Encephalitis with antibodies to NMDA receptors: a review of current research. Antibodies to the NMDA receptor (autoimmune encephalitis)

In the medical literature, encephalitis refers to a whole group of diseases manifested by inflammatory processes of the brain. The disease has severe symptoms and can have a number of reasons, for example, an autoimmune process that causes anti-receptor encephalitis, or the presence of certain bacteria and viruses. the brain requires immediate qualified treatment, otherwise the risk of irreversible consequences or death is too high. This article will discuss anti-receptor encephalitis.

What is encephalitis?

Encephalitis causes various pathological disorders in the body and lead to the formation of dementia (dementia). The disease can affect not only the brain, but also part of the internal organs and joints.

Pathological conditions can be caused by a number of reasons. According to the factors provoking the disease, the following types of encephalitis are distinguished:

• inflammation caused by infection;
• bacterial or fungal encephalitis;
• a disease provoked by exposure to an organism of a toxic substance;
• autoimmune encephalitis.

The disease affects different parts of the brain. Inflammation can be localized in its cortex, subcortex, or cerebellum. Each type is distinguished by its own signs, symptoms and treatment methods.

What is anti-receptor encephalitis? About it further.

Infectious and bacterial inflammation

Factors causing infectious encephalitis are viruses and bacteria. For example, herpes virus, HIV infection, tuberculosis bacteria, streptococcus and staphylococcus, toxoplasma. In addition, tick-borne encephalitis is a serious problem. This is a viral disease, the distributor of which are some types of ticks. The virus enters the body after an insect bite.

However, with tick-borne encephalitis, the brain is not always affected, in 50% of cases the patient experiences only fever. The disease is also a viral species. It is very dangerous and in most cases it is fatal. This type of encephalitis is characterized by a rapid course, a few days after infection the patient falls into a coma. Herpes encephalitis is fatal in nine out of ten cases; it is practically untreatable.

How does anti-receptor encephalitis manifest? We will tell in more detail.

Autoimmune diseases

There is also a group of encephalitis that is caused in the body. In this case, the patient's own immune cells begin to attack the brain. Diseases of this nature are extremely difficult to treat, cause dementia, lead to impaired brain activity and the peripheral nervous system. In addition to dementia, the disease is accompanied by paralysis and seizures similar to epileptic. For diseases of this kind include, for example, limbic encephalitis. The disease causes an autoimmune response of the body to the presence of cancer cells or a disease of an infectious or viral nature. The rate of development of limbic encephalitis divides the disease into an acute and subacute form. The causes of anti-receptor encephalitis are discussed below.

Acute syndrome

In acute syndrome, the development of the disease occurs rapidly over three to five days. If you do not take urgent measures, then death occurs very quickly. With a subacute course of the disease, the first signs become noticeable after several weeks from the initial moment of development of the pathology. These conditions are characterized by the following symptoms:

• impaired memory;
• cognitive impairment;
• epileptic seizures;
•   (high level of anxiety, depression, agitation);
• behavioral disorders.

In addition, obvious signs are: progressive dementia, sleep disturbances, epileptic seizures with hallucinations. Cases when autoimmune brain lesions are correlated with the presence of cancer are very common. Typically, such encephalitis is caused by lung cancer.

Anti NMDA Receptor Encephalitis

This is an autoimmune disease that affects young women more. In males, pathology is extremely rare. The features of this type of encephalitis include the presence of severe symptoms, which are expressed in serious psychoneurotic changes. That is why these patients are often diagnosed with schizophrenia instead of encephalitis. Women who were diagnosed with this pathology suffered from mental disorders (lack of coherent speech, impaired consciousness).

In addition, a characteristic symptom of anti-receptor encephalitis is a violation of short-term memory and muscle function. For example, in many patients there was an unreasonable contraction of the abdominal muscles, as well as jerky movements of the legs or arms.

About half of the examined patients had ovarian cancer. However, there may be cases when the patient does not have oncology. Moreover, there have been cases of the diagnosis of anti-receptor encephalitis in children not suffering from such diseases. Antibodies associated with certain brain structures called NMDA receptors spontaneously appear and begin to develop actively in them. Antibodies are fixed and block receptors, which in turn causes mental disorders, motor disorders and epileptic seizures. All this indicates that in many cases, doctors can not determine the exact cause of the disease. It should be noted that, in principle, they managed to identify this disease and learned to diagnose it no more than ten years ago. Symptoms and treatment of anti-receptor encephalitis are interrelated.

Diagnostics

An experienced doctor who is not the first time encounters such pathologies will have suspicions even at the stage of examination of the patient. To make an accurate diagnosis, additional research is needed. As a rule, the appointment of magnetic resonance imaging is completely justified here. MRI will confirm or refute suspicions of inflammatory processes in the brain, however, it will not help to identify the cause of the disease.

