SU1765767A1 - Method of diagnosis of nervous system damage in leukosis - Google Patents

Abstract

The invention relates to medicine, in particular to methods for diagnosing a lesion of the nervous system in patients with leukemia. The purpose of the invention is to reduce mortality, increase life expectancy and remission. SUMMARY OF THE INVENTION: The method involves determining a number of basic clinical and liquor diagnostic criteria for affecting the nervous system at the same time in various ways: by history, the absence or presence of headaches, fever and other complaints, the appearance and development of symptoms; by neurological examination - symptoms of symmetrical or asymmetrical, diffuse, focal, multifocal or combined lesions of the vascular-epithelial plexus, membranes and substances of the brain and spinal cord, roots or terminal branches of nerves; by liquorodiagnostics, there is also the absence or presence of xanthochrome and other changes in the color of the cerebrospinal fluid, pleocytosis, leukemic, immuno-competent and macrophage cells, and most importantly immunoblasts, polyblasts, erythrophages, pigment phages, erythrocytes with their quantitative assessment the first and after portions of the liquor; The severity of symptoms, the course and dynamics of the process before and after treatment are also determined. At a certain ratio of the specified diagnostic criteria, patterns, clinical and liquor comparisons, the type of lesion in the nervous system is diagnosed. sl C

Description

The invention relates to medicine, in particular to diagnostic methods in neuropathology and hematology.

A known method for the liquor-logical diagnosis of lesions of the nervous system (NS) is determined by microscopic determination of cerebrospinal fluid (CSF) and cystic blast cells.

At the same time, the diagnosis of neuroleukemia is established when cytosis above 10 is found in 1 μl of necessarily blast cells in CSF.

However, this method does not allow differential diagnosis of NA lesions in patients with leukemia, type and

a variant of cellular infiltration of its formations, including leukemia proliferation, referred to in the literature as neuro-leukemia or neuroleukemia.

The purpose of the invention is the early differential diagnosis of NA lesions with cellular infiltration of its lesions in patients with leukemia, increased life expectancy and remission, reduced mortality. This goal is achieved through a comprehensive simultaneous and dynamic examination of the patient with special clinical neurological and laboratory liquorological diagnostics methods.

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ABOUT

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The method is carried out as follows.

The patient is simultaneously determined

by anamnesis, algesimetry and thermometry - the absence or presence of complaints, especially headache and increased body temperature, time of appearance and development (acute 0.05 ± 0.02 months; subacute 0.3 ± 0.2 months, and gradual 1,5 ± 0,5 months.). It is necessary to get answers to the specific questions indicated, since leukemia patients complain to a neurologist, as a rule, do not present or pay attention to symptoms that are not important for the differential diagnosis of various types and variants of cell infiltration of NA;

by special clinical neurological examination of the patient — localization of the process (the substance of the brain, its sheath and vascular epithelial plexus, the substance of the spinal cord and its sheath, the roots of the cranial and spinal nerves, their terminal branches): focal, diffusive or focal diffusion; symmetrical or asymmetrical; one way or two way Attention is drawn to the main clinical neurological manifestations, which, for each type and variant of cell infiltration of NA in patients with leukemia, are determined by the localization of the process, which, in turn, determines certain morphofunctional properties of the nervous system. So, for example, bilateral and symmetrical damage to the roots of the YI-XII pair of cranial nerves with mild bilateral pyramidal insufficiency, which is observed with proliferation of the anomalous cells, can only be in the area of the nervous system where it is named. The anatomical structures are located together and compactly. And this is the region of the medulla oblongata, where the roots of the YI – YIII pair and on the border of the oblong brain of the IX – XII pairs of cranial nerves emerge on the border of it with the ponsidium bridge. In the medulla oblongata there are pyramids - the crossroads of pyramidal paths. These formations occupy an area of dimensions: longitudinal 3 cm, transverse on average up to 1.5 cm, anteroposterior up to 1 cm. Therefore, these clinical neurological symptoms can only be the manifestation of proliferative proliferative type leukemic infiltration localized in the IY ventricular epithelial soft shells covering its plexus, the medulla and the roots of these nerves in

type of coupling. Therefore, proliferating leukemia cells can accumulate in these structures and, with a large cluster, slightly compress the pyramids of the medulla oblongata, but do not infiltrate it. A pronounced compression of loose leukemic infiltration can not cause. That is why, with the proliferation of leukemic cells, not one patient had and cannot have

0 neither paralysis, nor paresis of the extremities, but only easy bilateral pyramidal insufficiency. On the other hand, leukemic proliferation in the brain substance is extremely difficult and practically cannot arise due to the lack of favorable conditions in it for the accumulation and proliferation of leukemic cells due to their high vulnerability and instability, and most importantly morphofunctional features

0 capillaries and perivascular spaces in the brain substance, the width of which reaches 200 A, Leukemia cells in the brain substance cannot proliferate due to the lack of sufficient cells in it

5 sizes of perivascular spaces, and as a result of their death due to the presence of natural killer cells in the CNS. In reality, leukemia occurs and develops in the substance of the brain.

0 infiltration is not of the proliferative type, but of the impregnation type, caused by the impregnation process both in the inhibition of the immunoreactivity of the brain, its immune barrier, and in the pathological immune reaction, the breakdown of the strength of the hemato-encephalic barrier (BBB), the hemostasis system, nervous, immune and other mechanisms of its regulation under the influence of not only leukemic, but also infectious,

0 toxic, allergic and other pathological processes.

