrhea occur in the digestive tract in an attempt by the body to rid itself of an infectious agent or toxin."

When the transmission of nerve impulses along the vagus nerve from the brain are interrupted or stopped, this can limit the body's ability to regulate and maintain homeostasis (balance of systems), which can keep the body from appropriately limiting the inflammatory response.  It also results in higher histamine content of mast cells, mast cells being more responsive to nerve signals to react, which ultimately means a higher level of histamine in the organs systems.  

"The GI tract harbors the largest population of mast cells in the body and is thus the main reservoir of the body’s histamine. The mast cells’ job is to maintain intestinal permeability and make sure that no microorganisms or antigens enter the body. (A dysfunction of this system can lead to Leaky Gut Syndrome and inflammation of the intestines.) The neurological control over mast cells and their various digestive functions is via the vagal influences on the enteric nervous system.  Elevated histamine levels in the body occur when there is an increase in intestinal permeability (regardless of the cause), including that from synthetic foods (industrial food additives, chemicals in food, genetically modified foods), Ehlers-Danlos syndrome (EDS), and cervical spine instability induced cervicovagopathy."

The effects of histamine on gut function, and how this impacts other disease processes especially autoimmune, has been well-studied.  Some common industrial food additives are known to trigger mast cells to make the gut more permeable (increase the amount of space between cells that line the gut and regulate what gets into the bloodstream and what doesn't), allowing larger proteins than usual into the bloodstream.  Once there, these proteins can trigger allergic and other inflammatory responses and are especially associated with autoimmune disease.  

"Histamine intolerance results from excessive histamine and a decreased ability to absorb or neutralize it.  Elevated levels of histamine give symptoms that mimic allergic reactions, and these include diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritis, flushing, and skin lesions. A true allergy is tied to IgE-mediated histamine release, which is to be differentiated from histamine intolerance. The latter is associated with some forms of urticaria, eczema, asthma, food sensitivity, migraines, and chronic GI and neurological ailments, including inflammatory and irritable bowel syndromes."

"The reservoir of histamine in the body originates in the gut and comes from the breakdown of food that is ingested or the microbiota-generated histamine. Histamine intolerance is akin to lactose intolerance in that the body is missing a key enzyme to digest a food substance. In histamine intolerance, it is DAO in the digestive tract, a deficiency of which leads to elevated histamine levels in the body. DAO is synthesized by the intestinal villi (enterocytes) and is constantly released from the intestinal mucosa into the gut, as well as the blood circulation, during eating and digestion."

Mast cell dysfunction is also being increasingly recognized as a major part of many neurological and psychiatric disorders, especially neurodegenerative disease.  "What is being suggested is that the Mast cells are causing runaway neurological inflammation by excerpting a disruptive influence (bad messages) on the central nervous system and brain and this is leading to neurodegenerative disorders such as Parkinson’s disease and Alzheimer’s disease for example." 

"vagal activity, partially driven by gastric mast cells, induces long-lasting changes in corticotrophin-releasing factor signaling in the amygdala that may be responsible for enhanced pain and enhanced anxiety- and depression-like behaviors."

"What they found was vagus nerve stimulation resulted in a significant reduction of the different inflammatory parameters assessed. They said their results underscore the anti-inflammatory properties of the vagus nerve and the potential of neuro-immune interactions in the intestine.  In other words, if the vagus nerve is working correctly, anti-inflammatory and mast cell activation could be suppressed."

Further Information from Dr Hauser:
Can Chronic fatigue syndrome and Myalgic encephalomyelitis be caused by cervical stenosis and cervical spine instability? 

Postural Orthostatic Tachycardia Syndrome (POTS), the Vagus Nerve and Cervical Spine instability

Treatments for Neck Pain and Cervical Instability: A review of upper cervical instability and symptom treatment with Ross Hauser, MD

Cervical Curve Correction – Caring Cervical Realignment Therapy

Research Articles Cited in this Article (not all):
How to evaluate the patient with a suspected mast cell disorder and how/when to manage symptoms

Diagnosis of mast cell activation syndrome: a global "consensus-2"

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM-Adjusted Proposal of the ECNM-AIM Consortium

Evaluation and Classification of Mast Cell Disorders: A Difficult to Manage Pathology in Clinical Practice

Intestinal Mucosal Barrier Is Regulated by Intestinal Tract Neuro-Immune Interplay

The Gut's Little Brain in Control of Intestinal Immunity

Vagal gut-brain signaling mediates amygdaloid plasticity, affect, and pain in a functional dyspepsia model

Vagus nerve stimulation dampens intestinal inflammation in a murine model of experimental food allergy

Keto Recipes and Food Ideas

Basic Foods- avocado, bacon, beef salami, sauerkraut, pickles, artichoke hearts

Basic Eggs- scrambled, fried, soft boiled, poached, hard boiled, baked/coddled.

