Catatonic stupor

The totality of psychomotor symptoms, the main manifestations of which are immobility, rigidity of the skeletal muscles and refusal to speak, is called a catatonic stupor. Associated, as a rule, with schizophrenia,  [1] but can be observed in various diseases, not only directly related to the central nervous system, but also somatic: infectious, autoimmune, metabolic. The subphoric state is more common - impoverishment of motor skills, thinking and speech. Catatonic stupor is a severe and potentially life-threatening syndrome. [2]

Catatonic stupor can be accompanied by catalepsy, when the patient’s body can be placed in any position, often ridiculous and very uncomfortable, in which he freezes for a long time; negativity, when the patient’s posture cannot be changed because of his opposition. A catatonic stupor with numbness is also distinguished when the patient freezes in one kind of unnatural pose (very often assumes the position of an embryo) and stays in it, without moving or talking.

In the vast majority of cases, the stuporous state has a benign course and is quickly stopped by drugs of the benzodiazepine group.

Epidemiology

Catatonia is a complex clinical syndrome that occurs in more than 9-17% of patients with acute mental illness, and it is associated with many life-threatening complications. [3],  [4] In general, from 8 to 15% of all cases diagnosed as catatonia associated with epileptic condition. [5]

Causes

Catatonia, a particular case of which is stupor, is a manifestation of a psychotic disorder and is observed in a number of diseases, not only mental and neurological. Severe somatic diseases: typhoid fever, tuberculosis, syphilis, viral infections (AIDS, mononucleosis, flu), endocrinopathies, collagenoses, various metabolic and hormonal disorders affect the neurotransmitter metabolism in the cortex and subcortex of the brain, as a result of which the equilibrium state between the excitation functions is disturbed and braking in favor of the latter. A sub-stupor or stupor develops with limited or complete lack of motor activity, speech and hardening of skeletal muscles. [6], [7]

The pathological risk factors for the development of the catatonic syndrome are reduced by the American psychiatrists Fink and Taylor to a rather long list of diseases and conditions that can cause it. The catatonic spectrum of pathologies, first of all, included mental disorders, and, in the first place, not schizophrenia. To fall into a catatonic stupor, according to modern sources, people with depression, hysteria, or after consuming neurotoxic substances, including drugs, are much more likely than schizophrenics. Quite often, catatonic symptoms are observed in autists, it is not uncommon in children with developmental disorders and mental retardation. [8]

With temporal lobe epilepsy, an attack can occur in the form of a catatonic stupor. It is known that in some patients with non-convulsive status epilepticus catatonic stupor is observed. [9]

Many diseases in which a pathological condition develops suggest a hereditary predisposition (epilepsy, schizophrenia, autism spectrum disorders, etc.), many of which are acquired. Such stuporoznyh states may be consequences encephalitis  [10],  [11] tumors, hemorrhage, ischemic brain injury, subarachnoid hemorrhage and subdural hematoma,  [12] lupus or the antiphospholipid syndrome, secondary complications (liver disease or kidney disease)  [13] list is still possible to continue, it is quite extensive, but, in a small number of patients, the cause of the catatonic stupor is still not clear, it is treated as idiopathic.

Pathogenesis

The pathogenesis of this phenomenon is also hypothetical. All hypotheses are based on observation of patients, analysis of the effectiveness of therapy, for example, benzodiazepines or dopamine stimulants; situations associated with the development of catatonic stupor (abolition of clozapine, taking antipsychotics, antidepressants); the study of brain tomograms showing violations of neurobiological processes in the upper part of the thalamic zone of the diencephalon, frontal lobes of the cerebral cortex, small structures of the cerebellum, limbic system. However, the exact mechanism for the development of a catatonic stupor has not yet been described.

There is also a hypothesis that considers catatonic stupor as a reaction of the body to a near-death state. Indeed, it often develops in severely ill patients (lethal catatonia), however, a stuporous state is far from always assessed as hopeless.

