What is Neurosyphilis?
Neurosyphilis develops as a result of penetration into the central nervous system of the causative agent of the disease – pale treponema.
A few decades ago, syphilitic damage to the central nervous system was quite common. Currently, as a result of the development of effective methods for treating syphilis and a sharp decrease in the incidence, as well as because of the rarity of the central nervous system, as a result of timely and adequate therapy, neurosyphilis has lost its practical significance. However, to date, neurosyphilis, although rare, is found in the practice of both general and forensic psychiatry. Moreover, given the increase in the incidence of syphilis in recent years, an increase in the incidence of neurosyphilis in the future cannot be ruled out if adequate preventive measures are not taken.
Causes of Neurosyphilis
The causative agent of syphilis is pale treponema (Treponema pallidum), belonging to the order Spirochaetales, family Spirochaetaceae, genus Treponema. Morphologically pale treponema (pale spirochete) differs from saprophytic spirochetes (Spirochetae buccalis, Sp. Refringens, Sp. Balanitidis, Sp. Pseudopallida). Under the microscope, pale treponema is a spiral microorganism resembling a corkscrew. It has on average 8-14 uniform curls of equal size. The total length of treponema varies from 7 to 14 microns, thickness – 0.2-0.5 microns. For treponema pallidum pronounced mobility, in contrast to saprophytic forms, is characteristic. It has inherent translational, rocking, pendulum, contractile and rotator (around its axis) movement. With the help of electron microscopy revealed the complex structure of the morphological structure of pale treponema. It turned out that treponema is covered with a powerful cover of a three-layer membrane, cell wall and mucopolysaccharide capsule-like substance. Fibrils are located under the cytoplasmic membrane – thin filaments with a complex structure and causing diverse movement. Fibrils are attached to the end coils and individual sections of the cytoplasmic cylinder using blepharoplasts. The cytoplasm is small-granular, containing the nuclear vacuole, the nucleolus and the mesosome. It was found that various effects of exogenous and endogenous factors (in particular, previously used arsenic preparations, and now antibiotics) had an effect on pale treponema, changing some of its biological properties. So, it turned out that pale treponema can turn into cysts, spores, L-forms, grains, which, when the activity of the patient’s immune reserves decreases, can reverse the spiral-like, virulent varieties and cause active manifestations of the disease. Antigenic mosaic of pale treponem is proved by the presence of multiple antibodies in the serum of syphilis patients: protein, complement-binding, polysaccharide, reagins, immobilizins, agglutinins, lipoid, etc.
Using an electron microscope, it has been established that pale treponema in lesions is more often located in the intercellular spaces, peri-endothelial space, blood vessels, nerve fibers, especially in early forms of syphilis. Finding treponema pallidum in periepinevrii is not yet evidence of damage to the nervous system. Most often, an abundance of treponema occurs with septicemia. In the process of phagocytosis, a state of endocytobiosis often occurs, in which the treponemes in leukocytes consist in a polymembrane phagosome. The fact of treponema imprisonment in polymembrane phagosomes is a very unfavorable phenomenon, since, in the state of endocytobiosis, pale treponemes persist for a long time, protected from exposure to antibodies and antibiotics. At the same time, the cell in which such a phagosome was formed, as it protects the body from the spread of infection and the progression of the disease. This delicate balance can be maintained for a long time, characterizing the latent (hidden) course of syphilitic infection.
Experimental observations N.M. Ovchinnikova and V.V. The delector agrees with the works of the authors, who believe that when infected with syphilis, a long asymptomatic course is possible (if the patient has L-forms of pale treponema) and “accidental” detection of infection in the stage of latent syphilis (lues latens seropositiva, lues ignorata) . E. In the period of the presence of treponema in the body, probably in the form of cyst-forms, which have antigenic properties and, consequently, lead to the production of antibodies; this is confirmed by positive serological reactions to syphilis in the blood of patients without visible clinical manifestations of the disease. In addition, in some patients, neuro-and viscerophilis stages are found, that is, the disease develops as if bypassing the active forms.
Difficult conditions (special environments, anaerobic conditions, etc.) are necessary to obtain a culture of pale treponema. However, cultural treponema quickly lose their morphological and pathogenic properties. In addition to the above forms of treponema, the existence of grainy and invisible filtering forms of pale treponema was assumed.