For autoimmune diseases, including suspected anti-receptor encephalitis (we examined the causes of the disease), we analyze the presence of antibodies to the NMDA receptor. In some situations, cerebrospinal fluid analysis and a brain biopsy are prescribed. A biopsy is prescribed only as a last resort, when other methods to identify the cause of the disease are not informative. In this case, you can not do without consulting an oncologist.

Possible complications

Autoimmune diseases are difficult to diagnose, therefore, in the absence of proper experience with the doctor, the patient may be in a psychiatric clinic due to an incorrect diagnosis. The lack of necessary treatment leads to psychiatric abnormalities, which are often irreversible. In addition, there is a high probability that the patient may fall into a coma. If the patient does not take the medications necessary for treatment, the vegetative state develops very quickly, and in a third of patients

Treatment for anti-receptor encephalitis

To make a correct diagnosis, first of all, the patient is sent for examination and consultation to a neurologist. The disease is diagnosed in the presence of certain antibodies in the blood. To exclude an incorrect diagnosis, an oncologist examination is also required. With timely treatment and a well-structured oncological treatment, in most cases it is possible to achieve persistent and prolonged remission. Good results are also achieved with immunomodulators. But this type of treatment is available only if the suspicion of oncology turned out to be baseless.

To reduce psychiatric symptoms, patients are prescribed drugs with a sedative effect. They calm and normalize sleep. With the appearance and repeated recurrence of seizures, antispasmodic drugs are prescribed. Removal of acute inflammation is achieved using corticosteroids. They are administered intramuscularly, and the duration of the course of treatment is prescribed by the doctor.

Anti-prescription encephalitis is practically not completely cured. Treatment helps stop the further progression of the disease and eliminates the development of neurological disorders. If the disease was caused by oncology, then the elimination of the tumor gives a very stable result, and 70% of patients recover completely. How can brain anti-receptor encephalitis be prevented?

Prevention

Since childhood, we know that you need to go to the forest in closed clothing, which excludes ticks from exposed skin. Such measures help in the prevention of viral and bacterial encephalitis. It is also important to contact medical institutions in a timely manner and follow the instructions of doctors. As for brain diseases of an autoimmune nature, including anti-prescription encephalitis, it is impossible to prevent the development of such pathologies.

Conclusion

According to available data, almost half of patients suffering from anti-receptor encephalitis fully recover. A third of patients have mild residual effects, and a small proportion of patients suffer from serious complications. About 10% of patients died.

Therefore, we must once again emphasize that when a tumor is detected at an early stage and its removal, body functions are restored in full, that is, recovery occurs. All this allows us to conclude that it is necessary to consult a doctor at the first symptoms of the disease in order to increase the chance of a successful outcome.

Anti NMDA Receptor Encephalitis   , also known as encephalitis antibody NMDA receptor   , is an acute form of inflammation of the brain that is potentially fatal, but has a high probability of recovery after treatment.

This is caused by an attack on the immune system, primarily targeting the NR1 subunit of the NMDA receptor (N-methyl-D-aspartate). The condition is associated with tumors, mainly teratomas of these ovaries. However, many cases are not related to malignant tumors.

The disease was officially classified and named by Josep Dalmau and his colleagues in 2007.

Before developing a complex of symptoms that are specific for anti-NMDA receptor encephalitis, people may experience prodromal manifestations, including headaches, flu-like illness, or notice upper respiratory infections. They become noticeable within weeks or months before the onset of the development of pathology. In addition to prodromal symptoms, the disease progresses with various indicators, and patients may exhibit neurological dysfunctions. At the initial stage of development, the symptoms are different between children and adults.

However, behavioral changes are a common first sign in both groups. They often are paranoia, psychosis. Other common manifestations include cramps and bizarre movements, mainly of the lips and mouth, but also strange pedal movements with legs or arms resembling a piano. Some other symptoms characteristic of the onset of the disease include cognitive impairment, memory deficits, and speech problems (aphasia, persistence, or mutism).

Symptoms usually manifest themselves in psychiatric practice, which can lead to a differential diagnosis. In many cases, this makes diagnosis impossible. As the disease progresses, the symptoms become medically urgent and often include autonomic dysfunction, hypoventilation, cerebral ataxia, hemiparesis, loss of consciousness, or catatonia.

During this acute phase, most patients require treatment in the intensive care unit to stabilize breathing, heart rate and blood pressure. Loss of feeling on one side of the body can be a symptom. A distinctive feature of anti-NMDA receptor encephalitis is the simultaneous presence of many of the manifestations listed above. Most patients experience at least four symptoms, others six or seven during the course of the illness.

