Catatonic syndrome (psychiatry): treatment, symptoms

This concept in medical practice implies a set of symptoms manifested by psychomotor disorders. This pathology was first described in 1874 by Kahlbaum, who considered this disease as a separate nosological unit. Almost immediately it was recognized that catatonia is a symptom of schizophrenia. At the moment, experts do not adhere to such a clear position, highlighting several options for the causes of the pathology.

The disease can occur at any age. Including children. The peak of cases is in the age group of 17-30 years. The list of main symptoms includes:

• impulsive behavior;
• stupor;
• excitation.

Psychiatrists treat pathology. The combination of electroconvulsive and drug therapy makes it possible to successfully defeat the disease or transfer it to a stage of stable remission.

Catatonic syndrome: schizophrenia

The catatonic form is one of the manifestations of schizophrenia. It occurs in approximately 2.5% of all diagnosed cases of confirmation of this complex psychological illness. Many doctors believe that catatonic syndrome is unique to schizophrenia. In other situations, we can only talk about catatonic disorders.

The pathology is characterized by active and passive negativism, in which the patient resists when trying to change his posture. Patients suffering from active negativism refuse to carry out tasks received from the doctor. For example, when asked to sit down, the patient may defiantly remain standing and turn his back. In the passive form, the patient resists due to muscle tension.

Symptoms of catatonic syndrome

The presence of pathology can be determined by the symptoms of catatonic syndrome. It is necessary to contact for consultation at the first manifestations of the diagnosis. Timely initiation of treatment speeds up recovery.

The list of the most common symptoms includes:

• persistent repetition of facial expressions and movements surrounding stereotypy;
• counteracting attitude negativism;

• echo symptoms, in which the patient involuntarily repeats phrases and words;
• isolation;
• mutism, characterized by the patient’s inability to speak with full health of the speech apparatus;
• a strange body position with the head elevated, called “air cushion syndrome”;
• the grasping reflex, which manifests itself in the unreasonable grasping of surrounding objects;
• the presence of pathological flexibility;
• excessive facial expressions, grimaces;
• hypertrophied wide eyes.

The number of symptoms accompanying catatonic disorders is varied. Only a doctor can make an accurate determination. Some of them are particularly common. For example, the proboscis symptom noted in catatonic syndrome.

Proboscis symptom (In catatonic syndrome)

The position of the lips, in which, due to muscle contraction, they are constantly extended forward and form a “tube,” is a natural stage in the development of the facial muscles and facial expressions of a child in the first year of life. When pathology appears in an adult, it indicates the possible onset of catatonia.

Often proboscis syndrome is not accompanied by other manifestations of stupor or increased excitability. To eliminate the pathology, you need to contact a psychiatrist.

Carney complex is a rare hereditary neoplastic syndrome with an autosomal dominant inheritance pattern (OMIM 160980) [1], which is manifested by endocrine and non-endocrine neoplasia, many of which are specific to this syndrome. Timely diagnosis and treatment of Carney complex are extremely important for the prognosis of the patient’s life and genetic counseling for his family. Knowledge of the clinical symptoms and components of the Carney complex is of particular importance for endocrinologists, cardiologists, dermatologists, and urologists. Each of these specialists may encounter the first manifestations of the disease, and further observation and treatment depend on the correct direction of the diagnostic search.

History of discovery and terminology

The first description was made by a group of American scientists led by D. Carney [2] in 1985, who called this syndrome “a complex consisting of cardiac myxoma, pigmentation in the form of round spots and hyperactivity of the endocrine glands.” Previously, isolated cases [3, 4] of a combination of nevi, atrial myxoma and freckles—NAME syndrome or LAMB syndrome (lentiginosis, atrial myxoma and blue nevi)—were published. In 2000, it was possible to establish the genetic nature of this syndrome by identifying inactivating mutations in the protein kinase A regulatory 1α-subunit gene (PRKAR1A) in six families and in one sporadic case [5].

