Catatonic stupor

A set of psychomotor symptoms, the main manifestations of which are immobility, rigidity of skeletal muscles and refusal to speak, is called catatonic stupor. It is usually associated 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. More common is a substuporous state - impoverishment of motor skills, thinking and speech. Catatonic stupor is a severe and potentially life-threatening syndrome. [ 2 ]

Catatonic stupor may be accompanied by catalepsy, when the patient's body can be put into any position, often absurd and very uncomfortable, in which he freezes for a long time; negativism, when the patient's position cannot be changed due to his resistance. Catatonic stupor with numbness is also distinguished, when the patient freezes in one unnatural position (very often takes the position of an embryo) and remains in it, without moving or speaking.

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

Epidemiology

Catatonia is a complex clinical syndrome occurring in more than 9-17% of patients with acute mental illness and is associated with a variety of life-threatening complications.[ 3 ],[ 4 ] Overall, 8 to 15% of all cases diagnosed as catatonia are associated with an epileptic condition.[ 5 ]

Causes catatonic stupor

Catatonia, a special 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 between the functions of excitation and inhibition is disturbed in favor of the latter. Substupor or stupor with limited or complete absence of motor activity, speech and hardening of skeletal muscles develops. [ 6 ], [ 7 ]

Pathological risk factors for the development of catatonic syndrome are summarized by American psychiatrists Fink and Taylor in a fairly long list of diseases and conditions that can cause it. The catatonic spectrum of pathologies primarily includes mental disorders, and schizophrenia is by no means in first place. According to modern sources, people suffering from depression, hysteria, or after taking neurotoxic substances, including medications, are much more likely to fall into catatonic stupor than schizophrenics. Catatonic symptoms are quite often observed in autistics, and they are also not uncommon in children with developmental disabilities and mental retardation. [ 8 ]

In temporal lobe epilepsy, the seizure may occur as a catatonic stupor. It is known that some patients with non-convulsive status epilepticus experience catatonic stupor. [ 9 ]

Many diseases that cause pathological conditions involve a hereditary predisposition (epilepsy, schizophrenia, autism spectrum disorders, etc.), many are acquired. Such stuporous states can be consequences of encephalitis, [ 10 ], [ 11 ] tumors, hemorrhages, ischemia, brain injury, subarachnoid hemorrhage and subdural hematoma, [ 12 ] systemic lupus erythematosus or antiphospholipid syndrome, secondary complications (liver or kidney disease) [ 13 ] The list can be continued, it is quite extensive, however, in a small number of patients the cause of catatonic stupor cannot be determined, it is interpreted 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 (clozapine withdrawal, taking neuroleptics, antidepressants); study of brain tomograms showing disturbances in neurobiological processes in the upper part of the thalamic zone of the diencephalon, frontal lobes of the cerebral cortex, small structures of the cerebellum, and limbic system. However, the exact mechanism of development of catatonic stupor has not yet been described.

There is also a hypothesis that considers catatonic stupor as the body's reaction to a pre-death state. Indeed, it often develops in seriously ill patients (lethal catatonia), however, the stuporous state is not always assessed as hopeless.

Catatonia is most commonly associated with schizophrenia and other mental illnesses such as major depression, bipolar disorder, and psychosis. However, the causes of catatonia are numerous, ranging from psychiatric to medical illnesses. It is therefore not surprising that there are several proposed underlying mechanisms of catatonia, including descending modulation, cholinergic and serotonergic hyperactivity, sudden and massive dopamine blockade, and glutamate hyperactivity.

One theory suggests that catatonia involves "top-down modulation" of basal ganglia self-processing as a result of gamma-aminobutyric acid (GABA) deficiency.[ 14 ] Top-down modulation is described as a bidirectional process that determines our ability to focus on stimuli relevant to our needs and ignore background information. Therefore, successful interaction between enhancing and suppressing neuronal activity creates the contrast needed to successfully present relevant information. Benzodiazepines bind to a specific site on the GABA receptor, making it more effective. This results in an increase in chloride ions, which leads to increased polarization of postsynaptic neurons, making them less excitable and more able to filter out relevant stimuli. One report suggests that malignant catatonia may occur with benzodiazepine withdrawal. [ 15 ] Other research suggests that glutamate hyperactivity may be another underlying chemical dysfunction, [ 16 ], particularly with decreased N-methyl d-aspartate receptor activity. [ 17 ]

