Bridging Gaps in Research

Through a coordinated research effort involving patients, clinicians and researchers, the Brain Inflammation Collaborative strives to uncover connections between brain inflammation and mental and physical health and make advances in the diagnosis, treatment and prevention of neuroinflammatory illness.

The Unhide Project is an ongoing online clinical study that assembles patient-donated data to help clinicians and researchers accelerate breakthroughs surrounding brain inflammation and mental health.

Join the Movement

The relationship between brain inflammation and mental health is vastly understudied and misunderstood. The Brain Inflammation Collaborative is leading the charge to change that. Discover all the different ways you can support our mission to find long-overdue answers and solutions for patients.

Conditions of Interest

The beginning phase of illnesses we will be investigating include long COVID, OCD, anorexia nervosa, PANDAS, PANS, autoimmune encephalitis, Tourette’s, POTS, narcolepsy, and ME/CFS. Additional illnesses to be explored and added to our platform will include depression, PTSD, concussion, post mortem suicide, anxiety disorders, depression, auto-immune arthritis forms, Ehlers Danlos Syndrome (EDS), mast cell activation syndrome (MCAS), chronic sinusitis, anxiety disorders, small fiber neuropathy, psoriasis, and irritable bowel disease (IBD).

Illness Descriptions of Studied Diagnoses

Anorexia nervosa is an eating disorder where people experience an intense fear of gaining weight and typically hold a distorted perception of weight, which results in caloric restriction that then develops into an abnormally low body weight.

Avoidant restrictive eating disorder (ARFID) is a condition where people have a dramatic restriction in the types and amounts of food eaten. A person with ARFID does not eat enough calories to maintain basic body function. They can be concerned about the texture and appearance of food, or develop selective phobias about foods which can include fear of choking. The limited range of preferred foods can worsen over time. This is a more common issue for children but can pertain to any age group.

Both eating disorders are serious and include psychological issues around depression and anxiety that require supportive treatment. Anorexia nervosa is differentiated from ARFID based on severity of restriction and the potential life-threatening consequences.

People with anorexia use extreme efforts to control their weight and appearance, including calorie restriction, excessive exercising, vomiting after they eat, or misusing laxatives, diet aides, diuretics, or enemas.

Anorexia is characterized by both physical symptoms as well as emotional and behavioral problems. It can be hard to identify the signs of anorexia nervosa as people with anorexia often try to hide their thinness, eating habits, or physical symptoms.

Symptoms can include:

  • Extremely restricted eating
  • Extreme thinness (emaciation)
  • A relentless pursuit of thinness and unwillingness to maintain a normal or healthy weight
  • Intense fear of gaining weight
  • Distorted body image, self-esteem that is heavily influenced by perceptions of body weight and shape, or a denial of the seriousness of low body weight
  • Skin discoloration, brittleness of hair
  • Fatigue
  • Insomnia
  • Abnormal blood counts
  • Irregular heart rhythms
  • Low blood pressure
  • Absence of menstruation
  • Fatigue

Emotional and behavioral symptoms:

  • Intense fear of gaining weight, distorted body image
  • Preoccupation with food, including cooking elaborate meals for others but not eating them
  • Frequently skipping meals or refusing to eat
  • Denial of hunger or making excuses for not eating
  • Eating only a few “safe” foods that are usually low in fat and calories
  • Adopting stringent eating rituals like spitting out food after chewing
  • Not wanting to eat in public
  • Lying about how much has been eaten
  • Repeated weighing or measuring the body out of fear of weight gain
  • Checking the mirror frequently for perceived flaws
  • Complaining about being fat or having body parts that are fat
  • Covering up in layers of clothing
  • Lack of emotion
  • Social withdrawal
  • Irritability and depression
  • Reduced interest in sex

Diagnosis includes a physical exam, lab tests, and psychological evaluation. In treating anorexia, it’s important to understand that it isn’t really about food but rather the person’s way of coping with other problems. While nutritional counseling, psychotherapy, medication, and lifestyle changes are key to restoring a person to their healthy weight—the first goal in treatment—hospitalization, programs specializing in the treatment of eating disorders, and other medical care may be needed to treat anorexia.

Autoimmune encephalitis (AE) is a collection of serious but rare conditions occurring in around 14 out of 100,000 people. In AE, inflammation of the brain (or encephalitis) occurs when the body makes an antibody that mistakenly attacks the brain. What triggers an autoimmune reaction is not always well understood but can include exposure to certain tumors (e.g. ovarian teratoma), bacteria, and viruses (e.g. herpes simplex and SARS-CoV2).