The same group of scientists described two more syndromes with similar names: the Carney triad (a combination of extra-adrenal paragangliomas, stromal tumors of the gastrointestinal tract and pulmonary chondroma with a high frequency of hormonally active and inactive adrenal adenomas) and Carney-Stratakis syndrome (a combination of paragangliomas with gastric sarcoma without pulmonary chondroma, OMIM 606864). The latter syndrome is associated with mutations in the succinate dehydrogenase genes (SHDB, SHDC, SHDD) [6, 7]. These hereditary syndromes are considered as separate nosological entities.

Epidemiology

According to a transatlantic consortium that collected data from several major centers (US National Institutes of Health, Mayo Clinic (USA), Cochin Hospital (France), until 2011, 353 patients from 185 families with Carney complex were described. Predominance of any ethnic groups not noted. In 32% of cases (113 patients), the disease was sporadic. Carney complex was diagnosed on average at 20 years of age; 5 patients were diagnosed at birth. Among postpubertal patients, women predominated (63%) [12].

In 2009, at the All-Russian Conference on Pediatric Endocrinology in St. Petersburg, for the first time in Russia, a case of Carney complex in a 14-year-old boy was reported; the diagnosis was confirmed genetically. Data on the number of cases of Carney complex in Russia, to our knowledge, have not yet been published. At the Institute of Pediatric Endocrinology of the Endocrinology Center, 3 patients under 16 years of age with Carney complex are currently under observation.

Clinical manifestations and diagnostic criteria

12 clinical signs that constitute the main diagnostic criteria have been identified. Two additional traits are based on pedigree analysis and genetic testing (Table 1).

The diagnosis can be established in the presence of two or more main clinical criteria or in the presence of one main and one additional (hereditary factor) [11].

Skin manifestations

Several skin symptoms are typical of Carney complex and are included in the main diagnostic criteria: lentiginosis, cutaneous and mucosal myxomas, blue epithelioid nevi (multiple) [11]. Skin pigmentation in the form of round spots (lentigines, blue nevi, café au lait spots, freckles) is the most common component of the Carney complex, which is observed in 70-80% of patients (see figure).

Figure 1. Lentiginosis in a 14-year-old patient with Carney complex (observation of the Institute of Pediatric Endocrinology, Endocrinology Center).

Lentiginosis consists of multiple brown or black spots of varying degrees of pigmentation, 4-10 mm in size. Typical localization of lentigo is the border of the lips, conjunctiva, outer and inner surfaces of the eyelids, and genital mucosa [13]. Lentiginosis is difficult to distinguish from ordinary freckles (or so-called “solar lentiginosis”). However, true lentiginosis does not change color intensity when exposed to sunlight, and is often located in areas of the body that are usually protected from sunlight. There are also histological differences: lentigo is represented by hyperplastic melanocytes, while freckles are characterized by a high pigment content in unchanged melanocytes [13]. Lentiginosis appears more often before the age of 20, is rarely found in prepubescent children, and is extremely rarely present at birth. After 40 years of age, pigmentation usually begins to fade (up to complete disappearance), but can also be noticeable in patients over 80 years of age [10]. Interestingly, in patients with Carney complex, despite an undoubted tendency to multiple neoplasias, no increased susceptibility to skin cancer was detected [14].

Careful examination of the patient's skin can play a key role in the diagnostic search, as clearly illustrated in some publications. Thus, A. Vandersteen [15] described a 15-year-old patient with cardiac myxoma, in whom, upon careful examination, lentigines around the lips and on the oral mucosa were discovered, which served as the basis for the diagnosis of Carney complex; Later, during a special examination, other symptoms of this syndrome were identified - testicular tumor and skin angiomyxoma.

Cutaneous myxomas (or otherwise - superficial angiomyxomas) can be located in all layers of the skin and can have a blue, pink, flesh-colored and even rainbow coloration. These are benign tumors that can recur, but never metastasize and, as a rule, do not cause concern to the patient. Myxomas can be found in any part of the body, but are most often located in the torso, neck, head and genitals. Their size varies from <2 to 7 cm or more. Multiple cutaneous myxomas almost certainly indicate Carney complex. The epithelioid component, present in 25% of lesions, is represented by basal proliferation and can be mistakenly regarded as basal cell carcinoma [16, 17].

