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“ЗАТВЕРДЖЕНО”
на методичній нараді кафедри
нервових хвороб, психіатрії
та медичної психології
“______” _______________ 2008 р.
Протокол № _____
Зав. кафедри нервових хвороб, психіатрії
та медичної психології
професор
В.М. Пашковський
.
METHODOLOGICAL INSTRUCTION № 24
THEME: Меningitis. Arachnoiditis.
Modul 2. Special neurology
Сontents modul 3. Infectious, infectious-allergic, demyelinating, parasitical diseases of
nervous system. Pryon infections, neuroborreliosis. Amyotrophic lateral sclerosis.
Subject:
Nervous deseases
Year 4
Medical faculty
Hours 2
Author of methodological instructions
MD Filipets O.O.
Chernivtsy 2008
1. Scientific and methodological substantiation of the theme.
Microorganisms may gain access to the ventriculo-subarachnoid space by way
of the blood stream in the course of a septicemia or as a metastasis from infection of
the heart, lung and other viscera.
Infectious diseases of CNS are met in all medical specialties, especially in
emergency, because neiroinfection course is severe and sometimes demand urgent
help. Treatment in time determines result of diseases. All specialists must know
diagnostic principles of infectious diseases of CNS.
2. Aim: To study etiology and pathogenesis of meningitis, clinical
characteristics and main neurological signs of different forms of meningitis, which
are necessary to make a correct diagnosis and to administer emergency treatment. To
be able to diagnose independently different forms of meningitis in patients, to
prescribe treatment, develop prophylactic measures, to provide capacity examination
in this category of patients.
Students must know:
1. Classification of meningitis.
2. Etiology and pathogenesis of meningitis.
3. Etiology and pathogenesis of arachnoiditis.
4. Clinical signs of meningitis.
1.
2.
3.
4.
1.
2.
3.
4.
5.
Students should be able to:
Examine the patient with meningitis.
Make a correct topical diagnosis.
Make a correct clinical diagnosis.
Prescribe the treatment.
Student should gain practical skills:
To carry out examinations of somatic and neurologic state.
To carry out examinations of meningeal signs.
Estimate additional methods of examination: laboratory, roentgenologic,
radiopaque methods.
To interpret the pathogenetic mechanisms of meningitis.
To employ the methods of pathogenic and symptomatic therapy
(pharmacology).
4. Integration (basic level).
Subjects
Anatomy
Gained skills
Knowledge of structure of subarachnoide space,
the arachnoid and and pia of brain and spinal
cord.
Histology
Physiology
Hystological structure of subarachnoide space,
the arachnoid and and pia of brain and spinal
cord
Knowledge of function of cerebrospinal fluid,
characteristics of normal liquor.
The law of polarization of biological membranes.
Subject
Involvement of the meninges by pathogenic microorganisms is known as
leptomeningitis. These cases are subdivided into two groups, acute and subacute
meningitis according to the severity of the inflammatory reactions, which in part is
related to the nature of the infecting organism.
Classification
I. A) primary meningitis (meningicoccal, choriomeningitis)
B) secondary meningitis (pneumococcal staphylococcal, tuberculous, EKHO,
Coxsakic and other).
II. A) Pyogenic meningitis (bacterial)
B) Serous meningitis (all viral, tuberculous, syphilitic)
C) Hemorrhagel meningitis (influenzal)
III.
A) Convexital meningitis;
B) Basal meningitis.
IV. Brick-light; Acute; Subacute; Chronic
V. Light; Middle; Difficult.
VI. Bacterial (meningococcal, pneumococcal,
tuberculoses)
Viral (enteroviral, herpes-simplex, herpes-zoster)
Fungal
staphylococcal,
streptococcal,
Acute Pyogenic Meningitis
Microorganisms may gain access to the ventriculo-subarachnoid space by way
of the blood stream in the course of a septicemia or as a metastasis from infection of
the heart, lung and other viscera.