During inflammation, patients can experience headache, neck pain, light and sound sensitivity, mental confusion, and seizures. AE typically progresses over the course of days to weeks and evolves from initial flu-like symptoms to functional neurologic or psychiatric disorders. There are many different types of AE (and more being discovered all the time), such as:

  • Anti-NMDA receptor encephalitis
  • Hashimoto’s encephalopathy
  • Acute disseminated encephalomyelitis (ADEM)
  • Limbic encephalitis
  • LGI1/CASPR2-antibody encephalitis
  • Anti-GABAA receptor encephalitis
  • Seronegative autoimmune encephalitis

Each type of AE has unique features, but common symptoms of AE may include:

  • Memory loss
  • Altered mental status (e.g., confusion, disorientation, irritability, cognitive impairment)
  • Psychiatric symptoms (e.g., anxiety, psychosis, hallucinations, behavioral changes)
  • Movement disorders
  • Difficulty with balance, speech, or vision
  • Sleep problems
  • Weakness or numbness
  • Loss of consciousness or coma

Autoimmune encephalitis is easily overlooked, as the signs and symptoms are similar to other more prevalent conditions, including mental health disorders or drug abuse. Discovery of autoantibodies (antibodies directed at the body’s own cells) in blood and cerebrospinal fluid has improved the ability to diagnose AE; however, brain imaging and other tests may be required to confirm an AE diagnosis.

The key to surviving autoimmune encephalitis is early detection and treatment. The approach used to treat AE usually involves a team of care specialists and depends on the underlying cause and symptoms. Treatments for AE include:

  • Immunomodulators (steroids, intravenous antibodies or IVIG, plasma exchange, immune suppression)
  • Antiviral medications and antibiotics (if a viral or bacterial infection is the root cause)
  • Anti-seizure medications
  • Surgery to remove a tumor,that%20mistakenly%20attack%20brain%20ce

Post-COVID-19 syndrome, also called long-haul COVID, describes a variety of ongoing, new, or returning symptoms experienced by people more than four weeks after getting COVID-19. Long-haul covid can last months or years and may lead to disability. The Household Pulse Survey found that 19% of U.S. adults who had COVID at least 3 months ago are still experiencing symptoms of long COVID, although newer variants may differ and data collection is ongoing.

Symptoms of post-COVID-19 syndrome include:

  • Fatigue
  • Fever
  • Symptoms that get worse after mental or physical effort
  • Respiratory symptoms (e.g., difficulty breathing, shortness of breath, cough)
  • Neurological symptoms (e.g., brain fog, headache, sleep problems, dizziness when standing upright, pin-and-needles feeling, loss of smell or taste, depression or anxiety)
  • Heart symptoms (e.g., chest pain, heart palpitations)
  • Digestive symptoms (e.g., diarrhea, stomach pain)
  • Blood clots and problems affecting the blood vessels
  • Joint or muscle pain
  • Rash
  • Change in menstrual cycle

A person is more likely to experience long-haul COVID if they:

  • have a severe case of COVID-19 (e.g., needed hospitalization or intensive care)
  • are unvaccinated against COVID-19
  • are female
  • smoke
  • are obese
  • have certain medical conditions prior to getting COVID-19

It can be difficult to tell if some symptoms are due to long-haul COVID or another condition. Many symptoms are similar to other chronic illnesses that develop following an infection. Increasingly, it appears that long-haul COVID may result from different mechanisms that could help categorize patients for treatment. For instance, people with breathlessness and fatigue from pneumonia damage to their lungs may be very different from those experiencing mostly brain fog and fatigue. A long-haul COVID diagnosis is based on medical history, a prior diagnosis of COVID-19, and clinical examination. Because symptoms vary greatly, a personalized health plan is used to manage post-COVID-19 syndrome.

Chronic fatigue syndrome, also called myalgic encephalomyelitis or ME/CFS, is a complex disease characterized by chronic fatigue that lasts at least six months. ME/CFS affects neurological, immunological, and metabolic functions. Symptoms do not improve with rest and worsen with even minimal physical or mental activity. Symptoms of ME/CFS include: 

  • Post-exertional fatigue
  • Sleep problems
  • Cognitive issues (problems with memory and thinking)
  • Dizziness that worsens when standing upright
  • Muscle or joint pain
  • Orthostatic intolerance
  • Sensory intolerance
  • Flu-like symptoms
  • Gastrointestinal symptoms

ME/CFS is a serious disease and most people who experience ME/CFS never regain their pre-disease level of functioning. According to the CDC, ME/CFS affects up to 2.5 million Americans and is more likely to occur in women than men.

