Anti-receptor encephalitis: what is this disease and how to treat it

Reasons for development

Encephalitis develops as a result of inflammation caused by infections of various natures. The disease can also be triggered by poisoning the body with toxic substances. Encephalitis is diagnosed in rare cases. The main cause of development is viral infections that affect the brain. In 37-50% of cases they have an unknown etiology.

NMDA receptors are a collection of neuron endings, without which it is impossible to conduct nerve impulses and, as a result, remember information. These nodules are also involved in the mechanism of pain formation and other processes of brain activity.

A significant proportion of brain damage is occupied by autoimmune encephalitis (we talked about them earlier). In such conditions, the body produces antibodies that attack its nerve cells. Abnormal brain changes lead to memory loss, psychotic disorders and behavioral disorders.

Anti-NMDA receptor encephalitis affects different areas of the brain. Inflammation is localized in the cerebellum or cortical structures. Each type of disease is characterized by certain clinical manifestations, symptoms and treatment methods.

In the medical literature, there are more than 500 case reports of patients with established anti-NMDA receptor encephalitis. This condition is common among patients aged 21-35 years, of which 20% are men and 80% are women. In 4.2% of all types of disease of unknown origin, pathological processes develop against the background of chickenpox, herpetic and enteroviral encephalitis.

In half of adult patients, the cause of pathological changes is ovarian teratoma - a tumor with cells atypical for a given tissue. Antibodies begin to fight the foreign tumor too intensely, which leads to their spread to other areas. Treatment is carried out surgically - the uterus with appendages or ovaries are removed. Immunosuppression (immune suppression) helps reduce the number of antibodies. However, even with successful treatment, relapses may occur.

Classification and symptoms of encephalitis

Encephalitis is a large group of diseases manifested by an inflammatory process in the brain.
They cause various pathological changes in the body and lead to the development of dementia (dementia). The disease can affect not only the brain, but also internal organs and joints. Pathology can be caused by a number of factors. Based on the reason that provokes the development of the disease, the following types of pathology are distinguished:

• inflammation of an infectious nature;
• bacterial or fungal encephalitis;
• disease caused by toxic effects on the body;
• encephalitis of autoimmune nature.

The disease affects different parts of the brain. The inflammatory process can be localized in the cerebral cortex, subcortical nuclei or cerebellum.

Each type has its own signs and symptoms, as well as treatment methods.

The role of autoimmune antibodies

Antireceptor antibodies have an important role in the development of the disease:

• Antibodies to NMDA receptors were detected after examining the patient in the acute phase of the disease. With a decrease in the number of antibodies, regression of symptoms and recovery were observed.
• Medications such as Phenclidine and Keyamine cause manifestations similar to the clinical picture of encephalitis.
• Often, patients with this diagnosis experience central hypoventilation - a violation of autonomic respiratory control. The main target of attack for antibodies is the nerve cells of the forebrain, which are damaged during encephalitis. As a result, a person develops abnormalities in the functioning of the respiratory system.
• Hyperkinesis is an involuntary movement that is in no way associated with epileptic seizures. This is easy to prove by using sedatives to eliminate the symptom - they are ineffective for encephalitis.
• A viral infection can serve as a provoking factor for the disease, but is not its cause. Based on the results of a blood and cerebrospinal fluid examination, as well as a biopsy of brain tissue, no viral markers were detected.

Summarizing these data, it can be argued that the leading role in the mechanism of progression of anti-NMDA receptor brain damage is assigned to autoimmune aggression.

Acute syndrome

In acute syndrome, the disease develops rapidly over three to five days. If urgent measures are not taken, death occurs very quickly. In the 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:

• memory impairment;
• cognitive disorders;
• epileptic seizures;
• mental disorders (high level of anxiety, depressive states, agitation);
• behavioral disorders.

In addition, obvious signs are: progressive dementia, sleep disturbances, epileptic seizures with hallucinations. It is not uncommon for autoimmune brain lesions to be correlated with the presence of cancer. Typically, such encephalitis is caused by lung cancer.

Symptoms of anti-NMDA receptor encephalitis

Clinical signs of encephalitis with antibodies to NMDA receptors have been established based on studies of patients with an elucidated etiology of the disease. Based on the examination results, the following stages of the pathological process were established:

1. Prodromal. The patient suffers from fatigue, headaches, and fever. The duration of the phase is 5 weeks.
2. Psychotic. When moving to this stage, psychopathic symptoms appear - a state of apathy, depression, fear and withdrawal. Cognitive (cognitive) functions also decrease - the inability to remember recent events, difficulties in using everyday things, symptoms of schizophrenia - delusions, decreased criticism of one’s own condition, hallucinations. Memory impairments at the psychotic stage are rare - in 25% of patients.
3. Areactive. The phase begins 2 weeks after the onset of psychotic symptoms. Most patients (70%) experience seizures. There are signs of impaired consciousness. They manifest themselves in mutism (the patient does not respond to questions and actions in his direction), akinesia (lack of motor activity). Most patients make a forced grimace, resembling a smile.
4. Hyperkinetic. Clinical manifestations of this phase develop gradually. The patient licks his lips and performs chewing movements. He can protrude his pelvis, raise his shoulders, and perform twisting movements. Blood pressure is constantly changing, and symptoms such as sweating and redness of the skin are observed.
5. Gradual regression phase. The stage of reverse development of symptoms leads to increased control of one's own movements. The regression lasts 2 months. In some cases, the process is delayed for six months. The person develops memory loss for current events.