The meninges may be invaded by direct extension from a septic focus in the skull,
spine or parenchyma of the nervous system.
Organisms may gain entrance to the subarachnoid space through compound
fractures of the skull and fractures through the nasal sinuses or mastoid.
They may be introduced by lumbar puncture performed for the removal of fluid
or the injection of sera, air, contrast media, anesthetics and the like.
Neonatal meningitis is frequently due to genitourinary infections in the mother.
The pathology, symptomatology and clinical course of patients with acute purulent
meningitis are similar regardless of the causative organisms. The diagnosis and
program of therapy depend on the isolation and identification of the organise, and
the determination of the source of the infection.
Pathogenesis. Acute purulent meningitis may be the result of infection with
almost any of the pathogenic bacteria. Isolated examples of infection by the
uncommon forms are recorded in the literature, but most frequently the
meningococcus, pneumococcus, streptococcus are the causative organisms.
Staphylococcus and coliform are gram-negative bacteria. In infants and young
children Hemophilus influenzae is the cause of purulent meningitis in approximately
one third of the patients. In the neonatal period E. coli, Group B streptococci,
Staphylococcus aureus and Listeria monocytogenes are the most common causative
agents.
Meningococcal Meningitis.
Meningococcal meningitis or acute cerebrospinal fever was described by
Vieusseux in 1805 and the causative organism was identified by Weichselbaum in
1887. It. occurs almost constantly in sporadic form and at irregular intervals in
epidemic form.
Pathogenesis. The meningococci (Neisseria meningitidis) may gain access to
the meninges directly from the nasopharynx through the cribriform plate or by way
of the blood stream. The fact that organisms can be cultured from the blood or from
cutaneous lesjons before the appearance of meningitis is strong evidence that the
infection takes place through the blood stream by way of the chorioid plexus in many
it not all, cases. In addition, it has been shown that the ventricular fluid may be
teeming with organisms before infection of the meninges is evident.
Pathology. In acute fulminating cases death may occur before there are any
significant pathological changes in the nervous system. In the usual case where
death does not occur for several days after the onset of the disease, there is an intense
inflammatory reaction in the meninges. The inflammatory reaction is especially
severe in the subarachnoid spaces over the convexity of the brain and around the
cisterns at the base of the brain and it may extend a short distance along the
perivascular spaces into the substance of the brain and spinal cord.
Rarely the inflammatory reaction, breaks into the parenchyma. Meningococci,
both intra- and extracellularly, are found in the meninges and the fluid from the
vetricles and subarachnoid space.
With progress of the infection the pia-arachnoid becomes thickened and
adhesions may form. Adhesions at the base may interfere with the flow of
cerebrospinal fluid from the fourth ventricle and produce hydrocephalus.
Inflammatory reaction and fibrosis of the meninges along the roots of the cranial
nerves are thought to be the cause of the cranial nerve palsies which occasionally
develop. This is not the only mechanism for such paralyses, however. Damage to the
auditory nerve often occurs suddenly, and the auditory defect is usually permanent.
This may be explained as the result of extension of the infection to the inner ear or to
thrombosis of the nutrient artery.
In addition, facial paralysis not infrequently occurs after the meningeal reaction
has subsided and is best explained on another, perhaps allergic, basis. Signs and
symptoms of parenchymatous damage, hemiplegia, aphasia, or cerebellar signs
are infrequent and are probably due to the formation of infarcts as the result of
thrombosis of inflamed arteries or veins.
Damage to the spinal cord, myelitis, is explained on a similar basis. Myelitis or
damage to the roots of the cauda equina is rare in the absence of intrathecal
treatment with serum or chemicals and it is probable that the latter substances
play an important role in the production of these complications.
With efficient treatment, and in some cases without treatment, the inflammatory
reaction in the meninges subsides and no evidence of the infection may be found at
autopsy in patients who die some months or years later.