Pathophysiology

The condition is mediated by antibodies that target the NMDA receptors in the brain. They can be obtained by cross-reactivity with NMDA receptors in teratomas that contain many types of cells, including brain cells, and thus represent a window in which the breakdown of immunological tolerance can occur. Other autoimmune mechanisms are suspected in patients who have no tumors. While the exact pathophysiology of the disease is still under discussion. An empirical assessment of the origin of anti-NMDA antibodies in serum and cerebrospinal fluid leads to consideration of two possible mechanisms.

Some of them can be determined by simple observations. Serum NMDA receptor antibodies are sequentially detected at higher concentrations than antibodies to cerebrospinal fluid, an average of ten times higher. This strongly indicates that antibody production is a systemic and not a brain or cerebrospinal fluid. When concentrations normalize for total IgG, intrathecal synthesis is detected. This means that there are more NMDA receptor antibodies in the cerebrospinal fluid than would be predicted based on the expected amounts of total IgG.

1. Passive access involves the diffusion of antibodies from the blood through a pathologically impaired blood-brain barrier (GBS). This cell filter, which separates the central nervous system from the circulatory system, usually prevents large molecules from entering the brain. Various causes have been proposed for such a collapse of integrity, with the most likely response being acute inflammation of the nervous system. Similarly, it was shown that the participation of the hormone-releasing corticotropin in mast cells during acute stress contributes to the penetration of OGB. However, it is also possible that autonomic dysfunction, which manifests itself in many patients in the late stages of the disease, contributes to the introduction of antibodies. For example, an increase in blood pressure will cause large proteins to be extravasated into the cerebrospinal fluid.
2. A possible mechanism is also intrathecal production. Pharmaceutical company Dalmau et al. showed that 53 out of 58 patients with the condition had at least partially retained GBS, with a high concentration of antibodies in the cerebrospinal fluid. In addition, cyclophosphamide and rituximab, drugs used to eliminate dysfunctional immune cells, were a successful treatment in the second line of patients where therapy failed. They destroy excess antibody-producing cells, thus alleviating the symptoms.

A complex analysis of the processes associated with the presence of antibodies in the cerebrospinal fluid hints at the combination of these two mechanisms in tandem.

NMDA Receptor Antibodies

As soon as antibodies enter the CSF, they bind to the NR1 subunit of the NMDA receptor. There are three possible methods in which neuron damage occurs.

1. Decreased density of NMDA receptors on the postsynaptic handle due to receptor internalization after antibody binding.
2. Direct antagonism of the NMDA receptor, similar to the action of typical pharmacological receptor blockers, such as phencyclidine and ketamine.
3. Recruitment of the complement cascade through the classical pathway (antibody-antigen interaction). The membrane attack complex is one of the end products of this cascade and can be inserted into neurons as a molecular cylinder, allowing water to penetrate. Then the cell is lysed. It is noteworthy that this mechanism is unlikely, since it causes the neuron to die, which is incompatible with existing evidence.

Diagnostics

First of all, this is a high level of clinical suspicion, especially in young people who exhibit abnormal behavior, as well as autonomic instability. A change in the level of sensom and seizures in the early stages of the disease. Clinical examination may additionally reveal delusions and hallucinations

Treatment

If people have a tumor, a long-term prognosis is usually better, and the likelihood of relapse is much lower. This is due to the fact that the tumor can be removed surgically, thereby eradicating the source of autoantibodies. In general, early diagnosis and aggressive treatment are believed to improve patient outcomes, but this cannot be known without data from randomized controlled trials. Given that most patients are initially accepted by psychiatrists, it is imperative that all doctors consider NMDA receptor encephalitis as a possible cause of acute psychosis in young patients who have no past neuropsychiatric history.

• If a tumor is detected, its removal should occur in combination with first-line immunotherapy. Includes steroids, intravenous immunoglobulin and plasmapheresis for the physical removal of autoantibodies. A study of 577 patients showed that over four weeks, about half of them felt better after taking the drugs.
• Second-line immunotherapy includes rituximab, a monoclonal antibody that targets the CD20 receptor on the surface of B cells, thereby destroying self-reactive ones. Cyclophosphamide, an alkylating agent that cross-links DNA, is used to treat both cancer and autoimmune diseases.
• Other medicines, such as alemtuzumab, remain experimental.

Forecast

The recovery process from encephalitis against NMDA can take many months. Symptoms appear in the reverse order and the condition of the patients is gradually improving.

Epidemiology

The number of new diseases per year is unknown. According to the California encephalitis project, the largest series of cases to date characterizes 577 patients with antimesodiagnostic encephalitis. The study provides the best approximation of the distribution of diseases. It was found that women are disproportionately affected - 81%. Pathology begins in children under the age of 21 g. Only 5% of cases were older than 45 years. The same survey showed that 394 out of 501 people (79%) had good results, 30 patients (6%) died by 24 months, and the rest remained with mild and severe deficiency. The study also confirmed that patients are more often of Asian or African descent.