Epithelioid blue nevi are characteristic skin lesions of Carney complex and are histologically indistinguishable from pigmented epithelioid melanocytoma, but are more often multiple and less likely to ulcerate [20, 21]. Their color varies from blue to white. One patient can simultaneously have up to 50 typical and atypical blue nevi [18]. Based on an examination of 16 patients, it was concluded that in patients with the most pronounced and varied skin manifestations, the number of endocrine neoplasia also increases [18].

Myxomas of the heart

Cardiac myxomas are benign endocardial tumors. They arise from pluripotent mesenchymal cells, which during embryogenesis can transform into endothelial cells, myoblasts, fibroblasts, angioblasts, and chondrocytes. Tumors are usually round or oval in shape with a lobulated surface of the peduncular and rarely sessile type, almost always localized in the atria, with 75% of sporadic cases in the left atrium. Clinical symptoms depend on the size and location of the myxoma; if they are small in size, there may be no symptoms. The most common clinical manifestations are vascular thromboembolism (cerebral, mesenteric, retinal arteries); Coronary thrombosis is also possible; cases of occlusion of the aortic trunk by a thrombus have been described [19]. About 10% of mixomas are a manifestation of the Carney complex. Cardiac myxomas are among the main clinical criteria of the disease and occur in 30-40% of cases of this syndrome. Unlike sporadic cardiac myxomas in hereditary syndrome, tumors are usually multifocal and can be located in any chamber of the heart. The average age of detection of cardiac myxomas is close to 50 years, but cases of their detection have also been described in young children (the earliest case is at 3 years); Late manifestation is also possible - after 60 years. Complications associated with cardiac myxomas - surgical (intra- and postoperative), thromboembolism and cardiac arrhythmias, according to 2001 data [11, 12], were the most common (more than 50%) causes of death in patients with Carney complex. Currently, apparently, due to advances in the treatment of myxomas of the heart, the cause of death is more often metastatic malignant neoplasms (schwannomas, carcinomas of the thyroid and pancreas, etc.).

Damage to the endocrine system

Primary pigmented nodular adrenal dysplasia (PPNAD)

- an extremely rare form of ACTH-independent hypercortisolism, in most cases associated with the Carney complex, but also occurs in another rare genetic disease - McCune-Albright-Braitsev syndrome. Among the endocrine manifestations of the Carney complex, PPNND is diagnosed in more than half of patients (60%) and may be the only clinical manifestation of this syndrome. In the largest study, 212 of 353 patients had PPNND, which was “isolated” in 12% of cases (n=44). The average age of diagnosis of PPNND was 34 years (19–60 years), while in women the disease manifested itself significantly earlier (on average at 30 years) than in men (on average at 46 years) [10]. Histologically, PPNND consists of black or brown nodules up to 1 cm in size (micronodular hyperplasia) against the background of an atrophied adrenal cortex. Symptoms of hypercortisolism can be expressed in varying degrees - from subclinical to the typical full clinical picture of Cushing's syndrome.

Many cases of PPNND have been described in which periods of exacerbation alternated with periods of spontaneous remission (“cyclic Cushing”). On the one hand, “cyclic Cushing” is not a constant characteristic of PPNND, and on the other hand, it also occurs with corticotropinomas [22]. A characteristic feature of PPNND is a paradoxical increase in cortisol levels in response to dexamethasone during the Liddle test. Liddle test is a modification of the dexamethasone test; it is carried out as follows: the level of cortisol in daily urine is assessed while taking dexamethasone at a dose of 2 mg/day for 2 days (small test), then 8 mg/day for the next 2 days (large test). An increase in the level of free cortisol in urine by 50% on the 4th day of the test (on the 2nd day of taking dexamethasone at a dose of 8 mg/day) is a diagnostic marker of PPNND [23]. A paradoxical cortisol response to the Liddle test was observed in 69% of patients with PPNND, but in rare cases such a response also occurs in patients with adrenal adenoma. The mechanism of hyperstimulation of the hyperplastic adrenal cortex by dexamethasone in PPNND is not completely clear. Dexamethasone has been shown to stimulate the catalytic subunit of protein kinase (PKA) via the glucocorticoid receptor, the expression of which is significantly higher in the affected adrenal gland than in the normal one [24].