Incidence. The meningococcus is the causative organism in approximately one
fourth of all cases of purulent meningitis. While both the sporadic and epidemic
forms of the disease may attack individuals of all ages, children are predominantly
affected. In many large epidemics over 75% of the cases were under ten years of
age.
Males appear to be slightly more susceptible than females. The normal habi tat
of the meningococcus is the nasopharynx and the disease is spread by carriers or by
individuals with the disease. An effective polysaccharide vaccine for Groups A and
C meningococci is available. Its use has reduced the incidence of meningococcal
infection among military recruits.
Symptomatology. The onset of meningococcal meningitis, similar to that of
other forms of meningitis, is accompanied by chills and fever, headache, nausea and
vomiting, pain in the back, stiffness of the neck, and prostration.
The occurrence of herpes simplex, conjunctivitis and petechial or hemorrhagic
skin rash is common with meningococcal infections.
With progress of the disease, the sensorium becomes clouded and stupor or coma
may develop. Occasionally the onset may be accompanied by deep coma.
Convulsive seizures are not infrequently an early symptom, but focal
neurological signs are uncommon. Acute fulminating cases with severe circulatory
collapse are relatively rare.
Signs. The patient appears acutely ill, and may be confused, stuporous or
semicomatose. The temperature is elevated to 39 or 40° C, but occasionally it may
be normal at the onset. The pulse is usually rapid and the respiratory rate is
increased. Blood pressure is normal except in acute fulminating cases when there
may be a severe degree of hypotension. There is rigidity of the neck with positive
Kernig and Brudzinski signs. The reflexes are often decreased but occasionally
they may be increased. Cranial nerve palsies and focal neurological signs are
uncommon. These complications usually do not develop until several days after the
onset of the infection. The optic discs are normal, but choking may develop if the
meningitis persists for more than a week.
Laboratory Data. The white blood cells in the peripheral blood are increased with
counts usually in the range of 10v000 to 30,000 per cu mm, but they occasionally
may be within normal limits or higher than 40,000 per cu mm.
The urine may contain albumin, casts and red blood cells.
Meningococci can be cultured from the nasopharynx in practically all cases,
from the blood in over one half of the cases in the early stages, and from the skin
lesions when these are present.
The cerebrospinal fluid is under increased pressure, usually between 200 and 300
mm of water. The fluid is cloudy or purulent and contains a large number of
cells, predominantly polymorphonuclear leukocytes. The cell count in the fluid is
usually between 2,000 and 10,000 per cu mm. Occasionally it may be less than 100
and infrequently more-than 20,000 per cu mm. The protein content is increased.
The sugar content is decreased, usually to levels below 20mg per 100 m.
Organisms can be seen intra- and extracellularly in stained smears of the fluid
and they can be cultured on the appropriate nedia in over 90% of untreated Gases.
Counter-current immunoelectrophoresis may demonstrate Meningococcal antigen
in spinal fluid.
Complications and Sequelae. The complications and sequelae in-dude those
commonly associated with an inflammatory process in the meninges and its blood
vessels (convulsions, cranial nerve palsies, focal cerebral lesions, damage to the
spinal cord or nerve roots, hydrocephalus), and those which are due to involvement
of other; portions of the body by meningococci such as:
- panophthalmitis and other types of icular infection, arthritis,
- purpura, pericarditis,
- endocarditis, myocarditis,
- pleurisy,
- orchitis, epididymitis,
- albuminuria or hematuria, and adrenal hemorrhage.
- disseminated intravascular coagulation may complicate the meningitis.
In addition there may be complications arising as the result of intercurrent
infection of the upper respiratory tract, middle ear and lungs. Any of the above
complications may leave a permanent residual but the most common sequelae are
due to injury of the nervous system. These include deafness, ocular palsies,
blindness, changes in mentality, convulsions and hydrocephalus.