Egg Dishes
Bombay Frittata (may need to modify cheese/dairy part)
Italian Baked Eggs
Thai Marbled Eggs (omit rice and sugar)
Tiger Eggs
Scotch Eggs

Frittata Variations
Asparagus, artichoke hearts, arugula, chard, bell peppers, broccoli, onions, leeks
Chives, cilantro, dill, parsley, basil, mint, garlic
Bacon, sausage, smoked salmon, salami
Cheese, capers

Snacks and "Fat Bombs"
Crispy Prosciutto Chips
Chicken Cracklins
Chinese tea eggs
Deviled Eggs
Egg Salad
Jerky (beef, beef heart, salmon)
Bacon Beef Liver Pate
Smoked salmon, other fish, oysters, clams

Green Salad Variations
Lettuce, arugula, watercress, other greens
Fresh herbs including basil, dill, parsley, cilantro, mint
Carrots, radishes, bell peppers, beets, red onions
Olive oil, avocado oil, coconut oil, pumpkin seed oil, grapeseed oil, sesame oil, bacon fat
Apple cider vinegar, balsamic vinegar, red wine vinegar, pickle brine
Lemon juice, lime juice, tart cherry juice, pomegranate juice
Pumpkin seeds, sesame seeds, sprouts, tomato, avocado, celery, green onions
Fresh ginger, fresh turmeric, garlic

Salads and Vegetable Dishes
Salade Lyonnaise (salad with poached egg on top)
Chef's Salad
Chinese Watercress With Garlic Stir Fry
Coleslaw ( mayo style, Indian style, Asian style)
Artichokes with Garlic Aoli
Caprese Salad (sub avocado for fresh mozzarella)

Sauces and Condiments
Crispy Garlic
Mayonnaise
Balsamic Vinaigrette
Pesto (nut free)
Guacamole
Fresh Salsa
Salsa Verde
Sesame Sauce

Meat and Main Dishes
Cantonese Ground Beef (skip the cornstarch and rice, modify sauces as needed)
Grilled or Oven-Roasted Santa Maria Tri-Tip (beef)
Fish Larb (omit rice and sugar)
Herby Pork Larb
Kai Sega Wat (Spicy Ethiopian Beef Stew)
Shredded Beef (taco style, korean barbecue style)
Sesame Chicken
Greek Lamb Shanks
Lamb Chops with Rosemary
Grilled Gochujang Pork With Fresh Sesame Kimchi
Vietnamese Slow Cooker Pork
Pulled Pork
Thai Pepper Pork
Pork Chops (grilled, dry rub, cast iron)
Pork Breakfast Sausage Patties
Kielbasa
Ham hocks with collards
Steamed Clams or Mussels
Seared Scallops
Baked Salmon (with dill, lemon, curry sauce)

Common Keto pizza crust recipe (uses dairy)
2 cups grated cauliflower
2 cups shredded mozzarella cheese 
2 eggs 
optional herbs- oregano, basil, thyme, garlic/garlic powder, nutritional yeast

Blend in food processor, spread on silicone baking mat.
Bake at 450 degrees for 15 minutes, then top with sauce, cheese, and toppings, and bake until cheese is melted.

Serotonin Syndrome (aka Serotonin Toxicity or Serotonin Storm)

What is Serotonin Syndrome?
Serotonin Syndrome is a condition that occurs when levels of serotonin, a neurotransmitter, rise too high and specific serotonin receptors are overstimulated.  Symptoms can be mild and often begin with headache, shaking and tremors, racing heart, nausea, feeling too hot, and mild anxiety and confusion.  Progressive symptoms can include diarrhea, vomiting, and other digestive system symptoms; hyperthermia, clonus, hyperreflexia, and an increase in anxiety, OCD, and panic.  In some cases it can progress to life-threatening symptoms including seizures, cardiac symptoms, heart attack, severe hyperthermia, coma, and death.  In mild cases treatment is usually limited to removal of the causative medication(s).  In more serious cases the serotonin antagonist medications cyproheptadine or chlorpromazine can be used to rapidly reduce the level of serotonin in the body.  Moderate to severe cases are a medical emergency and require emergency medical treatment.  This syndrome is rarely recognized (or even known about) by most doctors and other medical personal including EMTs/paramedics and ER doctors and nurses (even specialists).  Those who are aware of it often have an oversimplified understanding of it's potential causes and presentations and are likely unaware of the few acute treatments available.