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

Functional imaging studies have shown that catatonia is associated with altered activity in the orbitofrontal, prefrontal, parietal, and motor cortex, suggesting that these cortical structures may also play a role in the pathophysiology of catatonia. This interpretation is supported by the observations that GABA-A binding is reduced in cortical areas of patients with catatonia, motor and affective symptoms correlate with these abnormalities in GABA-A binding, and that cortical abnormalities in patients with catatonia are normalized following lorazepam treatment.[ 19 ]

Whatever the pathophysiology of catatonia, it is clear that a wide variety of underlying disorders may be associated with the occurrence of catatonic features. 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 a final common pathway causing catatonia is unknown, and it is possible that variations in the clinical presentation of catatonia represent different underlying mechanisms that will respond preferentially to different treatments. For example, future research may allow clinicians 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

Catatonic stupor is associated with signs reflecting a lack of movement, including immobility, staring, mutism, rigidity, withdrawal, and refusal to eat, as well as more bizarre features such as posturing, grimacing, negativism, waxy flexibility, echolalia or echopraxia, stereotypy, verbalism, and automatic obedience.[ 21 ],[ 22 ]

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

Sometimes the symptoms increase in stages. At first, a substupor develops, the first signs of which are manifested by inhibition of movements and speech. The range of movements decreases, and mobility itself is greatly reduced, speech is slow, sparse, words are pronounced with difficulty, sometimes it seems that the patient is slowly thinking over each word. Inhibition can increase gradually until it ends in complete immobility. A characteristic feature of the substuporous state is that patients do not feel discomfort from inhibition, do not make complaints if they get to the doctor. This condition is perceived by them as completely natural 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 substupor does not mean that true catatonic stupor will develop. In clinical practice, the so-called minor catatonia is more common. Symptoms of substupor are manifested in the poverty of facial expressions, speech, limited and angular movements. The patient communicates even with the doctor only under duress, turns away during conversation, trying not to look at his vis-à-vis, and has great difficulty choosing words when answering questions.

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

• cataleptic (with phenomena of waxy flexibility) - when the patient's position can be changed to any, the most bizarre and uncomfortable, and this body position is fixed for a long time; waxy flexibility usually gradually takes over all muscle groups: first of all, such muscle phenomena occur in the chewing muscles, moving from top to bottom to the neck, muscles of the arms and legs; a characteristic pose for cataleptic stupor is the patient's head hanging in the air, as if resting on an invisible pillow; [ 23 ]
• negativistic - the patient freezes in a certain position and resists any attempts to change it; a distinction is made between passive negativism, when the body position 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 an air cushion with severe muscle tension (complete immobility and lack of reaction to stimuli, including speech).

Cataleptic stupor may be replaced by negativistic, and then complete numbness in the embryonic position. Any type of stupor may be accompanied by the absence of speech, although the patient does not lose the ability to express himself. Mutism may be complete, periodic and selective, and the options for interrupting the silence are inexplicable.

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

• automatic obedience - the patient obeys absolutely any instructions from the outside (the opposite of negativism);
• Stereotypes - constant repetition of any actions (movements, sounds, words) that do not pursue any visible goal, in particular, jactation;
• echo symptoms - constant repetition of someone else's actions;
• Pavlov's symptom - with the onset of darkness, stuporous patients begin to talk, eat and move, in daylight hours they again fall into a stupor;
• staircase symptom - loss of smoothness of movement, for example, a cataleptic patient changes the position of a body part with outside help, but not smoothly, but in portions, in jerks;
• the "trunk" symptom, characteristic of stupor with numbness - the patient's lips are stretched out like a tube, resembling an elephant's trunk;
• Bernstein's symptom - when one limb of the patient is raised and then the other, the first one drops;
• Bumke's symptom - absence of pupillary response to pain stimulus;
• hood symptom - the patient isolates himself from everyone using improvised means, for example, by covering himself with a towel, a robe, or pulling the hem of a shirt or blanket over his head.