With the methods of treatment available at the present time, complications and
sequelae of the meningeal infection are rare and the complications due to the
involvement of other parts of the body by the meningococci or other intercurrent
infections are more readily controlled.
Sixth nerve palsy developed early in the course of the disease in 3% and
completely disappeared within a few weeks.
Seventh nerve palsy occurred as late complication in 3% of the cases. It usually
developed between the fifth and fourteenth day, at a time when the cerebrospinal
fluid was relatively cell-free.
Recovery from the facial paralysis, either unilateral or bilateral, was usually
complete within a few months.
Eighth nerve palsy, usually bilateral, was present in 2% and was folk wed by
permanent deafness.
Focal neurological signs—convulsions, hemiplegia and aphasia—were present
in only 1%, and in all of these the signs and symptoms were transient
Diagnosis. The diagnosis of meningococcal meningitis can be made with
certainly only by the isolation of the organism from the cerebrospinal fluid.
However, the diagnosis can be made with relative certainty before the organisms are
isolated in patient with headache, vomiting, chills and fever, stiffness of the neck,
and a petechial cutaneous rash, especially if there is an epidemic of meningococcal
meningitis or if there has been exposure to a known case of meningococcal
meningitis.
In establishing the diagnosis of meningococcal meningitis, cultures should be
made of the skin lesions, nasopharyngeal secretions, blood and cerebrospinal
fluid. Since meningococci are particularly sensitive to chilling and freezing it is
important that inoculation of the appropriate media is made promptly, preferably
directly from the lumbar puncture needle.
In addition, a tube containing 5 to 10 ml of fluid can be incubated for subculture
after few hours. The diagnosis can be established in *he majority of cases by
exaixlinati~ n of smears of the sediment of the cerebrospinal flu'd, which have been
stained by the Gram stain.
Prognosis. The mortality of untreated meningococcal meningitis varied widely in
different epidemics, but was usually between 50 arid 90%. There is little evidence to
indicate that the older forms of therapy, particularly that in which immune serum
was injected intravenously and intrathecally had any appreciable effect on the
course of the disease. With present-day therapy, however, the mortality rate is less
than 5% and the incidence of complications and sequel is low.
Features of the disease which influence the mortality rate are the age of the
patient, the presence of bacteremia, type of meningococcus, day of treatment,
complications, and general condition of the patient.
The lowest fatality rates are seen in patient between the ages of five and ten years,
and in patients without bacteremia who are treated early in the course of the disease.
The highest mortality rates occur in infants, in elderly, debilitated individuals, in
those who are treated late in the course of the disease and in those with extensive
hemorrhages into the adrenal gland.
Treatment;
Cure pyogenict meningitis
I.
Aetiological (antibiotics sulfanilamide).
Antibiotics:
- benzil-penicillin 24-32- 48 mln.U. per day (300 th. U. per weight kg)
for 7-10 days;
- half synthetic penicillin:(ampicillin, amoxicillin) -10-12g/kg on day
- preparations of cephalosporin row (III, IV generations) 1g 6-8 times per
day;
- aminoglicosids (gentamicin, amicacin 80 mg 2-3 times per day),
- tienamicins (tienam, mefoxin) 1-2 g per day;
- fthorhinolons (ciprobai 500 th.U. 2-3 times per day, zanocin 200 mg 2
times per day).
Sulfanilamids (sulfamonometoxin 2 g 2 times per day).
Aqueous penicillin G or ampicillin administered intravenously is the treatment of
choice. If the patient is allergic to penicillin, chloramphenicol is the preferred
alternative drug. The duration of treatment should be seven to ten days.
The cerebrospinal fluid should be examined twenty-four hours after the initiation
of treatment in order to assess the effectiveness of the treatment and reexamined
after the full course has been given.
The state of the fluid balance and hydration should be carefully monitored by.
the measurement of central venous pressure.
Dehydration is common i and fluids should be replaced by intravenous
administration. Hyponatremia, which is not uncommon, may be due to excessive
fluid intake or the inappropriate secretion of antidiuretic hormone. It can be relieved
by the restriction of water intake.