Attention is also paid to clinical neurological microsymptomatics, since only the abductor is a minor deficiency — the YI pair of cranial nerves in the absence of other symptoms of HC lesion can be a manifestation of proliferative leukemic infiltration of the proliferative type in the sheath of the basement and the vascular epithelial plexus IV ;

by liquor diagnosis, the absence or presence of changes in the color of the cerebrospinal fluid, especially xanthochromia; pleocytosis,

5 leukemic and immunocompetent cells, polyblasts, macrophages, erythrophages, pigment phages and erythrocytes, identify them from the subarachnoid space from the admixture of artifactual blood. Leukorrhea patients also have their significant differences, as well as clinical diagnostics. CSF is extracted only under the mandrel due to edema of the brain that is often observed in these patients, hypertension syndrome, infiltration of central nervous system formations by peripheral blood cells and pathological immune response such as immune inflammation. CSF sampling was not performed in one, but in 4-5 tubes. This is necessary to prove that the red blood cells have penetrated into the subarachnoid space due to the formation of cellular infiltration of the nervous system, such as impregnation, and are not the result of artifactual blood admixture in the CSF. When erythrocytes penetrate into the subarachnoid space from cell infiltration such as soaking, the color and transparency of the CSF are the same in all tubes, and when the blood is added to the CSF in the first tube pink, in the last tube it is colorless and transparent. The study of CSF is performed in the first minutes after its extraction, which is caused by the rapid destruction of its cellular composition, and it is necessary in the first and last portions. Erythrocyte counting was done microscopically in the Gorev chamber. Evidence that the red blood cells from the subarachnoid space, is the equal number of them in the first and last portions of the CSF or even more of them in the last portion. In the case of arithmetic blood admixture in the CSF, the number of erythrocytes in the first portion is several times greater or they may even be absent in the last portion. The presence of erythrophages and pigment phages in the CSF is direct evidence that the erythrocytes have penetrated into the subarachnoid space from the cell infiltration type of impregnation. It is very important to detect macrophages, monocytes, polyblasts and other cells of the macrophage system in the CSF, especially in cases when erythrocytes in cell infiltration, such as soaking, are already destroyed or when their penetration into the subarachnoid space is difficult. The presence in the CSF of cells of the microphagal system and erythrocytes, even with normal cytosis, indicates the occurrence of cell infiltration of the type of impregnation, as well as the limitation periods of occurrence, course, dynamics and degree of impregnation of the impregnation process in the CNS formations.

Morphological liquor diagnosis of patients with leukemia also has its own characteristics. Deposition of CSF cells by centrifugation is not recommended due to their rapid destruction, it is better to use the Bunny sedimentation method. Cytosis is determined in a Fuchs-Rosenthal chamber.

Cell morphology and cerebrocytogram are determined simultaneously in both the native (Funck-Rosenthal cell) and colored preparations. Cell fixation and staining of CSF preparations are made with paint

Leishman not more than 1 min, otherwise the identification of cells will be significantly difficult. If pleocytosis exceeds 1010 cells / l, then in the liquorocytogram, the percentage ratio of its cellular composition is given, while

pleocytosis less than 100-U6 cells / l, the content of cells of different nature is given in absolute units. When determining the percentage of the cellular composition of the CSF, despite low cytosis, it is indicated how much CSF contains 100 cells, otherwise the definition of the cytogram will be incorrect.

As can be seen, this diagnostic method excludes other, more complex and expensive methods of identifying CSF cells. if even leukemic cells are identified with exceptional accuracy, they can be not only a consequence of the formation of leukemic infiltration of a proliferative type, but also a type of impregnation and a combined type. Diagnostic criteria for the occurrence of leukemic infiltration such as impregnation are liquorological indicators such as spectrophages, pigment phages and other macrophages and erythrocytes, even if they are single in any cytosis, and in the absence of the indicated indicators clinical neurological manifestations are decisive in diagnosis.

which only determine this infiltration option and no other;

the above clinical neurological and liquorological diagnostic indicators in dynamics, before and after

treatment; pay attention to the degree of their severity (mild, moderate, severe), the absence or presence of dissociation between clinical neurological and liquorological manifestations (dissociation between lungs, clinical neurological and expressed liquorological indicators of the character for leukemic infiltration of proliferative type, while dissociation

between severe clinical neurological and lung liquorological indicators (characteristic of cellular infiltration of proliferative type from macrophage and lymphoid immunocompetent system cells); flow (progressive, remitting, progressive remitting, regressing).

On the basis of the data obtained, with appropriate laws of clinical-liquorological correlations, HC lesions of various types and variants are diagnosed.

PRI me R 1. Patient T., 18 years.

Diagnosis: acute lymphoblastic leukemia, developed stage, relapse 1, with leukemic infiltration of the proliferative type in the membranes of the predominantly brain base, mild bilateral and symmetric damage to the oculomotor and caudal groups of the cranial nerves, mild pyramidal insufficiency and moderate astheno-vegetative syndrome.

Anamnesis. No complaints, headaches and fever denied. The diagnosis of acute lymphoblastic leukemia was established six years ago on the basis of hemomyelogram.

Neurological examination: a study of the cranial brain innervation revealed mild insufficiency of the oculomotor nerves, more pronounced on the left, in the form of mild ptosis of the upper eyelids, limiting the movement of the ocular block inside and diplopia on the view of the eye. There was also a slight limitation of the movement of the eye blocks outwards and of the diplopies upon looking outwards — as a manifestation of the insufficiency of both of the abduction nerves; the smoothness of the folds of the folds and the slight asymmetry are a consequence of the slight insufficiency of the facial nerves; reduction of the reflex during irritation of the pharyngeal wall, slight choking when swallowing, hoarseness is insignificant, indicating a lack of pharyngeal nerve. In the study of the motor sphere, an increase in tendon and periosteal reflexes and a Babinsky symptom from two sides were revealed. Body temperature 36.2 °.

According to lymphoblasts hemogram 55%, according to myelogram lymphoblasts 93%.

Preliminary clinical diagnosis. After detoxification and antiedematous therapy, lumbalon puncture was performed.

Liquorodiagnostics: liquor pressure 1225 hPa, 6 ml of liquor were extracted under mandrin in four tubes; CSF in all tubes is colorless, transparent. CSF microscopy: cytosis in the first and last portion of 300-106 cells / l, the morphological picture is represented by leukemic cells, some in the stage of mitosis. Erythrocytes, erythrophages and pigment phages were not detected.