Outside the body, pale treponema is very sensitive to external influences, chemicals, drying, heating, and the influence of sunlight. On household items, pale treponema retains its virulence until dry. Temperature 40-42 ° C first increases the activity of treponemas, and then leads to their death; heating to 60 ° C kills them within 15 minutes, and up to 100 ° C – instantly. Low temperatures do not have a detrimental effect on pale treponema, and now the storage of treponema in an oxygen-free environment at temperatures from -20 to -70 ° C or dried from the frozen state is a common method of preserving pathogenic strains.
Pathogenesis during Neurosyphilis
The response of the patient to the introduction of treponema pallidum is complex, diverse and not well understood. Infection occurs as a result of the penetration of treponema pallidum through the skin or mucous membrane, the integrity of which is usually broken. However, a number of authors admit the possibility of treponema insertion through an intact mucosa. At the same time, it is known that in the blood serum of healthy individuals there are factors that possess immobilizing activity against pale treponemas. Along with other factors, they make it possible to explain why infection with a sick person does not always occur. Domestic syphilidologist M.V. Milich, on the basis of his own data and analysis of the literature, believes that infection may not occur in 49-57% of cases. The scatter is due to the frequency of sexual contacts, the nature and location of syphilides, the presence of the entrance gate at the partner and the number of pale treponems that have entered the body. Thus, an important pathogenetic factor in the onset of syphilis is the state of the immune system, the intensity and activity of which varies depending on the degree of virulence of the infection. Therefore, not only the possibility of the absence of infection is discussed, but also the possibility of self-healing, which is considered theoretically permissible.
Symptoms of Neurosyphilis
In untreated patients, syphilis lasts for many years. In the classical course of the disease there are 4 periods: incubation, primary, secondary and tertiary.
The incubation period is 20-40 days from the moment of infection until the appearance of a hard chancre.
The primary period lasts from the moment of occurrence of hard chancre to the appearance of generalized eruptions (6-7 weeks).
The secondary period is characterized by generalization of the infection and lasts for 3-4 years. Damage to the nervous system in the secondary period is called early neurosyphilis. Characterized by damage to the meninges and blood vessels (syphilitic meningitis, meningovascular syphilis, syphilitic neuritis and polyneuritis).
The tertiary period develops in 40% of patients in the 3-4th year of the disease and lasts indefinitely. False inflammatory infiltrates in the form of tubercles and gum appear.
Pale treponemas penetrate the nervous system at an early stage of the disease.
Latent (asymptomatic) neurosyphilis is characterized by changes in cerebrospinal fluid (lymphocytic pleocytosis, an increase in protein content) in the absence of any neurological disorders. Latent neurosyphilis is detected more often in the first few years after infection in patients with early syphilis (primary, secondary, early latent).
Acute syphilitic meningitis is a rare condition that manifests itself in the first 1-2 years after infection: headache, nausea, vomiting, meningeal signs. In 10% of cases, simultaneously, maculopapular rash. Fever is often absent. Cranial nerves are often involved (visual, oculomotor, facial, auditory). In the cerebrospinal fluid is detected lymphocytic pleocytosis, increased protein content. Sometimes hydrocephalus develops with intracranial cerebrospinal fluid hypertension and stagnant discs of the optic nerves.
Meningovascular syphilis may develop several months after infection, but more often in the seventh year of the disease. Syphilitic endoarteritis develops in the cerebral vessels of all calibers, causing concentric narrowing of the large arteries, as well as local narrowing or widening of the small arteries. Meningovascular syphilis is manifested suddenly by a clinic of ischemic, less often hemorrhagic stroke. Blood circulation disorders occur in the basin of the middle cerebral artery. A few weeks or months before a stroke, headache, dizziness, sleep disorder, emotional lability, and personality changes are noted. Possible violations in the system of arteries of the spinal cord, such as thrombosis of the anterior spinal artery with the development of Preobrazhensky syndrome (paraparesis, dissociated para-anesthesia, dysfunction of pelvic sphincter organs).