Increased intracranial pressure can usually be controlled by removal of
cerebrospinal fluid. The development of cerebral edema may require the use of
osmotic diuretics such as intravenous mannitol solution or the administration of
dexamethasone.
Diphenylhydantoin, diazepam, or phenobarbital can be used to control recurrent
convulsive seizures.
If hypovolemic shock occurs, volume expansion with isotonic electrolyte
solution is indicated. Isoproterenol or dopamine may be required. Heparinization
should be considered if there is evidence of intravascular clotting.
Persons who have had intimate contact with meningococcal meningiitis
should be given rifampin or monocycline for three to four days as preventive
measure.
Pneumococcal Meningitis
The pneumococcus (Streptococcus pneumoniae) is next in frequency to the
meningococcus and influenza bacillus as a cause of meningitis. Meningeal infection
is usually a complication of otitis media, mastoiditis, and sinusitis, fractures of the
skull, upper respiratory infections and infections of the lung.
Alcoholism, asplenism, sickle cell disease and multiple myeloma predispose
patients to developing pneumococcal meningitis.
The infection may occur at any age, but over 50% of the cases are less than one
or over fifty years of age. The two sexes are about equally involved.
The clinical symptoms, physical signs and laboratory findings in pneumococcal
meningitis are the same as those of other forms of acute purulent meningitis.
The diagnosis is usually made without difficulty because the cerebrospinal fluid
contains large numbers of the organisms. When gram-positive diplococci are seen
in smears of the fluid or its sediment, a positive Neufeld reaction will serve to
identify
both
the
pneumococcus
and
its
type.
Counter-current
immunoelectrophoresis of spinal fluid and serum may be helpful in demonstrating
pneumococcal antigen. When the meningitis is secondary to mastoid or nasal sinus
infection, the type III pneumococcus is most common; in postpneumonic infections
pneumococci of types I and II are most common; in meningitis following fracture of
the skull the organisms are usually of higher types and correspond to strains of lesser
virulence which are normally present in the nose and throat.
Prior to the introduction of sulfonamides the mortality rate in pneumococcal
meningitis was almost 100% and at the present time it is still in the neighborhood of
30 %.
The prognosis for recovery is best in cases which follow fractures of the skull and
those with no known source of infection. The mortality rate is especially high
when the meningitis follows pneumonia, empyema, lung abscess, or when there is a
persisting bacteremia indicating the presence of an endocarditis.
Aqueous benzyl penicillin or ampicillin given intravenously is the drug of
choice in the treatment of pneumococcal meningitis. The treatment should be
continued for twelve to fifteen days. The primary focus of infection should be
eradicated by surgery if necessary. Persistent cerebrospinal fluid fistulas following
fractures of the skull must be closed by craniotomy and suturing of the dura.
Otherwise the meningitis will almost certainly recur.
Staphylococcal Meningitis
The staphylococcus is a relatively infrequent cause of meningitis. Meningitis may
develop as a result of spread from furuncles on the face or from Staphylococcal
infections elsewhere in the body. It is not infrequently a complication of cavernous
sinus thrombosis, epidural or subdural abscess and neurosurgical procedures
involving shunting to relieve hydrocephalus.
Intravenous methicillin or nafcillin is the preferred treatment. Therapy must be
continued for two to four weeks.
Complications such as ventriculitis, arachnoiditis and hydrocephalus may occur.
The original focus of infection should be eradicated. Laminectomy should be
performed immediately when a spinal epidural abscess is present and cranial
subdural abscess should be drained through craniotomy openings.
Streptococcal Meningitis
Infection with the streptococcus accounts for approximately 6% of all cases of
meningitis. Streptococcal meningitis is usually caused by group A organisms.
The symptoms are not distinguished from other forms of meningitis.