After treatment: detoxification therapy in the form of transfusion-renal formed diuresis before endolumbic administration of methotrexate at a dose of 10 mg / m at intervals of seven days. In the course of treatment, on the second day, partial treatment began, and after ten days from the start of treatment, a complete regression of clinical neurological manifestations occurred. The cytosis before the third administration of methotrexate 25-10 cells, / l, the cells were destroyed, and a month after the last administration of methotrexate, the cytosis was 3-106 cells, / l, lymphocytes. For five months, the patient was not treated, and against the background of a pronounced progression of the leukemic process (according to the hemogram of lymphoblasts 75%), the above symptoms of mild failure III, YI, YI and IX were again detected during clinical neurological examination cranial nerves and bilateral pyramidal insufficiency. Body temperature 36.3 °.

Liquorodiagnostics: CSF is transparent, colorless, Microscopy in the first and last portions: pleocytosis of 3584-106 cells / l,

the morphological picture is represented by leukemic cells, some in the stage of mitosis; Erythrocytes, erythrophages, pigment phages and other macrophages were not detected. After endolyumbal administration of methotrexate at a dose of 10 mg / m, five injections, a complete regression of clinical neurological manifestations occurred. Cytosis after the second endolyumbal administration of methotrexate 40-106, one month after the last 6-U6 administration, after two months of 3-106, and four months after the endolyumbal administration of methotrexate 2-U6 C / l. The morphological picture is represented by lymphocytes; red blood cells are not detected.

The proliferation of leukemic cells was not detected for the whole subsequent life of more than 10 months.

Thus, with the clinical and liquor diagnosis by anamnesis,

neurological examination, determination of the color and cytosis of CSF, microscopy of its cellular composition with liquorocytogram and the detection of erythrophages, pigment phages and erythrocytes, their quantitative assessment in

The first and last portions of this patient with acute lymphoblastic leukemia identified the following diagnostic criteria for leukemic infiltration of proliferative type:

clinical neurological symptoms of symmetric lesions of the formations on the basis of the brain, mainly the vascularistoepithelial plexus of the IY ventricle and membranes covering the roots of the cranial nerves, in the form of bilateral pyramidal insufficiency and radicular syndrome of the eye-moving, retractable, facial and pharyngeal nerves of mild severity, post - foam development (in case of recurrence of leukemic infiltration of a profiled type, its clinical manifestations appeared only after five months;

liquorological indicators - pronounced pleocytosis -300 and 3584-10 cells / l of leukemic cells, some of which are in the stage of mitosis;

progressive course without treatment and regressing with optimal anti-leukemia therapy;

The absence of anti-relapse therapy led to the appearance of the same clinical neurological and liquorologic symptoms of lesions on the basis of the brain, which were identified during the initial occurrence of proliferative leukemic infiltration by clinical and liquorologic diagnosis;

clinical and liquorological data, revealed in dynamics, confirm the validity of the diagnosis established during the initial clinical and liquor diagnosis;

the pattern of clinical-liquorologic relationships in the form of dissociation between unexpressed symptoms of symmetrical lesions of formations mainly on the basis of the brain, clinically manifested by mild bilateral pyramidal insufficiency and insufficiency of III, VI, VII, IX pairs of cranial nerve on the background of normal body temperature and pronounced pleocytosis 3584-10 cells / l of leukemic cells, partly in the stage of mitosis.

Diagnosis of the specified option infiltration reliable in 100% of patients (in the prototype, only 3 (18.6%) patients).

PRI mme R 2. Sick D., 58 years.

Diagnosis: acute myeloblastic leukemia, initial stage (remission according to hematological parameters) with cellular infiltration of proliferative-type CNS from the cells of the macrophage and lymphoid immunocompetent systems under the influence of the infectious process, infectious meningopoli-diculoneuritis with

pronounced liquorodynamic disorders and disadaptation syndrome.

Anamnesis. Complaints about sharp head

pains in the right half and in the occipital region, numbness and weakness in the left leg, in the cysts and feet, an increase in body temperature to 38 °, which appeared during ARI, bronchitis and hepatitis. Hemogram in

This period is within the normal range. A month after the onset of neurological manifestations, a diagnosis of acute myeloblastic leukemia was made on the basis of a myelogram. Against the background of cytostatic therapy of HC

5 progressed, headaches intensified, numbness and weakness in the left leg, in the cysts and in the feet to pronounced. The body temperature continued to rise.

Neurological examination: conscious,

0 however, it is inhibited, moaning from marked pains in the right half of the head, occipital region and extremities against the background of an extremely severe general condition. Severe pain at the exit points of the branches of the triple and occipital nerves on the right, spinal roots and along the nerve trunks. Innervation insufficiency of the caudal group of the cranial nerves on the right and spinal nerves, more pronouncedly - the left sciatic nerve. Against the background of hypoesthesia of the root type at the level of L.2 - 3h of the segments, the hypostezia of the polyneuric type was revealed. Expressed vegetative-vascular reactions with

5 asymmetry. HELL on the left 160/100, on the right 140/120 Significantly reduced reserve adaptation.

Hemogram: hemoglobin 113 g / l, leukocytes 4.3-10 cells / l, platelets 250x

0 хЮ9 Cl, / l, ESR 7 mm / h. Leukocyte formula,%: metamyelocytes 0.5, bacillus 19, segmentodicular 52.5, eosinophiles 5, basophils 0.5, lymphocytes 18, monocytes 4.5. Myelogram without pathology.

5Preliminary clinical diagnosis.

Detoxification, anti-infectious (antibiotics), anti-inflammatory, analgesic, desensitizing and general strengthening therapy were urgently carried out, after which the general condition improved significantly. The body temperature dropped to 37.8 °, the adaptation margin increased, the arterial balance became symmetric

5 Sd 130/90 pressure, improved mood, decreased pain syndrome, however, motor and sensory disorders of the radicular type were unchanged.