Syphilitic meningomyelitis is characterized by a slowly progressive lower spastic paraparesis, accompanied by impaired deep sensitivity and function of the pelvic organons. Sometimes the symptoms develop acutely and asymmetrically, with features of Brown-Sekar syndrome, which is more characteristic of the thrombosis of the sulcus (the anterior spinal artery).
Dorsalis (tabes dorsalis)
The incubation period is from 5 to 50 years, an average of 20 years. The basis of the dorsal sinuses are inflammatory infiltration and degeneration of the posterior roots in the zone of their entry into the spinal cord and the posterior cords of the spinal cord. Typical symptoms are shooting radicular pains (up to tabetic pain crises), impaired deep sensitivity with loss of deep reflexes and sensitive atexia, neurogenic disorders, impotence. Argyll Robertson syndrome (narrow, irregularly shaped pupils that do not respond to light and with their photoreaction to convergence and accommodation) appears, neurogenic arthropathies (Charcot’s joint), trophic ulcers on the lower extremities are common. All these symptoms may remain after antibiotic therapy.
Progressive paralysis – a late manifestation of infection, usually develops 10–20 years after infection. It is an encephalitic form of neurosyphilis, associated with the direct penetration of treponema from the perivascular spaces into the brain cells, and is manifested by slowly increasing impairments of cognitive functions (memory, thinking) with personality changes up to the development of dementia. Often there are manic and depressive states, delusions, hallucinations. Argayle Robertson syndrome, dysarthria, intentional tremor, decreased muscle tone and muscle strength, dysfunction of the pelvic organs, epileptic seizures are detected in neurological status. The disease progresses steadily, leading to death in a few months or years. Signs of progressive paralysis and spinal dryweed can be combined, in such cases, diagnosed with taboparish.
Syphilitic gumma can be localized in the area of the basal CSF and lead to compression of the cranial nerves on the basis of the brain. The clinical picture is reminiscent of signs of extensive brain damage with progressive intracranial hypertension. Sometimes the gumma is localized in the spinal cord, causing increasing lower paraparesis, paragipesthesia, dysfunction of the pelvic organs.
Diagnosis of Neurosyphilis
In addition to the typical clinical picture of various neurosyphilis variants, the leading diagnostic method is serological (Wasserman reaction, precipitation microreaction with cardiolipin antigen, immunofluorescence reaction – RIF, treponem immobilization reaction – RIT). In general, the diagnosis of neurosyphilis requires 3 criteria:
– positive non-treponemal and / or treponemal reactions in the study of blood serum;
– neurological syndromes characteristic of neurosyphilis;
– changes in cerebrospinal fluid (positive Wasserman, inflammatory changes in the cerebrospinal fluid with cytosis of more than 20 μl and a protein content of more than 0.6 g / l, positive REEF).
CT and MRI of the brain in neurosyphilis reveal nonspecific changes (increased contrasting of the meninges, heart attacks, multifocal lesions of the white matter, hydrocephalus, gum, brain atrophy) and serve mainly to exclude other diseases.
It is necessary to differentiate with serous meningitis of another etiology, vasculitis, sarcoidosis, tick-borne borreliosis, brucellosis, etc.
The most effective intravenous administration of high doses of penicillin (2-4 million ED 6 times a day) for 10-14 days. Intramuscular administration of penicillin does not allow to achieve a therapeutic concentration in the cerebrospinal fluid and is possible only in combination with oral ingestion of probenicide (2 g per day), which delay renicin penicillin. If you are allergic to penicillins, ceftriaxone (rocephin), 2 g per day, is used by intravenous route or intramuscular injection for 10-14 days.
In the first hours after the start of treatment, acute fever, chills, tachycardia, a decrease in blood pressure, headache and myalgia (Yarish-Herxheimer’s reaction), a deepening of existing neurological syndromes can occur. Usually these symptoms regress during the day, corticosteroids (60 mg of prednisone) and non-steroidal anti-inflammatory drugs contribute to this.
The criteria for the effectiveness of treatment of neurosyphilis are regression or the absence of progression of neurological symptoms, and normalization of the composition of cerebrospinal fluid. Lumbar puncture and research of the CSF is repeated every 6 months. for 2 years. If by this period the cytosis is preserved or new ones appear or neurological symptoms are growing, then a repeated course of treatment is recommended.