Society and Culture

Symptoms of pathology are the main cause of historical tales of demonic possession of patients.

Reporter from   New york city   Suzanne Kahalan wrote a book called "   Brain on Fire: My Month of Madness about her illness experience.

Dallas Cowboys protective lineman Amobi Okoye spent 17 months. anti-NMDA encephalitis receptor. In addition to three months in a coma caused by medicine, he experienced a 145-day memory gap and lost 78 pounds. He returned to practice on October 23, 2014.

Knut, a polar bear in the Berlin Zoological Garden who passed away on March 19, 2011, was diagnosed with anti-NMDA receptor encephalitis in August 2015. This is the first case discovered outside the human body.

I recently compared the actions of Roskomnadzor to block Telegram with an autoimmune disease: “Having recognized the imaginary terrorist threat, he went to fight with all the healthy tissues of the Internet.” Many wrote in the comments: “Lupus!” But no, this is not lupus. It is time to make a differential diagnosis and expand the biological metaphor of what is happening.

The lupus, so beloved by Dr. House's team, manifests itself in the form of a rash on the face, but in general it is a disease of connective tissue and its derivatives. If we imagine that people living in the country are the cells of a single organism, working collectively for its prosperity, then lupus is more likely when they infringe on the rights of truckers, fill people with garbage and do not repair roads.

The Internet is a fiber of the country's nervous system. Therefore, massive blocking of sites should be considered autoimmune encephalitis. The disease is characterized by inflammation of the brain and the appearance of antibodies to molecules located on the surface of nerve cells. First of all, these are various neurotransmitter receptors. They are blocked by antibodies, like websites by IP addresses: in our country, the titer of such antibodies has already exceeded 18 million.

Since receptors of the same type are present in many nerve cells (only one cannot be blocked), the latter fail in groups. Please note that this is exactly what Roskomposor does!

Depending on which particular molecules become victims of a malfunctioning immune system, different variants of autoimmune encephalitis are observed. Each has its own set of symptoms, including psychiatric ones.

For example, we do not see the muscle stiffness syndrome characteristic of autoimmune encephalitis, with damage to GABA-A receptors or glycine, or movement disorders associated with damage to dopamine receptors. But one diagnosis fits perfectly.

The most common variant of autoimmune encephalitis is anti-NMDA receptor encephalitis (later we will return to what NMDA means). Psychiatric syndromes with NMDA receptor encephalitis include (I do not invent anything, everything is taken in the order indicated in the scientific publication):

1. Delusions of grandeur;
2. Paranoid delirium;
3. Hallucinations - sound and visual;
4. Unusual behavior;
5. Anxiety;
6. Fear;
7. Insomnia;
8. Confusion;
9. Loss of memory.

What, if not the paranoid delusions with hallucinations, is the round-the-clock search for fictional terrorists on Telegram? What, if not memory loss, blocking sites that store scientific and other valuable information, increasing censorship of the Internet? What, if not delirium of grandeur, ignoring the interests of millions of Telegram users and numerous organizations whose sites have laid down due to carpet locks? What, if not confusion, a denial of the absurdity of what is happening?

Coincidence? I don’t think so!

The symptoms of anti-NMDA receptor encephalitis are treated with immunosuppressants. That is, it is worth suppressing the activity of Roskomnadzor, recognizing that it is hyperactive. But, alas, everything is not so simple.

Everything is well provided for in the human body. Our brain is protected from the immune system - including the blood-brain barrier (in the metaphor with the Internet, anonymizers, Tor, VPN are trying to perform its function). Because for survival it is very important that nothing interferes with the transmission of information.

Therefore, autoimmune encephalitis is very rare. And, as a rule, they arise not just like that, but against the background of a tumor. In the case of anti-NMDA receptor encephalitis, it is usually ovarian teratoma (which makes sense, because Russia is female). Immature teratomas can sprout into nearby tissues and produce metastases.

The key characteristics of cancer cells are:

1. Violations of programmed cell death. In other words, the lack of cell turnover;
2. Violations of the control of the cell cycle;
3. Unjustified intake of glucose and other nutrients. Something like intercellular corruption. Together with offers to all other cells to tighten belts.

And again, all the signs are there. It is because of a corrupt tumor that the immune system does not solve real problems (for example, fire safety in shopping centers), but deals with inflammation of the brain. By the way, the NMDA receptor is a glutamate receptor. Therefore, it is not surprising that the deputies are very actively fighting this substance.