Liquorodiagnostics: liquor pressure 2450 hPa. Under mandrin removed 8

ml of CSF in five tubes, CSF is colorless and transparent in all tubes. Cytosis in the first and last portion of 10-10 cells / l. Microscopic - morphological picture is represented by monocytoid and lymphoid polyblasts, lymphocytes and macrophages. Red blood cells are not detected.

Guided by the conventional method, a diagnosis of neuroleukemia (leukogen proliferation in the brainstem) was established and endolyumbal administration of cytostatic agents was prescribed. But with the introduction of metrerexate, even at a dose of 10 mg / m, the general condition worsened, the general cerebral symptoms and polyradiculoneurotic syndrome increased, the cytosis in the CSF increased to 18-106 cells / l. Liquorocytogram,%: polyblasts 6–13, granulocytes 6, eosinophiles 6, lymphocytes 56, plasma cells 4, macrophages 8. With repeated administration of methotrexate after seven days, the cytosis increased to 22-106 cells / l. Liquorocytogram,%: polyblasts 3, 5, monocytes 9, 5, lymphocytes 82, macrophages 4, 5, plasma cells 0.5. In addition, there was an increase in the existing neurological manifestations, while at the time of the proliferation of leukemic cells in the formation of the CNS even after the first endolyumbal administration of methotrexate, as a rule, it was noted with a significant regress of neurological manifestations. Therefore, cytostatic agents were canceled and the treatment was continued as described above. After 15 days, there was a significant regression of neurological manifestations, cytosis was reduced to 6-U6 cells / l, and after 1 month their complete regression. The clinical and liquor index of reissi lasted until the end of life, for 10 months, without the use of cytostatic agents. . The fatal outcome came from liver failure.

Thus, the following diagnostic criteria for cell infiltration of proliferative NA of the proliferative type from the cells of the macrophage and immunocompetent systems under the influence of infection were identified according to the patient with acute myeloblastic leukemia:

clinical neurological symptoms of asymmetric pronounced damage to the roots of the cranial and spinal nerves, mainly trigeminal and occipital, on the right and sciatic, on the left;

liquorological indicators - low pleocytosis (10-U6 cells / l) from the cells of the macrophage and lymphoid immune system, mainly polyblasts;

regressive course in the suppression of the infectious process and progressive with the use of cytostatic agents; enhancement of clinical neurological manifestations, increased pleocytosis from cells of the macrophage and immunocompetent system;

Clinico-liquorological data, revealed in dynamics, confirm the accuracy of the diagnosis established at the primary clinic - liquorological diagnostics;

regularity of clinical-liquorologic relationships in the form of dissociation between the pronounced symptoms of asymmetric damage to the roots of the cranial and spinal nerves against the background of high body temperature and unexpressed pleocytosis (10-U6 cells / l) from the cells of the macrophage and lymphoid immunocompetent system.

Diagnosis of the specified variant infiltration is reliable in 100% of patients (in the prototype unreliable in 100% of patients).

PRI me R 3. Patient H., 18 years.

Diagnosis: acute lymphoblastic (since 1983) and myeloblastic (since 1986) leukemia, developed stage, relapse II, with cell infiltration of NS proliferative type from the cells of the macrophage system under the influence of the toxic process, mild organic symptoms, moderate liquorodynamic disorders, moderate asthenic-vegetative syndrome, and toxic polyneuropathy.

Anamnesis. Complaints of short-term headaches after intravenous administration of L-asparaginase, an increase in body temperature of 37.5 °; numbness of fingers and toes, coldness and sweating.

These symptoms appeared after 29 months from the detection of acute leukemia, initially treated as a lymphoblastic variant: in the myelogram from 26.08.1985, lymphoblasts 79.8%, and from 07.04.1986 - myeloblasts 82.2%; according to a cytochemical study of 06/16/1986, myeloid-type blast cells.

Neurological examination. The study of craniocerebral innervation revealed a weakening of convergence, slight asymmetry of the nasolabial folds; spinal innervation - lack of Achilles and plantar reflexes, hypesthesia of the hands and feet. Blood pressure on the left is 140/90, on the right 120/80, hyperhidrosis of the palms and feet, moderate decrease in the reserve of adaptation.

Preliminary clinical diagnosis. Detoxification, desensitization, tonic and anti-inflammatory therapy was carried out, after which the general condition of the patient improved significantly, vegetative-vascular reactions normalized, blood pressure became symmetrical (120/80); increased stock adjustment; however, manifestations of polyneuropathy in the form of motor and sensory impairments are unchanged.

Liquorodiagnosis: liquor pressure 1200 hPa. Under the mandrin, 2 ml of CSF were extracted into five test tubes, the liquor is transparent and colorless in all portions. In the first and last portions of pleocytosis 135-U6 cells / l; microscopes: the morphology of the cellular composition of the CSF is presented by monocytes, macrophages and single lymphocytes; erythrophages, pigment phages and erythrocytes were not detected. With repeated liquor diagnosis after 22 days, cytosis is 3-U6 cells / l and is represented by lymphocytes. Clinical manifestations also regressed completely. According to clinical and liquorological indicators, remissi lasted for 10 months, until the end of life, the cytosis did not exceed 1-2 cells / µl. The patient was active, continued to work in his profession as an electrician, and then served himself until the end of life. Death ensued from intoxication.

