TUBERCULOUS
MENINGITIS: СLINICAL
MANIFESTATIONS, MODERN METHODS OF DIAGNOSIS AND THERAPY
Zhavoronkova
Yu.A., Shevchenko P.P., Karpov S.M.
The Stavropol State Medical University
Department of Neurology, Neurosurgery and Medical
Genetics.
Stavropol, Russia
Relevance. Nowadays
the problem of diagnostics and treatment of the tuberculous meningitis (TM)
cannot be considered to be solved even with the increased arsenal of diagnostic
and medical opportunities. The disease belongs to acutely progressing forms of
tuberculosis and it’s mortality rate is from 15 to 32,3% [1]. This fact
confirms the social importance of disease. Recently tubercular meningitis
occurs in 7 — 9% [6] cases out of total
number of TB patients. It can be the only localization of tubercular process,
but more often (70 — 80% of cases) [6] develops at the various forms of
pulmonary and extra pulmonary tuberculosis in different phases of its
development and can proceed irrespective of the main process in other organs.
The problem of tubercular meningitis
is a problem of late diagnostics and untimely appointed therapy that results in
unfavorable outcomes like invalidity or death of patients.
Objective: to analyze specificity of the
clinic, modern methods of diagnostics and treatment of tubercular meningitis
based on researches, monographs, tutorials.
Results. Tuberculosis
of the central nervous system and meninx of the brain is an infectious disease
caused by Mycobacterium tuberculosis which occurs primarily or secondarily with
formation of specific inflammation in affected areas and changes of
cerebrospinal fluid of serous character.
Tubercular encephalomeningitis is found in 70% of cases; tubercular
meningitis - in 26% of cases; 4% make forms which are seldom found:
meningoencefalomyelitis, tuberkuloma of
the brain, and also atypical forms of encephalomeningitis [3]. According to the
data of Research Institute of Phthisiatry of the First Moscow Medical
University named after I.M. Sechenov, TM mobidity in Russia made 0,05 — 0,02
per 100 000 of population [3]. Diagnosis of tuberculosis of meninges and
lesions of the central nervous system often appears unobvious at the initial
stage of the disease and is defined only during the manifestation of clinical
symptoms.
Tubercular meningitis is usually
defined by three groups of clinical signs:
1. The Meningeal syndrome includes a headache and contractures,
increased tone of the nape muscles, torso, abdomen (rigidity of occipital
muscles, the pulled-in stomach, an opisthotonus, Kernia’s sign, Brudzinsky's sign).
The Meningeal syndrome can be followed by vomiting, temperature increase,
dissociation of pulse and temperature, vasomotorial frustration (Trusso's
spots, red dermografizm), hyperestezia; emergence of pathological tendinous
reflexes (Babinsky, etc.) [7].
2. Symptoms of damage of
craniocerebral nerves and spinal membranes.
In tubercular meningitis all 12 pairs of craniocerebral nerves can
be damaged, more often the following ones:
3–d pair (nervus oculomotorius) - ptosis, miosis, mydriasis, the divergent squint.
6-th сouple (nervus
abducens)
- unilateral or bilateral convergent squint;
7-th couple (nervus facialis) - asymmetry of the face: on the part of defeat smoothing of nasolabial
fold, omission of a corner of a mouth, expansion of an eye crevice;
8-th couple (nervus vestibulocochlearis) - malfunction of a cochlear branch: feeling of noise, more often in the
form of a hypoacousis, rarely acouzia, vestibular disorders - dizziness,
feeling of falling, unsteady gait;
9 -th couple (nervus glossopharyngeus) - a dysphagia;
10 -th couple (nervus vagus) - an aphonia, frustration of rhythm of breath and pulse;
12 -th couple (nervus hypoglossus )- sublingual nerve
Change of ocular fundus is seen more
often in the form of stagnant nipples of optic nerves. Complaints of feeling of
an illegibility (fog) before eyes, when progressing – amblyopia up to
amaurosis. The trigeminal nerve is affected rarely [4,5].
3.
Syndrome of focal defeat of substance of the brain.
It is
manifested by aphasia, hemiplegia and a hemiparesis of the central origin [4].