When the first symptoms appear, it is important to undergo an examination - early detection of the disease will allow you to fully recover without consequences or complications.

Diagnostics

When diagnosing the described brain damage, a specialist assumes a certain type of disease. The typical patient is a young woman with signs of emotional distress and cognitive impairment.

Diseases that are considered along with encephalitis include:

• epilepsy;
• metabolic (metabolism-related) and toxic disorders of the brain;
• focal brain damage.

Encephalitis is an altered mental state in which there is at least one of these signs - fever, seizures, changes in EEG (electroencephalography) and MRI.

If there is a possibility of encephalitis, the patient is prescribed a lumbar puncture (sampling of cerebrospinal fluid through a lumbar puncture), contrast MRI (with the introduction of a contrast agent into the blood), and a blood test.

In severe cases, the patient’s sputum, cerebrospinal fluid and serum are examined for the presence of herpes virus type 1 (HSV-1), mycoplasmas (single-cell bacteria) and respiratory viruses. The doctor pays attention to prolonged herpetic encephalitis, since there is a lot of evidence that it leads to encephalitis. Patients with this diagnosis cannot be treated with antiviral therapy; it is necessary to add immunomodulators (drugs that increase the body’s protective properties) to the course.

Features of differential diagnosis:

1. For diagnostic accuracy, patients who have been bitten by a mosquito or tick in the southern regions are carefully examined.
2. MRI is not the most sensitive diagnostic method. It allows one to detect pathological changes in the brain in only 1/3 of patients. When a contrast agent is introduced into the blood, only a slight increase in the signal from the cerebral cortex, brain stem, cerebellum and hippocampus can be detected. This increases the accuracy of the data obtained.
3. An electroencephalogram shows abnormal changes in brain function in 90% of cases. The method allows you to detect a general decrease in brain activity.

The doctor makes the final diagnosis when antibodies to NMDA receptors are found. In this case, the brain tissue, according to the results of the biopsy, turns out to be normal. In some patients (15%), antibodies can only be detected in the cerebrospinal fluid. Then an MRI or ultrasound of the pelvis, PET (positron emission tomography) or CT (computed tomography) of the whole body is performed.

Autoimmune diseases

There is also a group of encephalitis that are caused by autoimmune processes 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, and lead to disturbances in brain activity and the functioning of the peripheral nervous system. In addition to dementia, the disease is accompanied by paralysis and seizures similar to epileptic ones. 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 that is infectious or viral in nature. The rate of development of limbic encephalitis divides the disease into acute and subacute types. The causes of anti-receptor encephalitis will be discussed below.

Principles of treatment

When the patient’s relatives contact a medical facility, the latter is diagnosed with a primary psychiatric disorder (bipolar disorder or acute psychosis). In such cases, antipsychotics are given, which can complicate the situation and cause movement disorders - unnatural turns of the body, involuntary movements of the legs and arms.

Increased impulsiveness and frequent changes in emotional background are complemented by symptoms such as insomnia, hallucinations, and self-destructive behavior. A person does not control his actions, so he requires constant monitoring.

Patients are most often unable to swallow medications, so they are administered solutions intravenously or intramuscularly. Drugs can be delivered to the body through a nasogastric tube - inserted into the nose and secured. Medicines used:

• psychostimulants – eliminate impulsivity and hyperactivity;
• emotional swings are regulated by nomotymics and benzodiazepines;
• Haloperidol - eliminates symptoms of psychosis, is prescribed with caution - it can provoke increased movement disorders;
• Quentiapine – relieves anxiety and normalizes sleep.

In case of excessive speech and motor excitation, 2 mg of Lorazepam is administered intravenously at regular intervals. The daily dosage of the drug is 20-30 mg.

In severe cases, a person’s behavior changes to non-reactive – there is no speech, a feverish state occurs. Despite the immobility of the patient’s limbs, they can be easily bent and unbent, and strong tension is not felt in the muscles. At the same time, the person performs stereotypical movements. This complication is treated with electroconvulsive therapy (ECT).

ECT over 2-4 weeks (7-8 sessions) provides a reduction in the symptoms of anti-NMDA receptor encephalitis. The method is effective in many patients with impaired consciousness and various motor disorders.

Once a tumor is detected, the long-term prognosis improves. This is explained by the fact that the tumor can be removed surgically, as a result of which the source of antibodies will disappear. With early diagnosis and the use of aggressive therapeutic methods, a person's condition improves.

Since many patients are initially admitted to a psychiatric ward, it is important that the specialist does not exclude the possibility of developing psychosis as a consequence of anti-NMDA receptor encephalitis. This is especially true in cases where the patient has no past neuropsychiatric history.