Thus, the following diagnostic criteria for cell infiltration of a proliferative type NA from the cells of the macrophage system under the influence of the toxic process were identified by the patient with acute leukemia:

clinical neurological symptoms of diffuse NA lesions in the form of dissipated organic symptoms, hypothalamic insufficiency and polyneuropathy, developed against the background of intensive polychemotherapy;

liquorological indicators - predominantly macrophage pleocytosis - 135-10 cells / l, corresponding to the degree of intoxication, in this patient is moderate;

progressive course without treatment and regressing in suppressing the toxic process;

the clinical and liquorological data, revealed in dynamics, confirm the accuracy of the diagnosis established during the primary clinical and liquor diagnosis;

pattern of clinical-liquor-logical relations: moderate headaches

moderate macrophage pleocytosis corresponds to scattered organic symptoms, moderate hypothalamic insufficiency and polyneuropathy

135-U6 cells / l.

Diagnosis of the specified variant infiltration is reliable in 100% of patients (in the prototype unreliable in 100% of patients). PRI me R 4. Patient T., 30 years.

Diagnosis: acute myeloblastic leukemia, developed stage, relapse II, with cell infiltration of proliferative-type CNS lesions from cells of the lymphoid immunocompetent system, aseptic allergic leptomeningitis with liquorodomycic disorders and marked astheno-vegetative syndrome, edema and nasal pharynx, swelling and nasal pharynx, and swelling and nasal pharynx;

Anamnesis. Patient's complaints of mild headaches with a single vomiting, gagging when eating, hoarseness, pain in the eyes, unstable doubling, severe pain in muscles, especially the neck and back.

These symptoms appeared after the third injection of an immunopreparation, administered prophylactically once a week intracutaneously, and after 9 months. from the manifestation of acute leukemia.

Neurological examination. Consciousness is clear, adequate, critical, asthenized; pronounced pasty face, sclera injected. The movement of the ocular block in full, non-circulation of diplopia, easy

smoothness of the right nasolabial fold. The pharyngeal reflex is alive. Swelling of the oral mucosa, nasopharynx, hoarseness. There are no motor, sensory, radicular and coordinating disorders, severe pain on palpation of the muscles of the neck, shoulder and shoulder, and back. Moderate stiff neck. Spilled red resistant dermographism. Blood pressure on the left

80/55, right 90/60, temperature 36.3- 36.9 °. Significantly reduced stock adaptation. Hemogram data: hemoglobin 141 g / l, erythrocytes 4.17-1012 cells / l, leukocytes 10.3-10 cells / l, platelets

190-Yu9 cells / l, ESR 5 mm / h. Leukocyte formula,%: myeloblasts 14.5, promyelocytes 1.5, myelocytes 4, bacillus 27.5, segmentometric 28, eosinophils 1.5, basophils 0.5, lymphocytes 1.5, monocytes 3.5.

According to myelogram myeloblasts 39%. Preliminary clinical diagnosis. Canceled immunopreparations. Immediately introduced desensitizing, detoxifying, toning and decongestant

funds. After 40 minutes, the patient's condition improved significantly. The gagging, hoarseness and diplopies almost disappeared,

Likvorodiagnostika. Liquor pressure 2940 hPa. Under the mandrin, 8 ml of cerebrospinal fluid was extracted into five test tubes, transparent, colorless in all portions. In the first and last portion, cytosis was determined - 1000-106 cells / l. Microscopy: the morphological picture is represented by various cymphocyte populations, erythrophages, pigment phages, erythrocytes were not found.

After 0.3 months from the start of treatment, adequate to the diagnosis, a complete regression of these symptoms began, diplopia completely disappeared, which was due to edema of the periocular tissue, and not damage to the oculomotor nerves, as well as poking and hoarseness, which were caused by swelling of the pharynx, and not defeat of the pharyngeal pharyngeal nerves; Cytosis was 2-10 cells / l from lymphocytes and macrophages. However, by the guidance of the generally accepted diagnostic method, a diagnosis of neuroleukemia (leukemia proliferation in the brainstem) was made, and despite a complete regression of the clinical and liquorologic symptoms, treatment was started by the conventional method (with a reliable administration of methotrexate at a dose of 12.5 mg / m and cytosarses 10-50 mg / m2), against which numbness of the right extremities and half of the body appeared, and in CSF erythrocytes, Dynamics of cytosis, cell and erythrocyte morphology: 1-106 cells / l (single white blood cells and erythrocytes); 8-10 cells / l (single blast cells, large numbers of red blood cells); 7–10 ° C / l (single blasts, mature lymphocytes, red blood cells in large quantities in the first and last portions). After the next endolyumbal administration of these drugs during the morning when he got out of bed, a slight right-sided hemloresis developed. In CSF on the seventh day of acute violation of cerebral blood circulation-t xanthochrome, cytosis (8-U6 cells / l) / erythrocytes (1820-U 6 cells / l). Nevertheless, the endolyumbal administration of cytostates of the drugs was continued, and after 2.5 months. from the beginning of their introduction there was a lethal outcome. In the section of leukemic proliferation, neither in the brainstem nor in other formations of NA was detected. Cause of death intoxication.

Thus, according to the patient's method of acute myeloblastic leukemia, the following diagnostic criteria for cell infiltration of a proliferative type NA from the cells of an immune-competent system under the influence of an immunopreparation were identified:

5clinical neurological symptoms of diffuse irritation of the morphological substrate of the brain's immune barrier in the form of meningeal syndrome; diplopia due to edema

0 fiber, choking and hoarse voices caused by swelling of the nasopharynx and larynx, which imitated the defeat of the roots of the oculomotor and pharyngeal nerves;

5 liquorological indices - pleocytosis 100010 cells / l from lymphocytes of various degrees of maturity;

a progressive course against the background of the introduction of cystostatic and immune preparations and regressive in suppressing the immune process, detoxification, desensitizing and anti-edema therapy;

clinical and liquor data

5 identified in the dynamics, confirm the accuracy of the diagnosis established during primary liquorodiagnosis;

pattern of clinical and liquorological correlations; severity

0 diffuse irritation of the morphological substrate of the brain's immune barrier in the form of moderate meningeal syndrome corresponds to pleocytosis 1000-106 cells, / l from lymphocytes of varying degrees of maturity,

Diagnosis of the specified variant infiltration is reliable in 100% of patients (in the prototype unreliable in 100% of patients).