While the underlying cause of ME/CFS is unknown, many people with ME/CFS report symptoms that persist following an acute infection. There is no single diagnostic test to confirm ME/CFS; rather, a diagnosis depends on ruling out other conditions with similar symptoms. No FDA-approved treatment for ME/CFS is currently available and treatment approaches focus on symptom relief.

Narcolepsy is a chronic neurological disorder affecting the sleep-wake cycles and the brain’s ability to control them. People with narcolepsy may unwillingly fall asleep—even in the middle of an activity like eating, talking, or driving. Left untreated, narcolepsy can interfere with cognitive function and development.

Within a normal sleep cycle, people enter REM sleep after 60-90 minutes, whereas in narcolepsy, people enter REM sleep after only 15 minutes. People with narcolepsy can also experience spells of muscle weakness while awake. 

Symptoms typically start in childhood, adolescence, or young adulthood, but are often misdiagnosed. While the causes of narcolepsy are not fully understood, low levels of hypocretin (a chemical that promotes wakefulness and regulates REM sleep) and other factors are thought to be involved (e.g., autoimmune attack on hypocretin-secreting parts of the brain, brain injuries, and genetics). Symptoms include:

  • Excessive daytime sleepiness (EDS) which comes on quickly and may be called a “sleep attack”
  • Cataplexy, the sudden loss of muscle tone while awake, leading to weakness or loss of voluntary muscle control (it is related to the paralysis of muscle activity that occurs during REM sleep)
  • Sleep paralysis, like cataplexy but occurring at the edges of sleep
  • Automatic behaviors, in which a person without conscious awareness automatically continues an action or activity interrupted by a brief sleep episode 
  • Hallucinations, the vivid and sometimes frightening images that accompany sleep paralysis
  • Fragmented sleep and insomnia

Diagnosing narcolepsy requires clinical evaluation to rule out other neurological conditions and two specialized tests: polysomnogram (PSG or sleep study) and multiple sleep latency test (MSLT). A doctor may ask the patient to keep a sleep journal to document sleep times and symptoms. There is no cure for narcolepsy, but symptoms can be managed with medication and lifestyle changes.

Obsessive compulsive disorder (OCD) is a condition where a person gets caught in a cycle of obsessions and compulsions. Obsessions are characterized as unwanted intrusive thoughts, images, or urges that trigger intense feelings such as fear, disgust, uncertainty, and doubt. Compulsions are the repetitive behaviors or thoughts used to neutralize, counteract, or get rid of obsessions.

OCD can affect people at any age and most commonly appears between ages 8 and 12 or between late teen years and early adulthood. In the US, it is estimated that 1 in 100 adults and at least 1 in 200 adolescents are currently living with OCD. 

To make an OCD diagnosis, the cycle of obsessions and compulsions must be so extreme and frequent that they take up more than an hour a day, cause intense distress, or get in the way of valued activities like going to school or work or spending time with friends. Common obsessions in OCD include:

  • Contamination obsessions
  • Sexual obsessions
  • Violent obsessions
  • Religious/Moral obsessions
  • Responsibility obsessions
  • Perfectionism-related obsessions
  • Identity obsessions
  • Relationship-related obsessions
  • Existential-themed obsessions
  • Real event/false memory obsessions

Common compulsions in OCD include:

  • Avoidance of triggers
  • Excessive washing and cleaning
  • Checking for mistakes or behaviors that could cause harm
  • Checking body parts or conditions
  • Repeating routine activities and body movements
  • Repeating activities in “multiples” (usually to satisfy a “safe” number)
  • Mental compulsions (eg, reviewing events, praying, counting)
  • Arranging or ordering things until they “feel right”
  • Telling, asking, or confessing to get reassurance

OCD is typically treated with a combination of cognitive behavioral therapy (CBT) and medication. More specifically, a type of CBT called exposure and response prevention (ERP) can help modify behaviors and thoughts associated with OCD, while a class of drugs called serotonin reuptake inhibitors (SRIs)—a widely used type of antidepressant—are thought to be uniquely effective to treat OCD.,Clomipramine%20(Anafranil)