So, the final diagnosis: anti-NMDA receptor encephalitis in the presence of immature metastatic ovarian teratoma. Necessary tumor removal. Steroids to suppress the immune system. Intravenous immunoglobulin. Plasmophoresis to eliminate autoreactive antibodies. The main thing is that they do not have time to ban the import of drugs.

It remains to say that each of us can plant steroids

Suzanne was only 24. She had just begun the first serious relationship in her life, she got a job at the newspaper The New York Post. And suddenly life threw the girl a difficult test. It all started with the fact that she began to feel like bugs were biting her. Then they began to suffer migraine attacks, insomnia, apathy, fatigue appeared. When an inexplicable feeling of anxiety came over Susanna, she realized that something was wrong with her. A gynecologist advised her to contact a neurologist ... when she heard that her hand was numb.

The same picture that helped the doctor make an accurate diagnosis

Before finding out the correct diagnosis, Suzanne had to undergo many examinations.During this time, she was tormented by attacks that she herself did not remember, but restored from the stories of her relatives and her boyfriend. One doctor considered her ailment to be Pfeiffer’s disease (infectious mononucleosis), the other as meningitis, the third decided that the patient was abusing alcohol, the fourth suggested bipolar disorder. Fortunately, one of the neurologists came up with an unexpected thought: Dr. Suhel Najar offers the patient a drawing test, which is usually passed by those who suggest a stroke or Alzheimer's disease.

Suzanne draws a weird dial   - all 12 digits on it are located on the right side, and the left is empty. This is a sign of inflammation in the right hemisphere of the brain, which is responsible for what we see on the left. So it turns out that her disease is not mental, but autoimmune (anti-NMDA receptor encephalitis). Her brain is attacked by her own immune system. A timely diagnosis saved the life of Susanna.

I rushed to the bed and turned on the phone: it turned out two hours had passed! And it feels like no more than five minutes. After a couple of seconds, a migraine pierced his head again; made me sick. It was then that I first noticed that something was wrong with my left hand: the tingling sensation, as with numbness, was just too strong.   I clenched and unclenched my fist, trying to get rid of the "needles", but it only got worse.   Then, trying to ignore the tingling sensation, I rushed to the chest of drawers to remove Stephen's things - so that he would not notice that I was rummaging through them. But soon the left hand was completely numb.

Suzanne Cahalan

“When the doctor saw the result of my test,   he almost laughed with relief, Susanna recalls. “Our cerebral hemispheres control the body crosswise, the right hemisphere is responsible for what you see on the left.” Half of the dial was evidence of inflammation in the right hemisphere of my brain. It also indicated that I was at the wrong place: the psychiatry department was primarily a place where they struggled with symptoms with heavy drugs. Further research showed that I have an autoimmune disease in which my own body attacks my brain. Scientists first wrote about my version of anti-NMDA receptor encephalitis in 2005. So I got sick a couple of years earlier, and everything could have been otherwise ... "

Excerpt from the book “Mind on Fire. The month of my madness

I woke him with strange dull groans, the sounds of a working TV mixed in with them. At first he thought that I was grinding my teeth, but then, when the gnashing turned into a high-frequency screech (like sandpaper for metal) and a dull moo, similar to what the mentally ill make, I realized that something was wrong. He decided that I couldn’t fall asleep, but when I turned around, I saw that I was sitting on the bed with my eyes open - an invisible look, the pupils were dilated ... I suddenly started waving my arms in front of me, like a mummy; his eyes rolled back and his body tightened. Foam and blood poured from his mouth through gritted teeth. I still don’t remember this fit - however, like all the subsequent ones.

A long (more than a year) and expensive treatment begins. It ends with a full recovery. She doesn't even need to take medicine anymore.

But that month of her life, which she spent in a psychiatric clinic, completely disappeared from her memory.   She tries to fill this gap by talking with doctors and relatives, looking at medical reports and videos made at the clinic. She sees herself in a state of insanity: she cries lying in bed, trying to tear electrodes from her head. She recalls how she found in her hands the bites of a bed bug, which actually was not.

It seemed to her that her father was a killerthat she, if she so wishes, can age other people, that the pages of newspapers and the walls of the room breathe ...

Suzanne is lucky - only 10% patients, according to Suhel Najar, get the correct diagnosis. Those who fell ill before 2005, when this disease was first described, had no chance at all. “If I got sick a couple of years earlier, I could spend my whole life in a psychiatric clinic or even die. A thin line separated me from this, ”says Susanna Kahalan in an interview 1.