Frequently encountered postures of stuporous patients also have their own names - the Bedouin symptom, the "air cushion" symptom, "crucifixion" (an extreme manifestation of catalepsy).

Catatonic stupor with mutism also has its own characteristics, for example, stubbornly silent patients react by answering questions if their eyes are pressed (Wagner-Jauregg symptom) or asked to another person (Saarma symptom). Sometimes they answer questions asked in a whisper. [ 24 ]

A patient with stupor also exhibits some somatic symptoms and signs of autonomic nervous system disorder. The lips and nails may turn blue, hypersalivation and hyperhidrosis may be observed, blood pressure may drop, edema may occur, etc.

Catatonic stupor can be of varying depth and duration, sometimes it becomes chronic. Many people are interested in the question: is a person in a catatonic stupor conscious?

There is also a classification of catatonic syndrome based on this feature.

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

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

Oneiroid-catatonic stupor with visual-figurative delusions of the imagination is an attack with clouded consciousness. In this case, the patient experiences a catatonic dream in which he is the main character. It is filled with vivid unreal events, with intense emotional coloring, and the dream has a certain content. After emerging from the oneiroid-catatonic state, the patient cannot remember what happened to him in reality, but he can describe the events that occurred in the dream quite accurately. Oneiroid-catatonic stupor lasts for quite a long time - several days, and sometimes weeks. Oneiroid develops during stupor in epileptics, patients with injuries and tumors, after severe infections and poisoning, with paralytic dementia. Most often, the basal nuclei of the brain are affected in such patients.

Lethal catatonic stupor develops in schizophrenics and individuals with affective disorders in the form of acute psychosis. Outwardly, the symptoms resemble oneiroid stupor, but the development is rapid, and not only psychotic, but also somatic manifestations increase. It is also called febrile, since one of the main symptoms is hyperthermia or fluctuating temperature (with normal catatonia, the patient's body temperature is normal). In addition to fever, the patient has a rapid pulse and rapid breathing, and the so-called "Hippocratic mask" on the face (earthy-gray color, pointed features, sunken eye sockets, wandering gaze, dry lips, beads of sweat on the forehead, plaque on the tongue). The condition is reversible, but requires urgent measures (in the first hours), otherwise it can take a malignant course. [ 25 ]

Catatonic syndrome in children manifests itself mainly by the development of excitement, and then in rudimentary forms - monotonous actions: jumping, patting, pendulum-like walking from object to object, meaningless cries, pretentiousness, grimaces, etc. More often, such excitement takes hold of children closer to evening or when guests appear. Cases of catatonic stupor developed in an adult manner are observed already in adolescence. However, this is rarely observed. Therefore, catatonic stupor in childhood has not been sufficiently studied and described, although in general, the symptoms do not differ from this pathology in adults.

Complications and consequences

Catatonic stupor occurs in severe cases of many diseases and can be fatal, [ 26 ] therefore, at the first signs of its development, it is necessary to consult a doctor. Patients in catatonic stupor are usually hospitalized. They require intensive treatment and special care measures, since they often refuse to eat and do not follow basic sanitary and hygienic rules.

Forced tube feeding is fraught with gastrointestinal tract disorders and metabolic problems. Bedsores, hypostatic pneumonia, thrombosis may result from prolonged lying or sitting in one position; failure to observe personal hygiene rules leads to the development of infections in the oral cavity, genitourinary organs, and dermatitis.

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

Medical complications due to catatonia have been reported in studies,[ 27 ],[ 28 ] including rhabdomyolysis,[ 29 ],[ 30 ] renal failure,[ 31 ],[ 32 ] pressure ulcers,[ 33 ] disseminated intravascular coagulation (DIC),[ 34 ] tachycardia, bradycardia, cardiovascular collapse, acute respiratory distress syndrome, respiratory arrest, myocardial infarction, sepsis, seizures, hypoglycemia, upper gastrointestinal bleeding, gastrointestinal injury, hepatocellular injury, hepatocellular damage, deep vein thrombosis, and pulmonary embolism. [ 35 ], [ 36 ] However, despite the presence of these life-threatening conditions in some case reports of patients with catatonia, studies regarding specific medical complications arising after catatonia have not been conducted and, to the best of our knowledge, no large-scale study to identify them and the largest case series study included only 13 cases of catatonia. Moreover, the mechanisms underlying the development of these diseases in patients with catatonia remain to be elucidated.