Treatment of PPNND is reduced to bilateral adrenalectomy followed by replacement therapy. Unilateral adrenalectomy in some cases leads to temporary improvement, but in the future, most patients still develop hypercortisolism, requiring removal of the second adrenal gland. N. Sarlis et al. [25] described a patient with Carney complex and PPNND who, 27 years after unilateral adrenalectomy, showed signs of prolonged and severe hypercortisolism with severe osteoporosis, bone deformities, short stature, myopathy and moderate arterial hypertension. The basal level of cortisol was not increased, the ACTH content remained at the lower limit of normal, but there was no circadian rhythm, and the corticoliberin test was positive and a paradoxical cortisol response was noted with the Liddle test; a nodule was identified in the preserved adrenal gland. The authors believe that in many cases of the “positive” effect of unilateral adrenalectomy, there is persistence of hypercortisolism, gradually leading to clinical deterioration. Therefore, the only radical treatment for PPNND is bilateral adrenalectomy.

Massive formations of the adrenal glands (adenomas, carcinomas) are not typical for the Carney complex. Data on a patient with adrenal adenocarcinoma and lentiginosis and the results of an examination of 22 members of her family were recently published [26]. In 11 of them, including a patient with adrenal carcinoma, the S14G mutation was detected in the PPNAD gene, confirming the diagnosis of Carney complex. Clinical examination of mutation carriers revealed signs of PPNND in 3 of them, lentiginosis without signs of PPNND in 7, and in one carrier of the same mutation at the age of 53 years no signs of Carney complex were found at all. In this case, it is impossible to say with certainty that there is a direct relationship between adrenal cancer and a mutation in the PPNAD gene.

Large cell calcified Sertoli cell tumors (Sertoliomas)

- a rare variant of testicular tumors (less than 1% of all testicular tumors). They almost always serve as a manifestation of hereditary syndromes—Peutz-Jeghers syndrome or Carney complex [8, 10]. Among the endocrine components of the Carney complex, sertolioma ranks second in frequency and is detected in 40% of men. These tumors manifest at a young age (the average age of detection is 21 years). In most cases, tumors have multifocal lesions measuring 1-6 cm, often located bilaterally, which is especially typical for hereditary syndromes and less typical for sporadic cases. Clinically, tumors often manifest as gynecomastia due to high aromatase activity. Elevated levels of inhibin and testosterone can be detected as a manifestation of the hormonal activity of tumors, but this cannot be considered a diagnostic marker [27]. Also, tumors are benign in most cases. However, isolated cases of sertolioma malignancy with metastasis have been described, including those with Carney complex; malignant tumors are often solitary and large in size (more than 4 cm). They metastasize to regional retroperitoneal lymph nodes and rarely spread hematogenously to the liver and lungs [27, 29, 30]. Ultrasound reveals round hyperechoic formations (calcified) with clear contours, 5-10 mm in size, different from other calcifications (due to hematoma, granulomatosis, microlithiasis, etc.) [31]. Previously, in all cases, bilateral orchidectomy was recommended (for a bilateral process). Recently, more conservative tactics have increasingly been resorted to in cases of small (<2 cm) sizes, and in case of bilateral tumor localization, dynamic ultrasound control of its size, removal of a tumor larger than 2 cm while preserving the testicle, and orchidectomy are recommended in case of histological detection of signs of malignancy [ 32]. Recently, an aromatase inhibitor (anastrozole) was successfully used in prepubertal brothers with Peutz-Jeghers syndrome, which eliminated the symptoms of hyperestrogenism (gynecomastia and progression of bone age) [33].

