Landau-Kleffner Syndrome and Autism

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of children with LKS also develops serious behavioral dysfunction, including hyperactivity, temper outbursts, or withdrawn behaviors but rarely the severe social impairments seen in autism spectrum disorders.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

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

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

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

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

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

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

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

 

 

 

Mitochondria and Mental Health

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

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

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

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

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

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

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

What options are available to support mitochondrial functioning?

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

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

What about other interventions to support mito health?

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

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

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

 

 

 

 

 

 

Basics of the Ketogenic DIet

The ketogenic diet is based on the idea of eating in such a way as to make fats the fuel that the body burns for energy rather than sugar.  During digestion fats are broken down into molecules that are called ketones and then burns the ketones as fuel.  Ketones burn more "cleanly" than sugar does, which is the fuel burned by most people who live in industrialized, developed nations.  This keeps blood sugar, and therefore insulin, levels low.  This diet is especially effective for healing neurological problems such as seizures.  It is NOT the same thing as diabetic ketoacidosis.  In the more mainstream medical community a keto diet is defined entirely by the ration of macronutrients in a person's diet, so can include a lot of poor quality processed foods that are not healthy to eat.  The term "healthy keto" refers to a ketogenic diet that is based not only on macronutrient ratios but also on eating foods that are nutrient dense, relatively unprocessed, organic when possible, and which include a wide variety of foods to provide a wide variety of nutrients.  

The guidelines for keto say that of the calories you consume, 20% should be from protein, 65-70% fat, and 5% carbs.  This is difficult for many people to follow because it means calculating how many calories are in different foods.  A way to simplify this is for about half of what is in your plate to be vegetables and salad, about one-quarter to be protein, and the last quarter to be fat.  This seems like not enough fat, but keep in mind that one gram of fat has more than double the calories of one gram of protein or carbohydrates. 

Good sources of information regarding the ketogenic diet:
Andrew Huberman
Dr Boz (Annette Bosworth, MD)

NOTES-

-Need to keep insulin low to burn fat.  Eating, especially eating carbs, triggers the release of insulin.
A common misconception is that eating a high amount of fat is what puts you into ketosis, but it's actually reducing the amount of sugar and starch that determines this.  Lean meat and other protein sources will also trigger the release of insulin, although less.
-Avoid eating grains, sugars, or other starches.  Sugar alcohols (such as xylitol) are allowed but are associated with other health issues including blood clotting, heart attack, and stroke.  Avoid fruit except for some berries (blackberries, strawberries, and raspberries). 
-Eat 7 cups of veggies everyday.  Can help to eat them before eating protein.  No potatoes, but carrots and beets are okay. 
-Eat proteins with fat rather than lean meats/proteins.  This allows you to absorb the fat soluble vitamins such as vitamin D, A, E and K better.
-Eat less often and only when you are actually hungry.  A good schedule is to begin eating around noon and stop eating in the evening, a few hours before bed. 
-Coffee in the morning is fine if you have it black or with butter or MCT oil (use a blender to do this).
-There is normally a spike in cortisol around 8 AM and this can cause you to feel hungry.  This feeling will pass within 30 minutes or so.
-The glycemic index tells you how specific foods influence blood sugar levels, and the insulin index which tells you how non-carb foods influence insulin levels.  The leaner the meat/protein the more insulin is released.  Fat has a neutral effect on insulin levels.
-Suggestions of what to eat include 2 to 4 eggs per day, avocado, bacon, salmon, sardines and other fish, seafood, chicken with the skin on or chicken wings, cheese from grass-fed animals if dairy is tolerated, heavy whipping cream, nut and seed butters, olives, green salads, raw and steamed vegetables, olive oil and balsamic vinegar for salad dressing, handful of nuts and seeds, water with ACV and fresh lemon, coffee or tea (can be "bulletproof" with fat such as butter or MCT oil blended in), blueberries, raspberries, and strawberries.
-Taking exogenous ketones is especially good for people with a lot of insulin resistance. 
-It's okay to take vitamin supplements. 
-If you crave bread you may need more B vitamins.
-If you have gut dysbiosis or SIBO you might feel bloated and unwell after eating vegetables because the fiber is feeding gut bacteria that are in the wrong place.
-Electrolytes in water can help the transition to keto go smoothly. 
-Use sea salt and you will probably need more salt, at least at first.
-Get exercise while fasting, don't eat before or after exercise because insulin turns off fat burning.
- Coconut milk is keto-friendly, coconut water less so.

Mark's Daily Apple on why fat is the better fuel:

Get rid of Insulin Resistance Once And For All (from Dr Boz)
There are three factors about food that influence how much insulin we make.  They are the type of food, the size of the food, and the time the food is eaten.  All food stimulates insulin release, but carbs do it the most.  Protein (especially if lean) raises insulin somewhat, and fat does only a little.  It takes about 4 to 6 hours for insulin levels to return to normal after eating (in healthy people).  As for the effect of food size, if the food is ground up or pulverized it will cause more insulin to be released, so protein powders, grain flours, sugar, and powdered fats raise insulin levels higher than the same food in its more natural form would.  Circadian rhythms tell our bodies to release some glucose every morning at round 6AM to get us going.  This doctor suggests only eating when the sun is up, never after dark, for her insulin resistant patients.  She says that eating food at night (late at night?) keeps blood sugar levels and insulin levels elevated all night.  She suggests compacting your eating time to breakfast only and no other eating.  She says to eat only whole foods, eat mostly fat with a small amount of protein, and lots of vegetables.   

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