Diagnostics catatonic stupor

The state of stupor or substupor is diagnosed by clinical manifestations: the patient remains motionless in one position, lack of speech, and the presence of other specific symptoms.

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

All patients suspected of having catatonia should undergo EEG testing as a screening for other neurological conditions. The EEG in catatonia is usually normal unless there is an underlying condition that could be causing the abnormality.[ 37 ],[ 38 ] Given that catatonia can occur in the context of a wide range of neurological conditions, brain imaging, preferably with MRI, is recommended.[ 39 ] In cases of catatonic stupor, immobility usually allows these studies to be performed easily.

Laboratory studies should include a complete blood count, blood urea nitrogen, creatinine, muscle and liver enzymes, thyroid function tests, electrolytes, blood glucose, and urinalysis to evaluate for coexisting conditions and causes or complications of catatonia. Marked dehydration is not uncommon in patients with catatonia and should be addressed. Vital signs should be assessed frequently, as hypertension and fever (often accompanied by elevated creatine phosphokinase, decreased serum iron, and leukocytosis) may herald the onset of malignant catatonia or neuroleptic malignant syndrome if the patient has been receiving antipsychotics.[ 40 ],[ 41 ],[ 42 ] Whenever possible, a thorough review of the patient's recent medications and any changes should be obtained. It is important to determine whether the patient was receiving antipsychotics or benzodiazepines, as we have reported and continue to see the development of catatonia after abrupt discontinuation of benzodiazepines.[ 43 ]

Unfortunately, the nature of catatonia makes some aspects of the physical and neurologic examination impossible. Components of the neurologic examination that can usually be assessed include pupillary response, eye movements, corneal reflex, response to pain, presence of salivation, immediate threat response, response to light or sound, frontal ejection signs, tone assessment, deep tendon reflexes, and plantar response.

Differential diagnosis

The differential diagnosis should include disorders that mimic catatonia, such as akinetic Parkinson's 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 are unable to speak in other situations - especially in performance scenarios), lock-in syndrome, and other hypokinetic and hyperkinetic states.[ 44 ]

Differential diagnosis is carried out with non-convulsive status epilepticus (according to electroencephalography data), with muscle stiffness syndrome, and other manifestations of hypokinetic syndromes in mental disorders.

The causes of catatonic stupor are also differentiated. First of all, schizophrenia and affective disorders in the depressive phase are excluded. Magnetic resonance imaging allows excluding or confirming brain tumors and the consequences of its traumatic injuries, laboratory studies - 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

Catatonic stupor responds well to treatment with benzodiazepines in low doses. [ 45 ] According to researchers, lorazepam tablets have proven to be particularly effective. 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 benzodiazepine derivatives, enhances the effect of γ-aminobutyric acid, the main inhibitory neurotransmitter. When taken in low doses, it has a sedative, anti-anxiety, some anticonvulsant and muscle-relaxing effect. It is effective not only in catatonic stupor, but also in agitation. It eliminates symptoms in schizophrenics, patients with depression and organic brain damage. However, it is not prescribed to patients with addiction (drug, alcohol, medication) and in cases of poisoning with these substances.

First-line treatment of catatonia is based on GABAergic drugs, especially benzodiazepines. The response rate to lorazepam is almost 80%. Olanzapine, [ 46 ] Risperidone and modified electroconvulsive therapy (MECT) have been shown to be effective. [ 47 ] ECT should be considered in patients who do not respond to benzodiazepines after a few days of treatment. An exception to this strategy is patients with malignant catatonia, in which ECT should be administered early because 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. Several case reports have described patients being effectively treated with zolpidem,[ 49 ],[ 50 ] which, like typical benzodiazepines, can treat catatonia by interacting with GABA-A receptors. Additionally, amantadine and memantine, which act as NMDA antagonists but also interact with a number of other neurotransmitter systems, have shown efficacy in a small number of patients.[ 51 ],[ 52 ] It is unclear whether these treatment options may be useful for the small proportion of patients who do not respond to either lorazepam or ECT.