According
to localization there are main forms of tubercular meningitis:
a)
basilar meningitis which is localized mainly on soft brain meninges at the base
of the brain;
b)
encephalomeningitis affecting the brain and its meninges;
c) the
spinal meningitis which is localized on soft covers of a spinal cord [2].
There are
3 periods in the clinic of tubercular meningitis: 1) prodromal,
2) the
period of irritations, 3) terminal (paresis and paralyzes)
1. The
Prodromal period is characterized by gradual (during 1-8 weeks) development. At
first there is a headache, dizziness, nausea, sometimes vomiting, fever. The
delay of urine and stool, subfebrile temperature is observed, more rarely there is a high temperature. However, there are
cases of the disease and at normal temperature [2].
2.
Irritation period: in 8-14 days after the
prodroma a sharp strengthening of symptoms occurs, the body temperature
is 38-39 °C, pain in frontal and occipital area of the head is felt.
Drowsiness, slackness, oppression of consciousness increases. Constipation without
swelling - scaphoid abdomen. Photophobia, hypersensitivity of the skin,
intolerance to noise. Vegetative-vascular disorders: resistant red
dermographism: spontaneously appear and disappear quickly red spots on the skin
of the face and chest. At the end of
the first week of the period of irritation (on the 5-7th day) the indistinctly
expressed meningeal syndrome occurs. Characteristic manifestations of symptoms
appear in the second period of irritation depending on localization of
inflammatory tubercular process. In inflammation of meningeal membranes headaches, nausea and stiff neck
are observed. With the accumulation of serous fluid at the base of the brain
the irritation of the cranial nerves can occur with the following signs:
amblyopia, paralysis of the eyelid, strabismus, anisocoria, deafness. Hypostasis of a nipple of an
eye bottom is observed in 40% of patients. Involvement of brain arteries in
pathological process can lead to the loss of speech or paresis. At hydrocephaly
of various degree of expressiveness there is a blocking by exudate of some
cerebrospinal connections with the brain. Hydrocephaly is the main reason of
loss of consciousness. At blockade of a spinal cord by exudate the weakness of
motor neurons or paralysis of the lower extremities can arise [2].
3. Terminal period (period of
paresis and paralyzes, the 15-24th day of illness). Predominant symptoms of
encephalitis: the absence of consciousness, tachycardia, Cheyn-Stokes's breathing,
body temperature is 40 °C, paresis, paralyzes of the central character. At a
spinal form in the 2nd and 3rd periods the surrounding, very severe radicular
pains, sluggish paralyzes, bedsores are observed. Diagnosis is: timely — within 10 days from the beginning
of the period of irritation; later —
after 15 days [2].
At making the diagnosis of
meningitis it is necessary to consider the following data: anamnesis (data of contact with TB patient),
the character of tuberculous tests (because of the severity of process it can
be negative, an anergy), existence and terms of vaccination (revaccination),
its effectiveness.
Clinical examination: a) character
of the beginning of a disease; b) character of the course of a disease; c)
condition of consciousness; d) expressiveness of meningeal symptoms; e) spinal
puncture, liquor, research of an eye bottom.
X-ray-tomographic research of a
thorax (lack of radiological changes does not exclude a tubercular etiology of
a disease).
KT and MRT of the brain due to which the expansion of
brain ventricles can be revealed.
Research of cerebrospinal fluid.
- Pressure of a column of liquor can
be determined approximately on liquid flow speed. Hypertension liquor stream flows or very frequent drops (20 drops per
minute), low pressure - drop rare).
- At tubercular meningitis liquor, as a rule, is transparent or
opalescent.
- Research of films: in 12-24 hours
a thin transparent fibrous grid is formed on the surface (like "the turned
fir-tree", a funnel).
- Cellular liquor structure: the
quantity of cells in liquor increases to 100-300 and more. Pleocytosis in the early stage of the disease can be neutrophilic,
lymphocytic (mixed), later on lymphocytic (to 100%). Liquor is investigated
also by a sowings method on MBT
and a nonspecific flora. Micobacteria of tuberculosis in liquor in tubercular
meningitis are seldom found.
- Protein content increased to
0,8-1,5 g/l and more {N 0,15-0,33gl) mainly due to globulins that is confirmed
by reactions of Pandi and Nonna-Appelta. The degree of opacity is evaluated to four-point scale (++++).