0 PRI me R 5. Ill H ,, 18 years.

Diagnosis: acute lymphoblastic leukemia, T - cell variant, developed stage, with cellular infiltration of proliferative CNS lesions from uninfectable and immunocompetent cells, mild organic symptoms, moderate lymphocytic disorders and moderate asteno-vegetative syndrome. Neuritis

0 left facial nerve of combined genesis.

Anamnesis. Complaints of recurrent unsharp headaches that occur during fatigue and after taking medication,

5, especially with endolyumbal and intravenous administration, which appeared after neuroleukemia prophylaxis (endolyumbal administration of methotrexate), resulting in cytosis in the CSF began to increase from 3-106 (lymphocytes) to 53-10 cells / l, the morphological picture was represented by unidentifiable cells (88 %) and lymphocytes (12%). In addition, against the background of cooling, acute respiratory infections and increased body temperature, paresis of the left facial nerve was acutely developed.

Neurological examination. A study of craniocerebral innervation revealed peripheral-type symptoms of lesion of the left facial nerve. Organic symptoms are easily dispersed. Preliminary clinical diagnosis.

Detoxification and anti-inflammatory therapy was carried out, after which the headaches disappeared, the general condition improved. However, the management of the generally accepted diagnostic method has been diagnosed with neuroleukemia (leukemia proliferation in the brainstem) and has been prescribed treatment in the conventional way. But the endoluminal administration of methotrexate, even at a dose of 10 mg / m, led to an increase in neurological manifestations and an increase in pleocytosis. So, on 09/26/1986, the cytosis was 10-10 cells / l. Morphological picture in the preparation,%: unidentifiable cells 22, neutrophils 1, monocytes 17, lymphocytes 8, plasma cells 2. After endolumbular administration of methotrexate cytosis 02.10.1986. was 14-106 cells / l. The morphological picture in the preparation,%: monocytes 32, basophils 1, lymphocytes 58, macrophages 4, plasma cells 5. In addition, cytosis in the CSF was increased by the introduction of cytostatic drugs and in other ways; after lymphoblasts (53%) and thrombocytopenia (120-U6 cells / l from November 25, 1986) appeared in the peripheral blood against the background of intensive polychemotherapy, while in myelogram from 14,10.1986 g, there were no lymphoblasts in general, while myeloblasts were only 1.8%. Due to the progression of the disease, due to the use of the conventional method, treatment was continued, adequate to the above-stated dianosis, after which a complete regression of symptoms of CNS damage occurred after 0.25 months, the appearance of facial nerve paresis continued to remain. In the control study of CSF of December 22, 1986, the cytosis was 1–106 cells / l. The following clinical and liquorological diagnostic criteria were identified for diagnosing a patient with acute lymphoblastic leukemia (T-cell variant):

clinical neurological symptoms of diffuse perivascular disorder of NA spaces in the form of dispersed organic symptoms;

liquorological indices - pleocytosis of 63-U6 cells / l from unidentifiable cells (88%) and lymphocytes (12%);

progressive course with intensive cytotic therapy and regressing with treatment that is adequate to the established diagnosis by clinical and liquorological method;

clinical and liquor data

0 revealed in dynamics confirm the accuracy of the diagnosis established by clinical-liquor-logical method;

The pattern of clinical-liquor-logical correlations: symptoms of diffuse lesion of the perivascular spaces of the nervous system in the form of dispersed organic symptoms correspond to pleocytosis 63-10 cells / l from unidentifiable cells and immunocompetent cells.

Diagnosis of the specified variant infiltration is reliable in 100% of patients (in the prototype unreliable in 100% of patients). Example Sick K., 44 years old.

5 Diagnosis: acute lymphoblastic leukemia, unfolded, recurrent II, with thrombocytopenia, cell infiltration of the type of impregnation in the area of the membranes and the convexital surface of the brain substance, brain edema, right-side faciolingo-brachial syndrome, scattered with organic symptoms, liquorodynemoid, and , crises of sympathoadrenal and vaginal character, disadaptation syndrome and remitting course.

Anamnesis. Complaints of chills, general tremors and convulsions, non-systemic nature of dizziness, double vision, noise in

0 to the left ear, an increase in blood pressure, which arose sharply against the background of a significant psychological overvoltage after seven months. from the manifestation of acute leukemia. These symptoms spontaneously reacted for four days, but after 20 days, amid emotional stress, the right side of the face, right limbs, more pronounced in the arm, and

0 by the difficulty of speech, which lasted for several minutes, and the difficulty of speech and the attacks of seizures either in the right or in the left extremities were periodically repeated. Neurological examination after 28 days

5 from the occurrence of the first symptoms of a CNS lesion: consciousness is clear, actively comes into contact, adequate, asthenized, emotional. Convergence, nasolabial fold asymmetry, dizatri weakened. Tendon and periosteal reflexes

average liveliness. Right spontaneous extension of the big toe. Uncertain implementation of coordinated samples. The right-sided hemihypesthesia is easy, more pronounced on the face and arm. HELL left 115/80, right 130/90. Significantly reduced stock adaptation. Hemogram data: hemoglobin 65 g / l, erythrocytes 3,9-U12 cells / l, leukocytes 3,1-10 cells / l, platelets 90-U9 cells / l, ESR 10 mm / h. Leukocyte formula,%: promyelocytes 0.5, myelocytes 0.5, eosinophils 4, lymphoblasts 7, lymphocytes 60.5, monocytes 0.5. Myogram,%: lymphoblasts 59.2, lymphocytes 20.6, cells of the neutrophilic range 7.4, cells of the erythroid range 9.8.

Preliminary clinical diagnosis.

3 hours after hemostatic, detoxification and general strengthening therapy, the general condition of the patient improved significantly, the attacks described above were stopped.