In Carney complex, isolated cases of Leydigoma have been described, but they are not included in the main clinical criteria of this syndrome [5].

Ovarian cysts in patients with Carney complex are much less common than testicular tumors in men, but isolated cases of ovarian carcinoma have been described. Therefore, ultrasound of the pelvic organs is included in the diagnostic screening algorithm for possible components of the syndrome [31].

Somatotropinomas with symptoms of acromegaly were observed in 10-12% of patients, while in 75% of patients an asymptomatic increase in the level of growth hormone and IGF-1 was detected [35].

Very often, nodular and multinodular formations are also found in the thyroid gland (in 75%), but malignant tumors (follicular or papillary carcinomas) are rarely detected among them (2.5%) [12].

Psammotic melanotic schwannomas

Psammotic melanotic schwannomas are detected in 8-10% of patients with Carney complex. About 50% of all cases occur in the Carney complex. Most often, these tumors are localized in the dorsal ganglia or gastrointestinal tract. Unlike other types of schwannomas, they accumulate pigment, they contain psammotic bodies and often calcifications. It is these schwannomas that are the clinical criterion for Carney complex [12]. At the same time, a non-psammotic melanotic schwannoma of the trigeminal nerve was described in a patient with a typical Carney complex pattern and a mutation in the PRKAR1A gene (578-79delTG) [36]. The reason for the patient’s treatment was precisely the neurological symptoms associated with schwannoma, and other signs (lentiginosis, cardiac myxoma, multinodular goiter, ductal adenoma of the mammary gland) were discovered during further examination.

Osteochondromyxoma, a rare bone tumor, is one of the main clinical criteria for Carney complex. It can be either benign or malignant. D. Carney described 4 cases of osteochondromyxomas in children of the 1st year of life with a diagnosis of Carney complex. In 2 tumors were localized in the nasal bones and in the remaining 2 - in the fibula and tibia. In 1 case, the tumor had signs of malignancy [37].

Bilateral ductal adenoma of the mammary gland is also a diagnostic criterion for Carney complex.

Recently, it has been proposed to identify some more “suspicious” clinical symptoms that may be a reason for a diagnostic search for a possible association with the Carney complex, but they are not diagnostic criteria (Table 2) [12].

From our point of view, these additions create confusion in the practice of an endocrinologist and can lead to overdiagnosis and lead to unnecessary diagnostic examinations.

Genetic defects

At the end of the 90s of the 20th century, genetic linkage analysis made it possible to identify two loci (on the 2nd and 17th chromosomes) associated with the Carney complex [38]. In 2000, on chromosome 17, it was possible to identify a gene in which inactivating heterozygous mutations lead to the development of the Carney complex [39]. This gene encodes the protein kinase A regulatory α subunit (PRKAR1A); mutations in it have now been found in 73% of patients meeting the clinical criteria for Carney complex [10]. In the 10 years since the identification of the PRKAR1A gene, 117 different mutations have been described in patients. Mutations are distributed throughout the gene, but are detected with greater frequency in exons 2, 3, 5 and 8. The majority (70%) of the described mutations are point mutations (nucleotide deletions or insertions leading to a reading frame shift, nonsense mutations, splicing site defect, missense mutations). In most cases, these defects lead to premature formation of a stop codon [5, 10, 12, 16].

When examining 36 patients in whom direct sequencing did not detect mutations in the PRKAR1A gene, using the Southern blot method it was possible to identify two large deletions (a 4 kb deletion, including the 5th region, and a 4 kb deletion in the region of the 3rd exon) in 2 unrelated patients. On this basis, it is assumed that some patients with an unknown genotype actually have large deletions in the PRKAR1A gene [40]. It should be noted that the pseudogene PRKAR1A on chromosome 1 does not interfere with the study of PRKAR1A on chromosome 17, since it is not detected by standard sequencing methods [39].

In most cases, genetic defects are unique to each family; only three mutations have been described in more than three unrelated families of different ethnic groups: c.709-7del6 in the seventh intron was found in 14 families, c. 491-492delTG in the fifth exon - in 11 families, del578TG in exon 4B - in 6 families. The authors [5, 10, 39] conventionally call these mutations “frequent.”