Excerpt from the book “Mind on Fire. The month of my madness

It turned out that, in addition to the strongest tonic-clonic seizure, I also experienced several partial seizures with various symptoms. The reason was excessive stimulation of the temporal lobes of the large brain - the part of the brain most prone to irritation. Symptoms of such a seizure can be high spirits, like Christmas morning, sexual arousal, or experiences that are mistaken for a religious or mystical one. Some patients report a sense of deja vu and its opposite - jameu, when everything around seems unfamiliar. Someone sees the halo of light, another begins to see the world strangely disproportionate (the syndrome is called the "Alice effect in Wonderland") - this happened to me when I went to meet with John Walsh.

After recovering, Susanna decided to restore everything that happened to her and write a book,   to spread the word about his rare illness. Her story has saved more than one life, it turned out that this disease affects young girls and women from 12 to 45 years old.

  For example, american sophomore   named Emily suddenly behaved strangely. It seemed to her that the vans were chasing her, and the doctors were not doctors at all, but actors. The girl ended up in a psychiatric ward, in which her parents were recommended to apply for a disability pension for her daughter. But the girl’s father heard the story of Suzanne Kahalan and showed the neurologist an article about her. Emily had the same illness. After a year, she was already healthy, although before that she had traveled in a wheelchair.

Anti-NMDA receptor disease   Encephalitis annually affects only 30-35 patients in the Netherlands. Given other types of diseases in which the body's immune system attacks its own brain, this is about a hundred patients per year.

Excerpt from the book “Mind on Fire. The month of my madness

No one knows why some people - especially those who do not have teratomas - develop anti-NMDA receptor encephalitis. There is no basic understanding of what triggers the disease. We don’t know what factors influence the development of the disease more strongly - the external environment or a genetic predisposition ... But doctors believe that the most likely cause of the disease was a combination of external influences - contact with the sneezed, contraceptives, toxic substances in the apartment - and genetic predisposition to the development of an aggressive type of antibody. Unfortunately, because it is so difficult to find out the real cause of the disease, prevention may be the main goal of doctors; focusing on early diagnosis and quick treatment is much more realistic.

Today it is already known that a disease discovered recentlyare most often affected by young women. In half of the cases, the cause of the disorder is unknown; in the other half of the cases, it is associated with a benign ovarian tumor. Antibodies see the tumor as something foreign to the body and begin to attack. When antibodies do it too fanatically, and also attack areas where they should not be, then we are talking about an autoimmune disease.

Symptoms of this disease: sudden onset of psychosis and seizures.   in the complete absence of such complaints, earlier or strange movements with the mouth or hands. Doctors take the cerebrospinal fluid and examine it for antibodies. Such a test with 100% certainty allows you to establish the presence or absence of anti-NMDA receptor encephalitis. Without therapy, the course of the disease is negative. About 2/3 of patients die or settle in care homes for the rest of their lives. The disease is treatable. However, it costs a lot of money.

Suzanne and her husband Stephen on their wedding day in 2015

This disease is unique.   in comparison with other types of fatal encephalitis and autoimmune diseases, fraught with disability for life. Indeed, it is difficult to recall another disease in which the patient may be in a coma and even die and spend several months in the intensive care unit, and then recover completely - or almost completely.

In the case of Suzanne Kahalan, the treatment cost a million dollars. But in Europe it costs several times less. With the help of aggressive drugs, the body’s own immune system is “slowed down”. Or they filter the patient’s blood and remove unnecessary substances from it. Such therapy returns 80% of patients home and ultimately leads to a complete recovery. For treatment, it is necessary to spend several times under a dropper for about a week.

Based on its story   and her diary entries, Suzanne wrote the book Mind on Fire: A Month of Madness. In 2016, a film was made from the book with Chloe Moretz in the title role. Charlize Theron became the producer of the picture.

Suzanne todaywrites articles, maintains a blog, helps everyone who is faced with a similar diagnosis. She recently married her boyfriend, who supported her during her illness.

Website   Suzanne   susannahcahalan.com

You can order a book at   website   eksmo.ru

1 S. Kahalan “Mind on Fire. The month of my madness ”(Eksmo, 2016).

Encephalitis associated with autoaggression of the immune system is not fully understood. This is a rather serious disease - inflammation of the very substance of the brain. It has been proven precisely that its development is associated with the development in the body of antibodies to receptors of its own nerve cells (neurons) located in different parts of the brain.

Causes of the disease

The first cases of this type of encephalitis were detected in women with ovarian tumors. Therefore, encephalitis was regarded as paraneoplastic, that is, developing with a malignant tumor.

Indeed, in many cases, encephalitis precedes a cancerous tumor (sometimes for several months and even years), and often develops already against the background of a malignant disease.

Scientists have managed to identify almost 30 antigens associated with the development of malignant processes in the body and associated with damage to nerve cells. A malignant tumor is detected in 60% of patients with clinical manifestations of encephalitis.