- Liquor is characterized by
decrease in content of sugar (N of 2,5-3,5 mmol/l) and chlorides (N of 120-530
mmol/l)..
- Cerebrospinal fluid is
investigated on MBT by bacterioscopy method and PTsR (polimerazno-chain
reaction).
- In encephalomeningitis and in a
spinal form of tubercular meningitis an increased amount of protein (to 4-5
g/l) is found in comparison with a basilar form of meningitis, and small
pleocytosis of lymphocytic nature (proteinaceous and cellular dissociation)
that reflects prevalence of stagnation
process over inflammatory. At the same time liquid is of xantochrom color.
Typically expressed decrease in content of sugar (up to 0) and chlorides is
evident in a liquor. Occlusion develops
in this period due to the large number of fibrin adhesion [4].
Patients with tubercular meningitis
should follow bed regimen for the first 1,5-2 months up to a distinct tendency
to normalization of liquor content. Then they are allowed to sit in bed while
having meals, and in 3 months – to walk in wards. They should have easily
digestible food rich in vitamins, proteins.
Obligatory examination of the
patient by ophthalmologist and neurologist is necessary in the first days of
the disease. Further survey by these experts should be done at least once every
3 months.
Therapy of the patient must be,
first of all, etiotropic and corresponds to the basic principles of treatment
of TB patients: timely, long and continuous, combined, complex, successive. Patients
dispensary monitoring is carried out in IA group till 1,5 – 2 years old.
Etiotropic therapy of the sick with
tubercular meningitis is provided in the conditions of a hospital. The
chemotherapy is carried out by a combination of 4-5 antitubercular preparations.
At the stage of an intensive phase of chemotherapy it includes: intravenous
drop therapy by 10% isoniazid solution, rifampicin and streptomycin
intramuscularly, ethambutol, pyrazinamide orally, in the absence of swallowing
– through a probe. 5% solution of saluyzid is administered endolumberly at the
rate of 5 mg/kg of the body weight. With positive clinical dynamics after 1-1.5
months of treatment it is possible to transfer it to the intermittent mode,
i.e. every other day (3 times a week). Duration of an intensive phase of
chemotherapy is defined individually by the solution of KEK, but it should not
be less than 3 months. The proceeding phase of chemotherapy is carried out by
2-3 antitubercular preparations (isoniazid, rifampicin, etambutol or
pyrazinamide). Duration of chemotherapy is defined by clinic-radiological and
laboratory data of SMZh, it can make 8-12 months.
In the presence of indications the
lumbar puncture is carried out in the first 2-3 weeks 2 times a week, then once
a week, then once every two weeks, once a month (till full sanitation of
liquor).
Pathogenetic therapy.
It includes: glucocorticosteroids
and potassium preparations (pananginum, asparkam).
Dehydrational therapy. In severe
cases of hypostasis of the brain and increasing hydrocephalus some osmotic diuretics are applied: manit,
furosemide (lasics), diacarb. For improvement of rheology and with the purpose
of desintoxication reopoliglyukin and a haemodes is administered, but with
obligatory account of urine.
Symptomatic therapy:
Anticonvulsive (реланиум, дроперидол, седуксен, GOMK).
Vascular therapy: (cavinton,
trental, piracetam (nootropil).
Resorbable therapy: subcutanious injections of vitreous body or fibs. In is necessary to begin resorbable
therapy after 3-4 months of etiotropic therapy.
During regression of inflammatory
changes cerebrolysin is appointed
Rehabilitation actions: remedial
gymnastics, massage after 4-5 months of treatment (at sanitation of a liquor).
Surgical treatment consists of
shunting operations on a hydrocephaly.
Conclusions: The perculiarity
of a clinical picture of tubercular meningitis is a few symptomatic
manifestations. The main way of diagnostics is a research of cerebrospinal
fluid. The key directions of therapy of tubercular meningitis are etiotropic
treatment with application of the main antitubercular preparations and a
symptomatic treatment. With early diagnosis and adequate treatment of
tubercular meningitis the positive result comes in 90% of patients while with
late diagnosis the development of complications begins (after the 18-th day) in
the most cases, up to a fatall outcome.
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