Catatonia is most commonly associated with schizophrenia and other mental illnesses, such as severe depression, bipolar disorder, and psychosis. However, the causes of catatonia are numerous - from psychiatric to medical diseases. Therefore, it is not surprising that there are several suggested underlying mechanisms of catatonia, including downward modulation, cholinergic and serotonergic hyperactivity, sudden and massive dopamine blockade, and glutamate hyperactivity.

One theory suggests that catatonia involves “top-down modulation” in self-treatment of basal ganglia as a result of a deficiency of gamma-aminobutyric acid (GABA). [14] Downward modulation is described as a bidirectional process that determines our ability to focus on incentives that are appropriate to our needs and ignore reference information. Therefore, the successful interaction between amplification and suppression of neuronal activity creates the contrast necessary for the successful presentation of relevant information. Benzodiazepines bind to a specific GABA receptor site, making it more effective. As a result, an increase in chlorine ions occurs, which leads to an increase in the polarization of postsynaptic neurons, which makes them less excitable and more able to filter the corresponding stimuli. One report says that malignant catatonia can occur when benzodiazepine is withdrawn. [15] Another study suggests that glutamate hyperactivity may be different, underlying chemical dysfunction  [16], especially with a decrease in N - methyl d-aspartate receptor. [17]

Although the pathophysiology of catatonia is still unclear, several theories have been proposed based on available data. One possible interpretation of catatonia is that the syndrome is an external manifestation of severe anxiety. [18]

Studies of functional imaging have shown that catatonia is associated with altered activity in the orbitofrontal, prefrontal, parietal and motor regions of the cortex, suggesting that these cortical structures may also play a role in the pathophysiology of catatonia. This interpretation is supported by observations that GABA-A binding decreases in the cortical regions of patients with catatonia, motor and affective symptoms correlate with these disorders in GABA-A binding, and cortical disorders in patients with catatonia normalize after exposure to lorazepam. [19]

Whatever the pathophysiology of catatonia is, it is clear that a wide variety of underlying disorders can be associated with the appearance of catatonic signs. These include mood disorders, non-affective psychotic disorders, a number of medical and neurological conditions, and genetic disorders. [20] How - or if - these different etiologies converge on the last common pathway causing catatonia is unknown, and it is possible that the variations in the clinical picture of catatonia are different underlying mechanisms that will respond predominantly to different types of treatment. For example, future studies may allow doctors to identify patients who are unlikely to respond to lorazepam treatment and should receive ECT or other pharmacological treatment as a first-line option.

Symptoms

Catatonic stupor is associated with signs that reflect lack of movement, including immobility, gaze, mutism, rigidity, withdrawal and refusal to eat, as well as more bizarre features such as posture, grimace, negativism, waxy flexibility, echolalia or echopraxia, stereotypy, literature and automatic obedience. [21], [22]

The leading and most noticeable manifestation of stupor is immobility. The patient can suddenly freeze at any moment in the most unexpected and uncomfortable position and keep it for a long time - for weeks and months. His muscles are enslaved, which helps to maintain the position of the body. He falls silent and communication with him during this period is difficult, and often simply impossible. Stillness and mutism were again identified as the most common symptoms observed in 90.6% and 84.4%, respectively, of patients with catatonic disease.

Sometimes the increase in symptoms occurs in stages. Initially, a sub-stage develops, the first signs of which are manifested by inhibition in movements and speech. The range of movements decreases, and mobility itself is greatly reduced, speech is slow, meager, words are spoken with difficulty, sometimes it seems that the patient slowly thinks over each word. Inhibition can gradually increase until it ends in complete immobility. A characteristic feature of the sub-stupid state is that patients do not feel inconvenience from inhibition, do not make complaints if they see a doctor. This condition is perceived by them quite naturally and does not burden them, as in other cases when inhibition develops for other reasons, for example, as a side effect of psychotropic drugs.

The development of a sub-stupor does not mean at all that a true catatonic stupor will develop. In clinical practice, the so-called small catatonia is more common. Symptoms of a sub-stage are manifested in the poverty of facial expressions, speech, limitation and angularity of movements. The patient even communicates with the doctor only involuntarily, turns away when talking, trying not to look at his vis-a-vis, selects words with great difficulty, answering questions.