But in some cases, the neoplastic process is not detected, and encephalitis as a result of a malfunction in the immune system develops for some reason. And what causes the immune system to produce antibodies against CNS own nerve cells is not yet clear.

Typical manifestations of encephalitis in pediatric patients in many cases are not associated with any tumor. Antibodies in completely healthy children of different ages are produced spontaneously and also bind to the NMDA receptors of nerve cells in the brain.

By blocking these receptors, antibodies lead to the slow development of mental disorders, motor disorders and seizures.

These data confirm that many mechanisms leading to autoaggression and synthesis of antibodies to NMDA receptors of brain cells, to neuroimmune conflict, have not been studied, have not been established.

Epidemiology

Mostly women are affected, in men this type of encephalitis develops in isolated cases. The disease develops in youth, the average age of patients is about 25 years. About 40% of cases are teenagers under 18 years of age. It was noted that in male patients and at a younger age, encephalitis develops more often without a malignant neoplasm.

The role of autoimmune antibodies

The importance of antireceptor antibodies in the development of encephalitis is conclusively proved by the following data:

1. In each case of encephalitis antibodies   to NMDA receptors of brain cells were found in the acute period of the disease in cerebrospinal fluid and blood serum. Moreover, a decrease in the titer of these antibodies was noted in the stage of recovery and recovery. In addition, there was a clear relationship between the number of antibodies and the outcome of the disease.
2. Preparations Keiamin,   Phencyclidine and others in the NMDA receptor antagonist group can cause symptoms that are similar to the symptoms of this encephalitis.
3. In most cases, patients with anti-NMDA receptor encephalitis develop central hypoventilation.   This can be linked to the fact that the targets for autoimmune antibodies are neurons located mainly in the forebrain, which is affected by anti-NMDA receptor encephalitis. This leads to respiratory disorders.
4. Hyperkinesis   manifested with this encephalitis are not associated with epilepsy. Proof of this is that sedatives and antiepileptic drugs are not effective. This is confirmed by the results of electroencephalographic observations of such patients.
5. In each case, encephalitis was excluded viral infection,   as the cause of damage to brain matter: the results of the study of cerebrospinal fluid, blood, intravital biopsy of the brain substance and pathological analyzes did not detect viral markers.

Summarizing these facts and the results of numerous studies in patients, we can no doubt confirm the leading role of autoimmune aggression in the mechanism of development of anti-NMDA receptor encephalitis.

Clinical symptoms

The disease develops slowly at any age of the patient.

In its development, several stages are distinguished.

Prodromal symptoms

Not manifested in all patients (86% of patients), this period lasts about 5 days.

The prodromal stage is characterized by nonspecific manifestations resembling symptoms of SARS:

• headache;
• temperature rise;
• weakness.

Psychotic stage of the disease

It manifests itself as psychopathological behavioral disorders, which prompts the relatives of patients to seek help from a psychiatrist. But even a doctor can suspect organic brain damage in this period of the disease. Typical symptoms are:

• minimization emotional   manifestations (patients are lethargic, withdrawn into themselves, depression is often noted);
• decline congruent   skills - the ability to process information coming from outside: short-term memory, the ability to use the phone and other devices, etc .;
• schizophrenic   symptoms: delirium, hallucinations (auditory and visual), compulsive behavior (repeated obsessive actions as a result of an irresistible desire), a decrease in the critical assessment of one’s condition;
• disorders of memory   (amnesia) and speech are more rare;
• violation sleep

The duration of this stage is about 2 weeks. Attacks of seizures indicate the progress of the disease.

Areactive stage of encephalitis

It manifests itself as a violation of consciousness, resembling catatonia (motor disorders in the form of a stupor or arousal). At the same time, patients in the stage of excitement automatically repeat other people's words and phrases, make sweeping movements, are distinguished by foolishness, laugh unreasonably.

It is often noted:

• mutism   (the patient does not make contact, does not answer questions and does not fulfill requests and commands);
• akinesia   (impossibility of active, arbitrary movements);
• atetoid   movements (fanciful movements of limbs or fingers, often repeated flexion-extension, unnatural postures, etc.);
• cataleptic   symptoms (decreased sensitivity to external stimuli);
• paradoxical   phenomena (for example, there is no reaction to a pain stimulus).

Hyperkinetic stage

Manifested by the gradual development of hyperkinesis. Hyperkinesis can have different localization and speed, similar to psychogenic reactions.

It can be:

• oro-lingual dyskinesias (prolonged chewing movements, licking the lips, impaired opening of the mouth, excessive compression of the teeth);
• movements of limbs and fingers;
• abduction or reduction of eyeballs, etc.