Serotonin may or may not be one of the mediators released from mast cells during a mast cell reaction, but mast cells do release PAF (platelet activating factor) that then stimulates platelets, which can release serotonin. This is something that mast cell patients should be aware of, as the potential for serotonin toxicity seems to be a possible complication of the disorder and it is even less recognized than standard mast cell reactions.  Additionally, the majority of serotonin in the body is in the digestive tract (about 80-90%) and blood platelets (about 10%) so disorders involving those two systems seem to also be risk factors (I will elaborate on these interactions in another post).  Acute Serotonin Storm resulting from the combination of SSRIs and MAOIs does seem to the most widely recognized case and is (in my experience) the most effective way to get a doctor or other medical provider to realize what you're talking about (the only way that I have successfully gotten doctors to take my serotonin sensitivity seriously is to tell them that I have genetics that mimic the situation in which a person is taking both an SSRI and an MAOI).  Genetic mutations involving enzymes that play a role in regulating serotonin levels in the body also seem to be significant in at least some patients, including myself (more on that in another post as well).

Drugs that have been reported to cause or contribute to serotonin toxicity include- SSRIs, SNRIs, MAOIs, tricyclic antidepressants, mirtazapine, venlafaxine, Zofran, opioids (opioids with serotonergic effects include the phenylpiperidine series opioids fentanyl, methadone, meperidine and tramadol and the morphine analogues oxycodone and codeine), Methylene Blue, cannabis/marijuana, lithium, sodium valproate, 

More information about serotonin syndrome...  (emphasis added)

Overview of serotonin syndrome.

"SS commonly occurs after the use of serotonergic agents alone or in combination with monoamine oxidase inhibitors. SS classically consists of a triad of signs and symptoms broadly characterized as alteration of mental status, abnormalities of neuromuscular tone, and autonomic hyperactivity.  However, all 3 triads of SS may not occur simultaneously. Clinical manifestations are diverse and nonspecific, which may lead to misdiagnosis. SS can range in severity from mild to life-threatening. Most cases of SS are mild and resolve with prompt recognition and supportive care. Management of SS involves withdrawal of the offending agent(s), aggressive supportive care to treat hyperthermia and autonomic dysfunction, and occasionally the administration of serotonin antagonists--cyproheptadine or chlorpromazine. Patients with moderate and severe cases of SS require inpatient hospitalization."

Serotonin syndrome: a complex but easily avoidable condition.

"Serotonin syndrome is a potentially life-threatening adverse drug reaction caused by excessive serotonergic agonism in central and peripheral nervous system serotonergic receptors. Symptoms are characterized by a triad of neuron-excitatory features, which include (a) neuromuscular hyperactivity -- tremor, clonus, myoclonus, hyperreflexia and, in advanced stages, pyramidal rigidity; (b) autonomic hyperactivity -- diaphoresis, fever, tachycardia and tachypnea; (c) altered mental status -- agitation, excitement and, in advanced stages, confusion. It arises when pharmacological agents increase serotonin neurotransmission at postsynaptic 5-hydroxytryptamine 1A and 5-hydroxytryptamine 2A receptors through increased serotonin synthesis, decreased serotonin metabolism, increased serotonin release, inhibition of serotonin reuptake or direct agonism of the serotonin receptors. The etiology is often the result of therapeutic drug use, intentional overdosing of serotonergic agents or complex interactions between drugs that directly or indirectly modulate the serotonin system. Due to the increasing availability of agents with serotonergic activity, physicians need to more aware of serotonin syndrome. "

The Serotonin Syndrome
Understanding the symptoms...

Tachypnea is a form of rapid breathing similar to hyperventilation, but differs in that it involves rapid shallow breathing whereas hyperventilation (at least in some medical references) refers to rapid deeper breathing and seems to be associated only with mental health disorders such as anxiety and panic, according to many medical sources.

What the Heck is Clonus?

In this video two physical therapists explain what clonus is and how to recognize it.  It is a form of involuntary tremor that is essentially part of a reflex that the body can't control due to an injury or disorder.  It can be limited to a few repetitions of a movement (such as the ankle moving up and down) or can become continuous.

The Many Presentations/Manifestations of Serotonin Syndrome

Mild serotonin syndrome: A report of 12 cases.