Occasionally, members of other groups may be isolated from spinal fluid. It is
always secondary to some septic focus, most commonly in the mastoid or nasal
sinuses.
Treatment is the same as outlined for the treatment of pneumococcal meningitis
together with surgical eradication of the primary focus.
Influenza Meningitis
Infections of the meninges by Hemophilus influenza were reported as early as
1899. At the present time it is the third most common type of acute purulent
meningitis and accounts for 18% of all cases of Meningitis.
In infants and children influenza meningitis is usually primary. In adults it is more
commonly secondary to acute sinusitis, otitis media, fracture of the skull, and
associated with spinal fluid rhino rhea, agammaglobulinemia, diabetes mellitus or
alcoholism.
It is predominantly a disease of infancy and early childhood, over 50% of the
cases occurring within the first two years of life and 90% before the age of five.
The disease affects the two sexes equally and is more prevalent in the winter
months.
The pathology of influenza meningitis does not differ from that of other forms of
acute purulent meningitis, except in cases with protracted course where localized
pockets of infection in the meninges or cortex, internal hydrocephalus, degeneration
of cranial nerves and focal loss of cerebral substance secondary to thrombosis of
vessels may be found.
The symptoms and physical signs of influenza meningitis are similar to those of
other forms of acute bacterial meningitis. The disease usually lasts ten to twenty
days. Occasionally it may be fulminating, and not infrequently it is protracted and
extends over period of several weeks or months.
The cerebrospinal fluid, changes are similar to those described for the other
acute meningitides. The organisms can be cultured from the cerebrospinal fluid.
Complications and sequel are common in untreated cases due to the protracted
course of the disease. These include: Paralysis of extra ocular muscles, deafness,
blindness, hemiplegia, recurrent convulsions and mental deficiency.
The mortality rate in untreated cases in influenza meningitis in infants is over
90%. The prognosis is not so grave in adults in whom spontaneous recovery is
more frequent. Adequate treatment has reduced the mortality rate to less than 5%,
but sequel are not uncommon.
The diagnosis of influenza meningitis is based on the isolation of the organisms
from the cerebrospinal fluid and blood on Fildes' or Leven-thal's medium. The type
of organism can be determined by means of capsular swelling with specific rabbit
antiserum. Hemophilus influenza antigen may be demonstrated in spinal fluid by
counter-immunoelectrophoresis. Although there are six known types, the vast
majority of the infections in infants are due to type G.
The emergence of ampicillin resistant Hemophilus, influenza strains has made it
necessary to begin treatment with ampicillin and chloramphenicol given
intravenously by separate injections.
As soon as the antibiotic sensitivity of the recovered bacterium is known, one
of the two antibiotics should be stopped, and the other continued for ten to fourteen
days until the patient is veil, the spinal fluid cell count less than 50 per cu mm and
the spinal fluid glucose normal.
Persistent vomiting, bulging fontanels, convulsion, focal neurological signs and
persistent fever should lead to consideration of this complication. Prompt relief of
the symptoms usually follows evacuation of the effusion by tapping the subdural
space through the fontanelles. Persistent or secondary fever without worsening of
meningeal signs may be due to an extracranial focus of infection, such as a
contaminated urinary or venous catheter, or to drug administration.
Meningitis Due to Other Bacteria
Meningitis in the newborn infant is most often caused by coliform gramnegative bacilli, especially E. coli, group B haemolytic streptococci,
Staphylococcus aureus and Listeria monocytogenes. It often accompanies
septicaemia and may show none of the typical signs of meningitis in children and
adults. Instead, the infant shows irritability, lethargy, anorexia and bulging
fontanelles. Meningitis due to gram-negative enteric bacteria also occurs frequently
in immunosuppressed or chronically ill, hospitalized patients or persons with
penetrating head injuries, congenital defects or diabetes mellitus.