Penetrance among carriers of PRKAR1A mutations is almost absolute and amounts to 88–97% [10, 39]. Mutations were found in 80% of patients with a “complicated” pedigree and in 37% of “sporadic” cases [10]. However, families with low penetrance have been described. M. Gennari et al. [41] described an Italian family where the proband fully met the clinical criteria of Carney complex and also had hepatocellular carcinoma, and in 10 relatives - carriers of the same inactivating mutation PRKAR1A c.502+1G>A - significant variability in the phenotype was observed. L. Groussin et al. [42] examined 12 families with the same PRKAR1A c.709-7del6 mutation and isolated PPNND in 7 healthy carrier relatives and did not reveal any clinical signs of the disease at all. Only one woman had a history of papillary thyroid carcinoma. The authors conclude that the PRKAR1A mutation c. 709-7del6 has low penetrance and results in isolated PPNND.

The gene on chromosome 2 has not yet been identified. Perhaps it is responsible for the development of the disease in some patients who do not have mutations in the PRKAR1A gene.

Correlation of genotype and phenotype

Since most mutations in the PRKAR1A gene are unique and are not repeated in other families, it is not possible to trace strict relationships between them and the characteristics of clinical manifestations. However, in rare cases, some genotypic correlations have been observed. L. Groussin et al. [43] analyzed 12 families in which the same PRKAR1A mutation was detected [6-nucleotide deletion in intron 6 (c.709-7del6)]. All patients had isolated PPNND, and a special examination did not reveal other manifestations of the Carney complex. Recently, an association of isolated PPNND with the M1V missense mutation in the PRKAR1A gene in two families was also described [47]. J. Bertherat et al. [10] analyzed 80 different genotypes in 353 patients with Carney complex and also identified some trends: acromegaly, cardiac myxomas, lentiginosis and schwannomas were more often observed in carriers of exonic mutations compared to intronic ones (p = 0.04); "common" mutation c. 491-492delTG was more often associated with cardiac myxomas, lentiginosis, and thyroid tumors than others (p=0.03).

Genotype-phenotype correlations provide additional opportunities for genetic counseling and determining patient monitoring tactics.

Other genetic factors influencing phenotype

In recent years, much attention has been paid to factors that may influence phenotypic variability in monogenic diseases. A major role in this is played by modifying genes, which have an effect similar to predisposing genes in polygenic diseases. Recently [43], the phosphodiesterase 11A (PDE11A) gene was shown to be a modifying gene influencing the phenotype of patients with the PRKAR1A mutation. Among patients with germline PRKAR1A mutation, PDE11A gene mutations were detected significantly more often (25.3%) than in the control group (6.8%, p<0.001). In addition, among patients with PPNND and Sertoli cell calcified tumors, PDE11A defects were observed more often than in patients without these manifestations. This association was stronger among men with PPNDD (80%) than among women (20%), although PPNDD is more common among women with Carney complex. The authors do not provide a detailed explanation for this. PDE11A is highly expressed in adrenal and gonadal steroid cells. A predisposing effect of this gene on the development of sporadic tumors of the adrenal glands and testicles was discovered [44]. In addition, mutations in the PDE11A gene were found in 5 patients with isolated micronodular adrenal dysplasia (iMNAD), who did not have mutations in the PRKAR1A gene. In contrast to PPNND in Carney complex, in patients with iMND and PDE11A mutations, the adrenal glands, against the background of a normal non-atrophied cortex, contained yellow-brown micronodules that did not contain pigment. However, in some cases, the histological picture did not differ from that of PPNND [46].

Interestingly, a number of publications [45] are devoted to the role of the PDE11A gene in the formation of mental disorders and the association of its variants with different sensitivity to psychotropic drugs.