Headache as a presenting feature in patients with serotonin syndrome: a case series.

Serotonin syndrome in patients with headache disorders.

"Various serotonergic drugs are used in different headache disorders. Therefore, a possibility of developing SS exists in patients with headache. Herein, we are reporting two patients with headache disorders who developed SS.Case 1: a 49-year-old man had a 6-year history of episodic cluster headache (CH). However, he had never been diagnosed with CH before reporting to us. He had been receiving amitriptyline, tramadol/acetaminophen combination and flunarizine. Lithium was started for CH. He developed features consistent with SS. The patient responded to cyprohepatdine. Case 2: a 36-year-old chronic migraineur was on amitriptyline. Addition of sodium valproate led to the development of new features that fulfilled the criteria of SS. The patient responded to cyprohepatdine.  As SS may be fatal, there is a need to increase awareness about SS in physicians treating patients with headache."

Serotonin syndrome presenting as febrile encephalopathy with CSF pleocytosis: a report of three cases.

Serotonin syndrome presenting as surgical emergency: A report of two cases.

Psychiatric Emergencies for Clinicians: Emergency Department Management of Serotonin Syndrome

Generalized Itching and Lower-Extremity Spasticity in a Patient with Intrathecal Baclofen Pump

Serotonin syndrome presenting as hypotonic coma and apnea: potentially fatal complications of selective serotonin receptor inhibitor therapy.

Diagnosis and Management of Serotonin Syndrome
Prevention, Diagnosis, and Management of Serotonin Syndrome

Recognition and treatment of serotonin syndrome

The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity.

"Numerous clinical features were associated with serotonin toxicity, but only clonus (inducible, spontaneous or ocular), agitation, diaphoresis, tremor and hyperreflexia were needed for accurate prediction of serotonin toxicity as diagnosed by a clinical toxicologist. Although the learning dataset did not include patients with life-threatening serotonin toxicity, hypertonicity and maximum temperature 38 degrees C were universal in such patients; these features were therefore added. Using these seven clinical features, decision rules (the Hunter Serotonin Toxicity Criteria) were developed. These new criteria were simpler, more sensitive (84% vs. 75%) and more specific (97% vs. 96%) than Sternbach's criteria....  These redefined criteria for serotonin toxicity should be more sensitive to serotonin toxicity and less likely to yield false positives."

Serotonin toxicity: a practical approach to diagnosis and treatment.  

"Excess serotonin in the central nervous system leads to a condition commonly referred to as the serotonin syndrome, but better described as a spectrum of toxicity - serotonin toxicity. Serotonin toxicity is characterized by neuromuscular excitation (clonus, hyperreflexia, myoclonus, rigidity), autonomic stimulation (hyperthermia, tachycardia, diaphoresis, tremor, flushing) and changed mental state (anxiety, agitation, confusion). Serotonin toxicity can be: mild (serotonergic features that may or may not concern the patient); moderate (toxicity which causes significant distress and deserves treatment, but is not life-threatening); or severe (a medical emergency characterized by rapid onset of severe hyperthermia, muscle rigidity and multiple organ failure). Diagnosis of serotonin toxicity is often made on the basis of the presence of at least three of Sternbach's 10 clinical features. However, these features have very low specificity. The Hunter Serotonin Toxicity Criteria use a smaller, more specific set of clinical features for diagnosis, including clonus, which has been found to be more specific to serotonin toxicity. There are several drug mechanisms that cause excess serotonin, but severe serotonin toxicity only occurs with combinations of drugs acting at different sites, most commonly including a monoamine oxidase inhibitor and a serotonin reuptake inhibitor. Less severe toxicity occurs with other combinations, overdoses and even single-drug therapy in susceptible individuals. Treatment should focus on cessation of the serotonergic medication and supportive care. Some antiserotonergic agents have been used in clinical practice, but the preferred agent, dose and indications are not well defined."

Prevention, recognition, and management of serotonin syndrome.

Controversies in Serotonin Syndrome Diagnosis and Management: A Review.

 

This article is about the use of the amino acid lysine to treat herpes viruses, but it includes a section about the role of lysine in regulating serotonin and possible helping to treat and avoid serotonin toxicity.  From the article "Another potential use of lysine supplementation is in the treatment of depression and anxiety. It is thought that lysine deficiency results in a pathological increase in serotonin in the amygdala, which is responsible for emotional regulation and stress response. When serotonin increases unchecked, the amygdala becomes overstimulated, resulting in a low-level serotonin syndrome with anxiety, diarrhea, and other symptoms of excess serotonin."  The article then mentions a small study that found a small but significant improvement of mood from an increase of lysine-rich foods in the diet.  The article lists sources at the end.