Symptoms of a catatonic stupor may vary. It is by the prevailing symptoms that the types of catatonic stupor are distinguished:

• cataleptic (with phenomena of wax flexibility) - when the patient’s posture can be changed to any, the most bizarre and uncomfortable, and this position of the body will be fixed for a long time; wax flexibility usually gradually masters all muscle groups: first of all, such muscle phenomena occur in the masticatory muscles, moving from top to bottom on the cervical muscles of the arms and legs; a characteristic pose for a cataleptic stupor - the patient’s head hangs in the air, as if leaning on an invisible pillow; [23]
• negativistic - the patient becomes numb in a certain position and resists any attempts to change it; passive negativism is distinguished, when the position of the body is maintained through strong muscle tension, and active, when the patient not only resists, but also tries to make a movement opposite to the imposed one;
• stupor with numbness - the patient freezes in the fetal position in the mother’s womb or in the air cushion with the most severe muscular tension (complete immobility and the absence of reactions to stimuli, including speech).

Cataleptic stupor can be replaced by a negative, and then complete numbness in an embryonic position. Any kind of stupor can be accompanied by a lack of speech, despite the fact that the patient does not lose his ability to express himself. Mutism can be complete, periodic, and selective, with options for breaking silence inexplicable.

In the structure of the catatonic stupor, a number of specific symptoms are observed, their difference is uncontrollability and aimlessness:

• automatic humility - the patient obeys absolutely any instructions from the outside (the opposite of negativity);
• stereotypies - a constant repetition of any actions (movements, sounds, words), not pursuing any visible goal, in particular, yaktion;
• echo symptoms - a constant repetition of someone their actions;
• Pavlov's symptom - with the onset of the dark, stuporous patients begin to talk, eat and move, in daylight - they again fall into a stupor;
• a symptom of a ladder - loss of smoothness of movement, for example, a cataleptic patient changes the position of a part of the body with outside help, but not smoothly, but in portions, jerkily;
• symptom of "proboscis", characteristic of a stupor with numbness - the patient's lips are elongated with a tube, resembling the proboscis of an elephant;
• Bernstein’s symptom - when one limb of a patient is raised, and then another, the first one is lowered;
• Bumke symptom - the absence of a pupil reaction to a pain stimulus;
• symptom of the hood - the patient is fenced off by all means at hand, for example, hanging with a towel, a bathrobe, pulling the hem of a shirt or blanket over his head.

Frequently encountered postures of stuporous patients also have their names - a Bedouin symptom, an “air cushion” symptom, and “crucifix” (an extreme manifestation of catalepsy).

Catatonic stupor with mutism also has features, for example, stubbornly silent patients give a reaction, answering questions if they are pressed on the eyes (Wagner-Yauregg symptom), or asked to another person (Saarma symptom). Sometimes they answer questions asked in a whisper. [24]

In a stuporous patient, some somatic symptoms and signs of an autonomic nervous system disorder are also observed. Blue lips and nails can be observed, hypersalivation and hyperhidrosis, a decrease in blood pressure, swelling, etc. Are observed.

Catatonic stupor can be of different depths and durations; sometimes it acquires a chronic course. Many are interested in the question: is a person conscious in a catatonic stupor?

On this basis, there is also a classification of catatonic syndrome .

Empty catatonia is characterized by the described symptom complex in various combinations without the addition of productive disorders (illusory visions, delusions and hallucinations). After exiting the attack, the patient can tell what was happening around, that is, his consciousness was not disturbed.

The presence of delusional hallucinatory symptoms does not mean that the patient's consciousness is necessarily impaired. Catatonic stupor, when the patient is conscious, that is, he correctly identifies himself and can subsequently correctly reproduce the events that have occurred, refers to lucid or pure catatonia. Without impaired consciousness, a catatonic stupor usually develops with schizophrenia (lucid catatonia).