The role of the regulatory α-subunit of protein kinase A type 1 (R1α) in the pathogenesis of the Carney complex

The regulatory α-subunit of protein kinase A type 1, encoded by the PRKAR1A gene, is a major component of this enzyme. cAMP-dependent protein kinase A (PKA) consists of four subunits—two catalytic (C) and two regulatory (R). When bound to cAMP, regulatory subunits dissociate, and catalytic subunits phosphorylate serine and threonine residues of more than 100 different proteins [48]. The mechanisms of RCA functioning are still not fully understood. PKA is involved in the process of gene transcription, signal transduction mechanisms, cell proliferation, cell differentiation and apoptosis. Two isomers of PKA are known (types 1 and 2), as well as 4 isoforms of the regulatory subunit (R1α, R1β, R2α, R2β) and 3 isoforms of the catalytic subunit (Cα, Cβ, Cγ). Each isoform is encoded by its own gene. PKA type 1 is considered the main mediator of the cAMP signaling system in human cells. Most mutations in the PRKAR1A gene in patients with Carney complex lead to premature formation of a stop codon and, accordingly, a decrease in the level of R1α by 50% or more. In the lymphocytes of patients with mutations leading to the formation of a stop codon, the truncated PRKAR1A protein, which should be formed as a result of such a gene defect, was not detected. This turned out to be associated with the mechanism of the so-called nonsense-mediated degradation of mRNA, in which the destruction of mRNA occurs even before translation. Thus, a truncated “defective” protein is not formed, and in a cell with a heterozygous mutation, only a low (less than 50%) level of normal protein is detected [39]. R1α deficiency leads to increased PKA activity, which is observed in tumor cells from patients with Carney complex [49]. In some tumors (retinoblastomas, breast and kidney carcinomas, malignant osteoblastomas, etc.), on the contrary, increased expression of R1α was found. This may be explained, in particular, by the fact that the effects of PKA depend on many factors - the specific tissue, the stage of cell differentiation, the level of cAMP, and the duration of protein kinase activation. In addition, there is evidence of an independent role of R1α, independent of PKA [50].

The PRKAR1A gene does not fully meet the criteria for a tumor suppression gene or the definition of an oncogene. The role of R1α PKA type 1 in the development of the clinical components of the Carney complex is obvious, but the molecular mechanisms of the pathogenesis of this syndrome remain incompletely understood.

Conclusion

Carney complex is a rare hereditary syndrome with an autosomal dominant inheritance pattern that can be classified as a group of multiple endocrine neoplasias. The genetic nature is only partially established; only 73% of patients are carriers of a mutation in the PRKAR1A gene, and some are found to have linkage to a locus on chromosome 2, in which the gene has not yet been identified, which indicates the genetic heterogeneity of this syndrome. However, genetic diagnosis is possible in the majority of patients, which should be used when counseling families. Lentiginosis is one of the most common manifestations of the Carney complex. With Carney complex, there are rare variants of endocrine neoplasia - PPNND, large cell calcified sertolioma, as well as other rare neoplasias (cardiac myxoma, cutaneous neoplasia, schwannomas). The discovery of one of the main components of the Carney complex should lead to a search for other components of the syndrome. All patients with Carney complex should be under the supervision of specialists. Further studies of the functions of PKA and its regulatory α-subunit, which determine the clinical heterogeneity of the disease, are needed.

Treatment of catatonic syndrome

Treatment of this pathology can only be carried out in a specialized psychiatric hospital. After a thorough examination, an individual course of therapy is developed for each patient. Medications play a major role in this:

• mood stabilizers;
• benzodiazepines;
• antiglutamantics;
• muscle relaxants;
• neuroleptics.

Additionally, electroconvulsive therapy is prescribed. In the case of malignant forms of pathology, such therapy is prescribed primarily to relieve the acute stage. The therapy involves passing electrical impulses through the brain tissue. The procedure is performed only in a hospital under the supervision of a doctor. If necessary, call an ambulance. After completion of the course, drug therapy continues.