 

Risks, Use and Management of Serotonergic Drugs

Serotonin syndrome resulting from drug interactions.

"We describe six patients diagnosed with serotonin syndrome after exposure to drugs with serotonergic activity. Drug interactions occurred as a result of a combination of tricyclic antidepressants, selective serotonin reuptake inhibitors, selective noradrenaline reuptake inhibitors or monoamine oxidase inhibitors. Management included supportive care and the use of non-specific serotonin antagonists (cyproheptadine, benzodiazepines and chlorpromazine). All patients made uneventful recoveries."

Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine.
"SS is a potentially fatal iatrogenic complication of serotonergic polypharmacy. Considered idiopathic in presentation, it typically appears after initiation or dose escalation of the offending agent to a regimen including other serotonergic agents. All drugs that directly or indirectly increase central serotonin neurotransmission at postsynaptic 5-HT(1A) and 5-HT(2A) receptors can produce SS. Individual vulnerability appears to play a role in the development of SS. It is likely that the activation of 5-HT(1A) receptors by mirtazapine, the combined serotonin reuptake inhibition by venlafaxine and tramadol, as well as possible serotonin release by tramadol, contributed to the development of SS in this case."

eComment: Serotonin syndrome: pharmacogenomics and treatment

Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity.

[Serotonin syndrome and pain medication : What is relevant for practice?].

"Opioids with serotonergic effects include the phenylpiperidine series opioids fentanyl, methadone, meperidine and tramadol and the morphine analogues oxycodone and codeine. In combination with certain serotonergic drugs, e.g. antidepressants, they can provoke serotonin syndrome. In patients with such combinations, special attention should be paid to clinical signs of serotonergic hyperactivity. Higher risk combinations (e.g. monoamine oxidase inhibitors with tramadol) must be avoided. Treatment with serotonergic agents must be stopped in moderate or severe serotonin syndrome. Patients with a severe serotonin syndrome require symptomatic intensive care and specifically a pharmacological antagonism with cyproheptadine or chlorpromazine."

Serotonin syndrome induced by fluvoxamine and oxycodone.
"A 70-year-old woman developed severe serotonergic features, including confusion, nausea, fever, clonus, hyperreflexia, hypertonia, shivering, and tachycardia, following the addition of oxycodone 40 mg twice daily to fluvoxamine 200 mg/day, easily fulfilling diagnostic criteria for serotonin syndrome. Discontinuation of the offending drugs resulted in resolution of her symptoms over 48 hours, and no other cause of the syndrome was identified."

Serotonin syndrome following cardiac surgery.

Serotonin syndrome caused by minimum doses of SSRIs in a patient with spinal cord injury.

Acute Treatment of Serotonin Toxicity (aka Serotonin Storm)

Treatment of the serotonin syndrome with cyproheptadine
"All patients were administered cyproheptadine (4–8 mg orally) for serotonergic signs. Three had complete resolution of signs within 2 h of administration. Another two had a residual tremor or hyperreflexia following the first dose, which resolved following a repeat dose. There were no adverse outcomes from cyproheptadine use. The role of specific serotonin receptor antagonists such as cyproheptadine in the treatment of the serotonin syndrome remains to be delineated. Its use should be considered an adjunct to supportive care. Currently, it is unknown whether cyproheptadine modifies patient outcome."

Chlorpromazine 

"Chlorpromazine is in the typical antipsychotic class. Its mechanism of action is not entirely clear but believed to be related to its ability as a dopamine antagonist. It also has anti-serotonergic and antihistaminergic properties."

The Neurological System- Relevant Symptoms, Conditions, and Disorders

The Following are symptoms and disorders of the neurological system that can occur with people who have the constellation of conditions and diagnoses that I and my family do.  The point of the list is not for us to diagnose ourselves, but rather to be aware of the possible connection between symptoms that we are having and our neurological system to help guide efforts to diagnose and treat the symptoms.  Some of these are considered controversial (in the sense that some doctors and other experts aren't convinced that they exist) so keep that in mind if discussing them with a doctor, but I included them because I have found knowledge of "controversial" things to be very helpful in getting appropriate care.

About the Brain and Neurological System:
There is still so much that is not known or well understood about the human brain and nervous system, how it works, and what can go wrong.  This leaves many people with significant neurological problems without much guidance or treatment.