Features of treatment:

1. If a tumor is found, it is excised and then first-line immunotherapy is given to speed up recovery. Plasmapheresis (collection, purification and return of blood), steroids, and immunoglobulin are prescribed. Within a month, more than half of patients feel improvement.
2. Second-line immunotherapy includes medications such as Rituximab and a monoclonal antibody, as well as the DNA cross-linker cyclophosphamide (used in the treatment of autoimmune diseases and cancer).
3. Treatment is supplemented with experimental drugs such as Alemtuzumab.

In 2021, German scientists from the Charité University Hospital made a discovery that makes it possible to more successfully treat encephalitis with antibodies to NMDA receptors. In the studies, in addition to standard therapy, patients were given a new substance, bortezomib, used for multiple myeloma. As a result of taking the new medicine, the condition of the experiment participants improved significantly. The experiment is carried out on seriously ill patients.

Treatment methods

The person is admitted to the intensive care unit, since the pathology often leads to respiratory problems. It is necessary to carry out artificial ventilation of the lungs.

After treatment for NMDA encephalitis, the disease does not return for 7 years.

The following manipulations are carried out as therapeutic methods:

• Plasmapheresis. Purification of human blood.
• Immunotherapy. Intravenous administration of immunoglobulin and glucocorticoids are required.
• Use of cytostatic agents.
• The use of anticonvulsant medications to eliminate seizures.
• The use of antipsychotics to control dyskinesias.

If a brain tumor is present, surgical intervention is required. Tumor inclusion affects the synthesis of antibodies that destroy nerve fibers. The faster the tumor is removed, the more likely recovery is.

Scientists continue to study the disease in order to invent effective treatment methods that can quickly cure the patient. To do this, it is necessary to investigate the molecular structures involved in the process of downregulation of NMDA receptors.

Among the new drugs that complement the main therapy, the substance bortezomide is highlighted, which effectively improves the patient’s condition in severe forms of the pathology. Protein begins to be actively produced, resulting in increased synthesis of antibodies. Bortezomide reduces the concentration of antibodies that influence the progression of encephalitis.

Consequences

The consequences of suffering from anti-NMDA receptor encephalitis are reflected in the state of the cognitive sphere. In some cases, during the rehabilitation period you will have to relearn how to walk and control your body. Sometimes patients involuntarily make movements with their hands.

Dangerous consequences include loss of sensitivity of certain receptors (hunger, thirst). The patient may not eat or drink for a long time, which increases the risk of worsening his condition. Loss of skin sensitivity can lead to burns and various injuries.

The patient's memory is deteriorating. Some people do not remember events that happened earlier than a week ago. During rehabilitation and after recovery, the patient has to take a large amount of medications.

Complications include progressive dementia (dementia). However, it does not develop in all cases.

About 50% of patients recover completely. A third of patients have minor residual effects. According to statistics, 10% of cases of the disease are fatal. When the tumor is at the initial stage of development, body functions are completely restored. The chance of a favorable outcome increases if you consult a doctor at the first symptom.

Example of a disease

Brief description of a clinical case from the abstract of an article in the journal Nature Clinical Practice Neurology, 2007:[13]

A 34-year-old woman consulted doctors about headache, fever and anxiety. These symptoms were soon followed by ideas of harm, aggressive agitation, seizures, hypoventilation, hyperthermia, and severe autonomic instability requiring intubation and sedation. Episodes of hypotension and bradycardia developed with asystolic periods of up to 15 seconds. When sedatives are withdrawn, the eyes open without reacting to external stimuli. Muscular rigor, frequent facial grimaces, rhythmic contractions of the abdominal muscles, kicking movements of the legs, and intermittent dystonic postures of the right hand were noted.

Culture and society

The symptoms of anti-NMDA receptor encephalitis have formed the basis of many works of fiction about the possession of demons in humans. Since the clinical manifestations of the disease are quite diverse, for a long time they could not distinguish it into a separate group of pathologies.

Renowned New York reporter Suzanne Cahalan has published a book, Brain on Fire: My Month of Madness. Subsequently, the work became a bestseller. The journalist talks about how long it took her illness to be identified, and how treatment and rehabilitation were carried out. The cost of medical procedures amounted to $1 million.

Lineman Amobi Okoye, a defensive end for the Dallas Cowboys, was treated for encephalitis for 17 months, including a three-month coma induced by doctors to keep his condition stable. After recovery, the football player returned to professional sports.

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Infectious and bacterial inflammations

The factors that cause infectious encephalitis are viruses and bacteria. For example, herpes virus, HIV infection, encephalitis virus, tuberculosis bacteria, streptococcus and staphylococcus, toxoplasma. In addition, tick-borne encephalitis is a serious problem. This is a viral disease spread by certain 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. Japanese encephalitis is also a viral species. The disease is very dangerous and in most cases 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 and has virtually no cure.

How does anti-receptor encephalitis manifest? Let's tell you in more detail.