Liquorodiagnostics: liquor pressure of 1960 hPa. Under mandrin, 6 ml of liquor was extracted into four tubes, the cerebrospinal fluid was clear, xanthochromic, the color and transparency were the same in all four tubes. Microscopy: cytosis of 533-106 cells / l, the morphological picture is represented by lymphoid cells; red blood cells (the same large amount in both portions).

The presence of xanthochromia and erythrocytes in the cerebrospinal fluid indicates the accuracy of the diagnosis, established on the basis of clinical neurological symptoms, which continued to regress during therapy, adequate to the above diagnosis.

However, by the guidance of a generally accepted method, the diagnosis was made: neuroleukemia (leukemia proliferation in the brainstem) and, despite the improvement in the patient's condition, the continued regression of the symptoms of the membranes and substance of the brain and the contraindication of the endolyumbal administration of cytostatic perparates by the conventional method, endole .albal administration of methotrexate at a dose of 12.5 mg / m at intervals of 2-3 days. Lymphoid pleocytosis in the CSF was doubled (942-106 cells / l), the color of the cerebrospinal fluid in all tubes is the same, pale pink. Microscopy: the number of erythrocytes in the last portion significantly exceeds their content in the first portion. High pleocytosis (942–10 cells / l) was regarded as a result of enhanced proliferation of leukemia cells in the brainstem, and endolyumbal administration of cystostatic drugs continued until death, which occurred after 0.5 months. from the beginning and 40 hours after the last endolumbial administration of cytotoxic drugs.

At the section of leukemic proliferation in the formations of the CNS, including the brain stem, there were no changes.

0 in the membranes and substance of the brain, characteristic of cellular infiltration of the type of impregnation.

Thus, this example clearly illustrates the significant differences and high diagnostic efficacy of the method compared with the known diagnostic method (prototype). These pathologic studies confirmed the diagnosis established by this method, while the absence of leukemic proliferation in the The CNS, including in the brain stem, as was incorrectly diagnosed by a known method, confirms the impossibility of its use for the purpose of differential diagnosis. sticks of various types and variants of cellular infiltration of the nervous system in patients with leukemia.

0 Over the diagnostic method of diagnosis

patient with acute lymphoblastic leukemia

The following clinical and liquor diagnostic criteria were identified:

clinical neurological symptoms that affect the membranes and substances of the brain in the form of right-sided facio-lingo-brachial syndrome, diffuse organic symptomatology, liquorodynamic disorders and crises

0 sympathoadrenal and vaginal insulin;

 liquorological indicators - xantochrome and CSF and red blood cells, which in the last portion are much more than

5 first;

remitting flow, and with correction of the hemostasis system and detoxification - regressing;

clinical and liquor data

0 revealed in dynamics confirm the accuracy of the diagnosis established by the method;

the pattern of clinical-liquorologic relationships is the dissociation between

5 symptoms of multifocal lesion of the membranes and brain substance in the form of the facio-lingo-brachial syndrome, liquorodynamic disorders and crises of the sympathoadrenal and vaginal insulin nature and unexpressed pleocytosis

, 533 10 cells / l) against the background of erythrocytes and xangochromia CSF. The diagnosis of cellular, including goat, leukemic, infiltration by the claimed method is reliable in 100% of patients (in the prototype, it is unreliable in 100% of patients).

Example. Patient M., 16 years old.

Diagnosis: Acute lymphoblastic leukemia, deployed step, remission, leukemic infiltration with CNS combined type formations, the dispersed organic light symptomatology, bilateral pyramidal deficiency and insufficiency group caudal nerve moderate likvorodina- ical disorders and mild as- Teno-vegetative syndrome.

Anamnesis. Complaints of severity in the head, increasing during the month, with bouts of severe headache, two days ago with a single vomiting. Body temperature is not measured l. Neurological examination: a study of craniocerebral innervation revealed luga bilateral insufficiency of the caudal group of cranial nerves, mild bilateral pyramidal insufficiency was easy; blood pressure asymmetry: S 110/80, d 100/70. Reduced adaptation stock. The pronounced istozem of sharpness with a load of up to 15 cm / min. Body temperature 36.9 °.

Preliminary clinical diagnosis. Immediate correction of the hemostatic system was performed, detoxification and antiretroviral therapy, after which the patient's general condition improved, headache attacks disappeared, headache decreased, blood pressure became symmetrical (110/70), adaptation stock increased, exhaustion decreased (sharpness Occupied with a load of 7 cm / min). However, the root and pyramid deficiency are unchanged,

Liquorodiagnostics Liquor pressure is 1940 hPa, 3 ml of liquor is extracted under mandrin in five test tubes, the liquor is transparent, xanthochromic. Microscopic - pleocytosis in both portions of 192-106 cells / l, morphology - blasts, single monocytes, macrophages, erythrophages on the background of red blood cells, which are more in the last portion. Liquorological data confirm the established clinical diagnosis.

After treatment: correction of the hemostasis system, detoxification, decongestants, analgesics, followed by endolumbus administration of methotrexate at a dose of 8 mg / m2 at intervals of seven days, five

of injections, a full regression of symptoms occurred after 0.25 months, followed by remission.

When controlling liquor diagnosis:

The CSF cytosis of 06.06.1985 was 2-U6, 07.26.1985 - 1-U6 and 08/23/1985 20-106 cells / l, remission according to the clinical-liquorologic indicators lasted for 10 months ., until the end of the patient's life,

the cause of death is intoxication.