At this stage, signs of autonomic disturbances are noted in the form of increased or decreased heart rate, fluctuations in blood pressure, fever, and excessive sweating. Of particular danger are respiratory disorders, which sometimes require resuscitation. Hypoventilation and hemodynamic disorders develop in all patients.

Symptom regression stage - long stage

The reverse development of manifestations occurs within 2 months, but hyperkinesis can regress for more than 6 months, and be resistant to ongoing therapy. Along with the elimination of hyperkinesis, the psychosomatic status of the patient improves. All patients are characterized by persistent amnesia about the condition.

Diagnosis of anti NMDA receptor encephalitis

In the presence of clinical manifestations characteristic of encephalitis, laboratory and hardware diagnostic methods can be used to confirm the autoimmune nature of the disease.

Laboratory methods include:

1. Study   cerebrospinal fluid (cerebrospinal fluid). Clinical analysis will give a moderately pronounced increase in the number of cells due to lymphocytes (up to 480 cells / ml), an increase in protein levels (within 49-213 mg / ml). Such changes are not specific, but they are observed in all patients with anti-NMDA receptor encephalitis.
2. Serological   blood and cerebrospinal fluid tests. Allows you to get a specific test confirming the diagnosis - reveals antibodies to NMDA receptors. Moreover, the higher the titer of antibodies, the more severe neurological disorders. Antibody titers in cerebrospinal fluid are higher than in blood. In a dynamic study, titers decrease in patients with recovery, and in the absence of an effect in the treatment, the level of specific antibodies remains high in the blood and cerebrospinal fluid.
3. Immunological   cerebrospinal fluid analysis. Shows an increase in class G immunoglobulins.
4. Virological   studies of any biosubstrate give a negative result.

Hardware diagnostic methods:

1. MRI   carried out in standard mode or with contrast (the introduction of gadolinium), according to experts, most often does not detect changes. When conducting a study in the FLAIR mode, some patients may have focal signal amplification in the temporal lobes, less often in the brain stem. Upon recovery, these changes disappear.
2. Positron emission tomography with fluorodeoxyglucose (SPECT and FDG-PET), according to experts, in some cases it can reveal an accumulation of contrast in the motor zones with the manifestation of dyskinesia (no accumulation is noted in recovery), hypoperfusion (insufficient blood supply) in the frontotemporal temporal regions of the cerebral cortex.
3. EEG   (electroencephalography) in the reactive and hyperkinetic stages of encephalitis reveals diffuse (but with a predominance of lobewise) d- and q-activity.

In the clinical manifestations of anti-NMDA receptor encephalitis, the maximum possible examination must be carried out to identify the oncopathology of any organs and systems, including children. Oncological screening is an important component of the diagnostic algorithm for such encephalitis.

Treatment

Treatment of patients should be carried out in a resuscitation unit, taking into account the likelihood of developing hemodynamic and respiratory disorders. Comprehensive treatment should include pathogenetic and symptomatic therapy.

As a pathogenetic therapy, antiviral drugs (Acyclovir) are treated until the results of the study exclude the viral nature of encephalitis.

It is very important to conduct an examination in terms of cancer monitoring as soon as possible: the sooner the radical treatment of cancer is carried out, the easier and faster it will be possible to cope with the treatment of encephalitis.

To suppress the synthesis of specific antibodies are used:

• corticosteroid drugs (methylprednisolone);
• immunoglobulins (for intravenous administration);
• monoclonal antibodies (rituximab);
• plasmapheresis (purification of blood from harmful substances by passing it through special filters);
• cytostatics (Azathioprine, Cyclophosphamide) in rare cases.

As a symptomatic treatment, the following are used:

• anticonvulsants (phenobarbital, clobazam, phenytoin, clonazepam, etc.) with the development of convulsive seizures;
• with dyskinesias, antipsychotics are prescribed and, in addition, Midazolam, Propofol.

Disease outcomes

The average duration of inpatient treatment is 2.5 months. Of the residual neuropsychiatric manifestations after discharge, every fifth patient has sleep disturbances, 85% may have symptoms of frontal lobe dysfunction:

• impulsiveness;
• incontinence;
• planning difficulties;
• attenuation of attention, etc.

According to statistics, complete cure for adult patients occurs in 47% of cases. With mild but persistent residual changes, treatment ends in 28% of patients. In 18% of patients, more severe manifestations remain. In 7% of cases, a fatal outcome was noted.

Paraneoplastic encephalitis is associated with the formation in the body of antibodies to NMDA receptors of brain nerve cells. Psychopathological disorders often lead to hospitalization of patients in a psychiatric hospital.

The sooner paraneoplastic encephalitis is suspected and the correct diagnosis is made, an examination is carried out to identify oncopathology and its radical treatment in case of detection, the more effective the patient's treatment will be and the more chances of recovery.