Existing treatments

Unfortunately, it is very rare to completely get rid of Cotard's syndrome. This is due to patients seeking medical help late. In order to correct disorders of brain function, medications of various groups are used:

1. The basis of treatment is antipsychotic drugs such as Aminazin and Rispolept. They help fight anxiety, reduce the risk of injury, and also help normalize the functioning of the nervous system.
2. Antidepressants are widely used in the treatment of walking dead syndrome. Drugs such as Amitriptyline are used.
3. Anxiolytics are indicated for severe anxiety in the patient. This group of medications includes Grandaxin. These drugs are successfully combined with antidepressants.
4. In severe cases, the use of tranquilizers is indicated. They are used when there is a high risk of injury and suicide. Drugs such as Phenazepam are prescribed.

In some cases, in addition to medications, electroconvulsive therapy is used. Some doctors and medical institutions refuse this method because they consider it outdated and cruel. However, despite this, with the help of this technique it is possible to achieve visible results. This is possible due to the effect of low current on the brain, which leads to a change in the pathological functioning of neurons. A combination of this technique with drug treatment is also indicated.

Communication with a psychiatrist is also important. Such sessions are conducted both individually and in small groups. Through a conversation with the patient, it is possible to enhance the therapeutic effect of the pharmacological drugs taken, as well as evaluate the effectiveness of treatment.

In many cases, the diagnosis of Cotard's syndrome requires hospitalization of the patient in specialized institutions. This is associated with a high risk of suicide and trauma, as well as the need for constant monitoring. Once the person’s condition has stabilized, therapy can be carried out on an outpatient basis. Even in the absence of clinical manifestations of the disorder, patients are registered at a psychiatric clinic. This is important for controlling the disease and preventing relapses.

Types of catatonic syndrome

Manifestations of pathology differ depending on the type. Only a doctor can make an accurate diagnosis.

Affective syndromes

They are accompanied by frequent changes in behavior from a high level of disinhibition to states of catatonic sleep and complete refusal to interact with the outside world.

Delusional syndromes

Obsessive movements are accompanied by delirium. Delusional states can also occur with passive negativism. This further aggravates the patient’s retreat into his inner world and refusal to communicate.

Hallucinatory syndromes

Patients in both the active and passive stages may experience hallucinations. In a state of stupor and lack of reaction to the outside world, this further worsens the patient’s condition. With active negativity of the patient, they can become socially dangerous.

Oneiric catatonic syndrome

It begins immediately with the acute phase, characterized by a noticeable increase in psychomotor agitation. In this state, the patient can be dangerous to others, and manic thoughts may arise. Moreover, in this state the patient seems to be in a waking dream. In perception, real and fictitious circumstances alternate.

Regressive catatonic syndrome

This variant of pathology turns an adult into a child in terms of behavioral style. Moreover, often in an infant. The sounds produced may resemble meowing.

Lucid catatonic syndrome

Characterized by the absence of delirium, stupor, or hallucinations. An increased level of excitement manifests itself, movements become abrupt and fussy. Stupor with numbness and negativistic stupor will occur.

Clinical picture

Periodic fever is a hallmark of Marshall syndrome. It begins suddenly and is often accompanied by chills. The temperature ranges from 38.5 to 41 ºC for 2-7 days, and then drops sharply to normal. Before the fever, the child may experience irritability, mood swings, complain of malaise, sore throat, and aphthous ulcers appear in the mouth.

Aphthous stomatitis - ulcers usually located on the inside of the lips or buccal mucosa, occur in approximately 40-80% of patients.

Pharyngitis (sometimes with exudate - liquid contents in the tonsils, less often with ulcers on the tonsils) occurs in 65-100% of patients.

Cervical lymphadenopathy (enlarged lymph nodes) accompanies fever in 60–100% of patients. Cervical lymph nodes may be painful to palpation.

Other symptoms: abdominal pain (40-65%), joint pain (11-42%), vomiting (18-41%) and headache (18-65%). Less common are diarrhea, cough, runny nose and rash.

In adulthood, episodes rarely have a uniform interval between attacks, and the attack itself is rarely diagnosed as pharyngitis, with chest pain, headache, arthralgia (joint pain), myalgia (muscle pain), eye symptoms and rash more common.