Thus, the following diagnostic criteria for leukemic infiltration of NS of the combined type, caused by the processes of proliferation and impregnation of leukemic cells in the formation of the central nervous system, were identified in a patient with acute lymphoblastic leukemia according to the method.

clinical neurological indicators: bilateral pyramidal insufficiency, symmetrical failure of the caudal group of cranial nerves against the background of scattered multifocal symptoms;

liquorological indicators - blasts

against the background of erythrophages, xanthochromia and erythrocytes, which are more in the last portion;

progressive remitting course and regressing with treatment adequate to the diagnosis established above;

Clinico-liquor-logical data, revealed in dynamics, confirm the accuracy of the diagnosis established by the method;

The pattern of clinical-liquorological correlations: symptoms of symmetrical lesions of formations mainly on the basis of the brain in the form of attacks of a sharp headache against the background of their gradual development, bilateral pyramidal and radicular insufficiency and scattered organic symptomatology correspond to leukemic pleocytosis (192-10 cells / l) against the background of erythrophages, erythrocytes and xanthochromia of the cerebrospinal fluid with a progressively-relapsing course.

The diagnosis of leukemic infiltration of the combined type according to the inventive method is reliable in 100% of patients (in the prototype it is unreliable in 100% of patients).

In the diagnosis of NA lesions in patients with leukemia using the proposed method, the regression of clinical neurological manifestations in 100% of patients averages

for 0.32 ± C, 06 months (in the prototype of the regression of symptoms was not 100% of patients);

73% of patients did not have a relapse, 22% of patients had one relapse and 2 relapses 2 relapses each (in the prototype all

100% of patients were noted continuously progressive course);

The duration of remission according to the clinical and clinical indicators is on average 13 ± 7.2 months. (in the prototype there was no remission in 100% of patients);

life expectancy from the start of diagnosis is on average 18 ± 7.4 months. (in the prototype, on average, 1.4 ± 0.9 months at t 2.26);

average increase in life expectancy of 16 ± 6.5 months;

cure was noted in 89.9% of patients (in the prototype there was no cure in 100% of patients);

Diagnostics of various types and variants of cell infiltration of NS formations during verification is reliable in all 100% of patients (in the prototype, they are not differentiated in 100% of patients, since the diagnostics is based on detection of only blasts in the liquor).

The claimed method is highly informative and can be recommended for diagnosing HC lesions in any diseases, it does not require the use of special expensive equipment and can be applied not only in inpatient but also in outpatient settings.

Claims (7)

1. A method for diagnosing damage to the nervous system in leukemia, which includes detection of power cells in the cerebrospinal fluid, characterized in that, in order to reduce mortality, increase longevity and remission, the presence of headaches and increase in body temperature are detected when detecting types of damage to the nervous system. , the time of appearance and development of symptoms - symmetrical or asymmetrical, diffuse, focal or combined damage of the vascular-epithelial plexus, membranes and head substance and spinal cord, roots or terminal branches of nerves, visual-changing color of the CSF, microscopically - cytosis, pleocytosis, cell morphology, immunoblasts, polyblasts, erythrophages, pigment phages, erythrocyte count in the first and last portion of the liquor, are detected, progressive, regressive-remitting or progressive-remitting pathology, the dynamics of these parameters before and after treatment and diagnose the type of lesion of the nervous system in leukemia. 2. A method according to claim 1, characterized in that during dissociation between unexpressed symptoms of symmetrical lesions of formations, mainly on the basis of the brain, in the form of pyramidal insufficiency and radicular syndrome III, Y-XII pairs of cranial nerves, with a gradual development of 1.5 ± 0.5 months., Against the background of normal body temperature, and pronounced leukemia- (4022 ± 5428) -106kl. / l pleocytosis, progressive course and regressing - with the suppression of leukemia process - leukemia infiltration of a proliferative type is diagnosed. 3. The method according to claim 1, characterized in that during dissociation between the expressed symptoms of asymmetric damage to the nerve roots against the background of high body temperature with subacute development, 0.3 ± 0.2 months. and unexpressed macrophage-lymphoid (17 ± 11) -106 cells / l pleocytosis and regressive course in anti-infective therapy - cell proliferation of a proliferative type from cells of the macrophage and immunocompetent systems is diagnosed under the influence of infectious progress. 4. A method according to claim 1, characterized in that when symptoms of a diffuse lesion of the nervous system are predominantly in the form of hypothalamic and polyneuropathic syndromes with acute-subacute development and macrophage (82 ± 52) -106 cells / l pleocytosis, with progressive over and regressive - with detoxification therapy - diagnose cell infiltration of proliferative type from cells of the macrophage and immunocompetent systems, under the influence of the toxic process. 5. The method according to claim 1, characterized in that when irritation symptoms of the morphological substrate of the immune barrier of the brain are present in the form of meningeal syndrome with acute subacute development and lymphoid - (590 ± 250) -10 cells / l pleocytosis with a regressing course - it is diagnosed cell infiltration of the proliferative type from cells of the immunocompetent system under the influence of the immune process. 6. The method according to claim 1, characterized in that when symptoms of diffuse damage occur in the perivascular spaces of the nervous system in the form of cerebral and radicular syndromes and symptoms that mimic the root syndrome, edema caused by structures not related to the formation of the nervous system, and pleocytosis (199 ± 107) -10 cells / l from unidentifiable and immunocompetent cells over the course of the process depending on paradoxical or ultra paradoxical CNS phases - diagnose cell infiltration of a proliferative type from unidentifiable and immunocompetent cells. 7. A method according to claim 1, characterized in that during dissociation between the symptoms of a focal or multifocal lesion of the nervous system, mainly the soft sheath and brain substance in the form of facio-lingvo-brachial, convulsive, etc. syndromes with acute development - 0.05 ± 0.02 months. and unexpressed leukemia - (65 ± 140) -106 cells / l by pleocytosis or from other blood cells on the background of erythrocytes, erythrophages, pigment-phages or xanthochromies with a remitting course — they diagnose cellular, including leukemic, infiltration of impregnation type. Editor Tehred M. Morgenthal Order 3383 Circulation Subscription VNIIPI State Committee for Inventions and Discoveries at the State Committee on Science and Technology of the USSR 113035, Moscow, Zh-35, 4/5 Raushsk nab. Production and Publishing Combine Patent, Uzhgorod, Gagarin st., 101 Proofreader L. Fil