Attacks with stupefaction include the oneiric-catatonic stupor with a visual-figurative delirium of the imagination. The patient in this case experiences a catatonic dream in which he is the main character. It is saturated with bright unreal events, with an intense emotional coloring, and the dream has a certain content. Coming out of the oneiric-catatonic state, the patient cannot remember what happened to him in reality, but he can describe the events that occurred in a dream very accurately. The oneiric-catatonic stupor continues for a long time - several days, and sometimes weeks. Onyroid develops with a stupor in epileptics, patients with injuries and tumors, after severe infections and poisonings, with paralytic dementia. More often in such patients, the basal nuclei of the brain are affected.

Lethal catatonic stupor develops in schizophrenics and people with impaired affect in the form of acute psychosis. Outwardly, the symptoms resemble oneiric stupor, but the development is rapid, and not only psychotic, but also somatic manifestations are growing. It is also called febrile, since one of the main symptoms is hyperthermia or jumping temperature (with normal catatonia, the patient's body temperature is normal). In addition to fever, the patient has a frequent pulse and rapid breathing, on the face - the so-called “Hippocrates mask” (earthy gray color, pointed features, sunken eyes, wandering eyes, dry lips, sweat droplets on the forehead, plaque on the tongue). The condition is reversible, but requiring urgent measures (in the first hours), otherwise it can take a malignant course. [25]

The catatonic syndrome in children is manifested mainly by the development of arousal, and then in rudimentary forms - uniform actions: bouncing, patting, pendulum-like walking from object to object, meaningless cries, pretentiousness, grimaces, etc. More often such excitement encompasses children in the late afternoon or when guests arrive. Unfolded adult cases of catatonic stupor are observed already in adolescence. Yet this is rare. Therefore, the catatonic stupor in childhood has not been studied and described enough, although in general, the symptomatology does not differ from this pathology in adults.

Complications and consequences

Catatonic stupor occurs in the severe course of many diseases and can end fatally,  [26]therefore, at the first signs of its development, you must consult a doctor. Patients in a catatonic stupor are usually hospitalized. They require intensive treatment and special care measures, because they often refuse to eat, do not follow basic sanitary and hygienic rules.

Forced feeding through a tube is fraught with disruptions in the gastrointestinal tract and the occurrence of metabolic problems. The consequence of prolonged lying or sitting in the same position can be pressure sores, hypostatic pneumonia, thrombosis; non-observance of personal hygiene rules leads to the development of infections in the oral cavity, genitourinary organs, dermatitis.

Catatonic stupor leads to the development of disorders of the skeletal muscles, for example, muscle contractures, paresis appear, the work of peripheral nerves is disrupted, various somatic health disorders develop.

On medical complications caused catatonia, reported in studies  [27],  [28]including rhabdomyolysis  [29],  [30] renal insufficiency  [31],  [32] decubitus,  [33] disseminated intravascular coagulation (DIC),  [34] tachycardia, bradycardia, cardiovascular collapse, acute respiratory distress syndrome, respiratory failure, myocardial myocardium, sepsis, convulsions, hypoglycemia, bleeding from the upper gastrointestinal tract, damage to the gastrointestinal tract, hepatocellular damage to the intestines, hepatocellular damage, tro deep vein mbosis and pulmonary thromboembolism. [35],  [36] However, despite the existence of these life-threatening conditions in some reports of cases of patients with catatonia, studies related to specific medical complications arising after catatonia, were not carried out, and as far as we know, a large-scale study to identify them and the largest study case series covered only 13 cases of catatonia. Moreover, the mechanisms underlying the development of these diseases in patients with catatonia remain to be seen.

Diagnostics

The condition of a stupor or sub-stage is diagnosed by clinical manifestations: the patient remains motionless in one position, lack of speech, the presence of other specific symptoms.

In addition to establishing the fact of the patient's stay in a catatonic stupor, the determination of the cause, that is, the disease that led to the development of this condition, becomes fundamental for determining treatment tactics. The patient's history is studied, close relatives are interviewed, the necessary tests and hardware studies are prescribed.

All patients with suspected catatonia should undergo EEG testing as a screening for other neurological conditions. EEG in catatonia is usually normal, unless there is a concomitant condition that may be the cause of the abnormality. [37],  [38] Given that catatonia can develop in the context of a wide range of neurological conditions, brain imaging is recommended, preferably with MRI. [39] In cases of catatonic stupor, immobility usually makes these studies easy to carry out. 