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, or PANDAS, is a condition that affects children, and symptoms seemingly appear “overnight” following a group A streptococcal infection. Pediatric acute-onset neuropsychiatric syndrome (PANS) is a related disorder where the infectious trigger may be other types of infection or not identified. PANDAS/PANS often presents as obsessions or compulsions or restricted eating, and includes at least two other symptoms, including:

  • ADHD symptoms (e.g., hyperactivity, inattention, or fidgeting)
  • Separation anxiety
  • Mood changes (e.g., irritability, sadness, depression, behavioral regression)
  • Trouble sleeping
  • Nighttime bed-wetting
  • Frequent daytime urination
  • Change in motor skills (e.g., handwriting)
  • Decline in cognitive and executive function
  • Motor, sensory, or vocal abnormalities 
  • Joint pain

Initial treatment of PANDAS/PANS should importantly target any underlying infection using antibiotics, antiviral, or related antigen therapeutic. Further symptoms may be managed using a combination of medication, behavioral therapy, and cognitive behavioral therapy. In severe PANDAS, immunotherapy may be considered—research suggests plasma exchange or immunoglobulin (IVIG) can often improve neuropsychiatric symptoms associated with PANDAS.

The diagnosis and treatment of PANDAS/PANS is often difficult, as this is a relatively newly investigated disease. However, with the outbreak of the COVID-19 pandemic and widespread investigation of psychological reactions to coronavirus infection, there is an increase in research into why pathogens can affect the brain of some people but not others. Hopefully in the near future this will aid in making PANS or PANDAS easier to diagnose.

Tourette syndrome is a neurological disorder characterized by unwanted and uncontrolled movements or vocal sounds called tics. Motor or vocal tics are usually rapid and repeated and vary in type, frequency, and severity. Tourette syndrome is more prevalent in boys than girls, and tics usually appear between ages 5 and 10 years and may come and go over time. 

Motor tics typically start by affecting the head and neck and progress to affect muscles of the torso, arms, and legs. Development of vocal tics generally occurs after the presentation of motor tics. Tics are classified as being simple or complex and range from mild to severe. Simple tics are defined as sudden, brief, and repetitive movements, while complex tics are distinct, coordinated patterns of movement. 

Simple motor tics include:

  • Eye movements such as blinking
  • Facial grimacing
  • Shoulder shrugging
  • Head or shoulder jerking

Simple vocal tics include:

  • Repetitive throat clearing
  • Sniffing
  • Barking
  • Grunting

Complex motor tics include:

  • Sniffing or touching an object
  • Hopping
  • Jumping
  • Bending
  • Twisting

Complex vocal tics include:

  • Repeating one’s own words or phrases
  • Repeating others’ words or phrases (called echolalia)
  • Using vulgar, obscene, or swear words (called coprolalia)

Tics can be triggered or worsen with excitement or anxiety, or from certain physical experiences (e.g., hearing someone clear their throat or wearing a tight neck collar). As a neurobehavioral disorder, Tourette syndrome is often accompanied by other conditions, including:

  • Attention deficit hyperactivity disorder (ADHD)
  • Obsessive compulsive disorder or behaviors (OCD/OCB)
  • Anxiety
  • Learning disabilities
  • Behavioral issues
  • Problems sleeping
  • Difficulty with social functioning
  • Sensory processing issues

While the cause of Tourette syndrome is unknown, most cases involve the interaction of different genetic variations and environmental factors. Research points to abnormalities in certain regions of the brain, the circuits that connect these regions, and the chemical messengers responsible for communication between nerve cells.

Treatment of Tourette syndrome relies on management of symptoms through medications or behavioral modification or psychotherapy.

Need for research: the Unhide™ Project

Our vision is for brain inflammation disorders to be easily diagnosed by medical professionals and to find accessible therapies. 

To support research in this area we developed the Unhide™ Project, a longitudinal and historical research registry and bio repository platform to study the potential immunological mechanisms driving chronic brain inflammation in order to find new therapeutic targets.

Research is critical to evolve current therapies and develop new treatment targets

The Unhide™ Project was established to collect lab samples from patients with diseases characterized by brain inflammation in order to compare and understand common biomarkers.

You can mail a check (payable to Brain Inflammation Collaborative, Inc.) with your donation any time to the following address:

Brain Inflammation Collaborative, Inc.
925 Genesee St #180440
Delafield, WI 53018