NOVA "Secrets of the Mind"  (phantom limb pain, blindsight, etc)

Daniel Tammet TED talk "Different Ways of Knowing"

Anatomy Zone brain videos

What Does the Brain's Frontal Cortex Do? (Professor Robert Sapolsky Explains)

Specific Symptoms, Disorders, and Conditions:
Absence Seizure (aka Petite Mal Seizure | Epilepsy)

Anterior Cutaneous Nerve Entrapment Syndrome

This is when chronic abdominal pain is caused by a nerve that innervates the abdominal wall being pinched or compressed and causing a strong, localized pain.  Movement can make the pain worse, and lying on the back improves the pain.  ACNES occurs most often on young and middle aged women.  It is a benign situation that is normally treated with a trigger point injection of a pain med such as lidocaine along with a steroid.  If the pain persists the nerve that is causing the pain can be severed.

Alice in Wonderland Syndrome

 

Allodynia is pain that a person feels in response to a stimulus that wouldn't normally be painful, such as a very light touch.

Alzheimer’s Disease We Might Be Totally Wrong About Alzheimer’s

Anosognosia

Aphantasia

Auditory processing disorder "Auditory processing disorder (APD) is a hearing issue that makes it hard for you to understand what people are saying.  People with APD have difficulty understanding speech even though they don’t have hearing issues. Many APD symptoms are similar to hearing loss symptoms."

Benign Fasciculation Syndrome Causes and Treatment

Carbon Monoxide Brain Injury

Cerebral Folate Deficiency 

 

Cervicogenic Dizziness

Complex Regional Pain Syndrome (CRPS)

What happens when you have a concussion?

Dilated pupils

Dysautonomia ("Faces of Dysautonomia" awareness video)
Common symptoms of Dysautonomia from MedicalNewsToday include:
Difficulty standing, dizziness, vertigo, fainting; fast, slow or irregular heartbeat; chest pain, low blood pressure, problems with digestion, nausea, visual disturbances, weakness, fatigue, breathing problems, anxiety, mood swings, tremors, disordered sleep, frequent urination, difficulty regulating body temperature, problems with memory and concentration, poor appetite, and sensory sensitivities (often to sound and light).

What is Executive Function and Why Do We Need it? 

Exploding Head Syndrome

Guillain-Barre Syndrome is an auto-immune disorder in which the body's immune system attacks the myelin-producing cells of the Peripheral Nervous Syndrome (PNS).  Common symptoms are numbness, weakness, and even paralysis.  If the weakness/paralysis spreads to the muscled required for breathing, the disease can be fatal.  It is treated with IV/IG which is an infusion of blood containing antibodies from donors. 

Hallucination What hallucination reveals about our minds | Oliver Sacks

Hepatic Encephalopathy

Hyperlexia

Impostor Syndrome

 

Intracranial Hypertension 

 

Lhermitte's sign "(also known as Lhermitte's phenomenon or the barber chair phenomenon) is the term used that describes a transient sensation of an electric shock that extends down the spine and extremities upon flexion and/or movement of the neck.  The sign is suggestive of a lesion or compression of the lower brain stem or the upper cervical spinal cord. It is a paroxysmal sensation or neuropathic pain that can develop as a result of direct or indirect demyelinating lesions in the brain and/or spinal cord and is triggered by the flexion or movement of the neck. More specifically, the neck motion activates ascending spinothalamic tracts at the cervical level that has been sensitized by the underlying process that caused the cervical spine lesion."

Myoclonus

Nystagmus epilepticus

Narcolepsy

OCD- Pure O: Thinking the Unthinkable (Extreme OCD Documentary) 

PANDAS

Papilledema "Papilledema refers to the swelling of both optic discs in your eyes due to increased intracranial pressure (intracranial hypertension)."  If the cause is intracranial hypertension, both optic discs are usually affected.  If only one is affected it is most likely the result of something else.  Papilledema can be an emergency if it is caused by dangerously high intracranial pressure. 

Prosopagnosia

Peripheral neuropathy

 

Psychogenic Nonepileptic Seizures

 

Types of Seizures
Seizures are usually classified as generalized or focal. 

Selective Mutism My Child Won't Talk
BBC show about 3 girls with selective mutism, includes information about therapies that helped them.

What is Spasticity?

Synesthesia

PAIN DISORDERS
Complex Regional Pain Syndrome (CRPS)     
Central Sensitization Syndrome (and chronic pain)

Intractable Pain Disease 

Curing a mysterious nerve condition by inflicting unbearable pain | 60 Minutes Australia