Laboratory tests should include a complete blood count, blood urea nitrogen, creatinine, muscle and liver enzymes, thyroid function tests, electrolytes, blood glucose, and urine tests to assess concomitant conditions, causes, or complications of catatonia. Marked dehydration is not uncommon in patients with catatonic disease, and attention should be paid to them. Vital signs should be evaluated frequently, since hypertension and fever (often accompanied by elevated levels of creatine phosphokinase, decreased serum iron and leukocytosis) can portend the occurrence of malignant catatonia or antipsychotic malignant syndrome if the patient received antipsychotic drugs. [40],  [41],  [42] If possible, there should be a thorough analysis of the last patient's medications and any changes. It is important to determine whether the patient received antipsychotic drugs or benzodiazepines, as we reported and continue to see, the development of catatonia after a sudden cessation of benzodiazepines. [43]

Unfortunately, the nature of catatonia makes some aspects of physical and neurological examination impossible. Components of a neurological examination that can usually be evaluated include pupil reaction, eye movements, corneal reflex, reaction to pain, salivation, instant response to a threat, reaction to light or sound, signs of frontal ejection, tone assessment, deep tendon reflexes and plantar response.

Differential diagnosis

Differential diagnosis should include diseases that mimic catatonia, such as Parkinson's akinetic disease, malignant hyperthermia, rigidity syndrome, conversion disorder, selective mutism (selective mutism is a social anxiety disorder in which people who can speak normally in some situations cannot speak in other situations - especially in performance scenarios), block syndrome and other hypokinetic and hyperkinetic conditions. [44]

Differential diagnosis is carried out with a convulsive epistatus (according to electroencephalography), with muscle stiffness syndrome, and other manifestations of hypokinetic syndromes in mental disorders.

The causes of catatonic stupor also differentiate among themselves. First of all, schizophrenia and affective disorders in the depressive phase are excluded. Magnetic resonance imaging allows you to exclude or confirm brain tumors and the consequences of its traumatic injuries, laboratory tests - intoxication, hormonal and metabolic disorders.

After a comprehensive examination, the patient is prescribed a course of treatment in accordance with the identified pathology. It happens that the cause of catatonia remains unknown (idiopathic catatonic stupor).

Treatment

Catatonic stupor responds well to low-dose benzodiazepines. [45] Lorazepam tablets have been found to be especially effective, according to researchers. A positive therapeutic response to lorazepam was demonstrated by 4/5 patients, and the symptoms disappeared completely and very quickly, two hours after administration. This tranquilizer, like other derivatives of benzidiazepine, enhances the action of γ-aminobutyric acid - the main neurotransmitter inhibition. With a low dosage, it has a sedative, anti-anxiety, some anticonvulsant and muscle-relaxing effect. It is effective not only with catatonic stupor, but also with excitement. Eliminates symptoms in schizophrenics, patients with depression and organic brain damage. But patients with addiction (drug, alcohol, medication) and with poisoning with these substances are not prescribed. 

The treatment of first-line catatonia is based on GABAergic drugs, especially benzodiazepines. The response rate to lorazepam is almost 80%. The efficacy of Olanzapine,  [46]  Risperidone and Modified Electroconvulsive Therapy (MECT) has been proven. [47] ECT should be considered in patients who do not respond to benzodiazepines a few days after the start of treatment. An exception to this strategy are patients with malignant catatonia, in which ECT should be prescribed at an early stage, since the disease has a high mortality rate. [48]

Although lorazepam and ECT have long been recognized as effective treatments for patients with catatonia, other options have been proposed. In a few cases, patients were described, effectively lechivshiesya zolpidem  [49],  [50] which is typical and benzodiazepines, can treat catatonia through interaction with the GABA A receptors. In addition, amantadine and memantine, which act as NMDA antagonists but also interact with a number of other neurotransmitter systems, have been shown to be effective in a small number of patients. [51],  [52] It is not clear whether these treatment options to be useful for a small proportion of patients who do not respond to lorazepam or to ECT.