Gentamicin is the drug of choice in meningitis due to enterobacteria. Intrathecal,
as well as intramuscular or intravenous therapy may be necessary, while spinal fluid
cultures remain positive because of the drug's poor penetration into the spinal fluid.
Meningitis due to Listeria monocytogenes may occur in immunosuppressed
adults as well as in infants. A laboratory report of "diphtheroids" seen on Gram
stain or isolated in culture should suggest the possible presence of Listeria
monocytogenes. The treatment of choice for Listeria monocytogenes meningitis is
ampicillin or benzyl penicillin.
Gonococcal meningitis usually presents in patients with other accompanying
signs and symptoms of gonorrhea. It most often occurs in Pregnancy or during
menses.
Tuberculous Meningitis
Tuberculous meningitis differs from that caused by most of the other common
bacteria in that the course is more prolonged, the mortality rate is higher, the changes
in the cerebrospinal fluid are less severe, and the treatment is less effective.
Pathogenesis. Tuberculous meningitis is always secondary to tuberculosis
elsewhere in the body. The primary focus of infection is most commonly in the
lungs, but it may be in the lymph glands, bones, nasal sinuses, gastrointestinal tract
or any other organ in the body. The onset of meningeal symptoms may coincide
with signs of acute miliary dissemination or there may be clinical evidence of
activity in the primary focus, but not infrequently the meningitis is the only
manifestation of activity of the disease.
It has been claimed that the meningitis is practically always secondary to rupture
of a cerebral tubercle into the ventriculo-subarachnoid spaces. In a number of cases
the meningitis may be a manifestation of an acute miliary dissemination of the
disease from other viscera, suggesting that the meningitis is due to lodgement of
bacteria directly in the meninges or choroid plexus.
Pathology. The older literature contains many reports of diffuse or circumscribed
granulomatous involvement of the meninges by tuberculosis. This form of the
infection is distinctly rare and the appearance of the brains of the patients who have
died in the acute stages of tuberculous meningitis is not very different from that seen
in other forms of meningitis. The meninges on the surface of the brain and the spinal
cord are cloudy and thickened but the process is often most intense at the base of the
brain. In fatal cases which are kept alive for some weeks by inadequate therapy, this
process may be so intense that it forms a thick collar of fibrosis around the optic
nerves, cerebral peduncles and basilar surface of the pons and midbrain. The
ventricles are moderately dilated and the ependymal lining is covered with exudates
or appears roughened (granular ependymitis). Minute tubercles may be visible in the
meninges, choroid plexus or cerebral substances.
On microscopic examination the exudates in the thickened meninges is composed
chiefly of mononuclear cells, lymphocytes, plasma cells, macrophages and fibroblasts
with an occasional giant cell. The inflammatory process may extend for a short
distance into the cerebral substance where minute granulomas may also be found.
Proliferative changes are frequently seen in the inflamed vessels of the meninges
producing a panarteritis similar to the Heubner type seen in chronic syphilitic
meningitis. These arthritic changes may lead to thrombosis of the vessel and
formation of infarcts in the cerebral substance.
Incidence. Tuberculous meningitis was formerly the most common form of
meningitis except for that due to meningococcus. With the advent of effective
methods of therapy for tuberculosis, the incidence of meningitis due to this
organism has decreased, but meningitis still remains the most serious complication
and the most common cause of death in tuberculoses children. Although
tuberculoses meningitis may occur at any age, it is most common in childhood and
early adult life. Approximately one third of the cases develop before the age of ten
and over 85% occur before the age of forty. It is rare below the age of six months.
The incidence in the two sexes is approximately equal.
Symptoms. The onset is usually sub acute, with headache, vomiting, fever,
apathy and irritability as the most prominent symptoms. Stiffness of the neck and
vomiting become evident within a few days. Convulsive seizures are not uncommon
in the children during the first days of the disease. The headache becomes
progressively more severe and in infants there is bulging of the fontanelles. The pain
often results in a peculiarly shrill cry (meningeal cry). With progress of the disease
patients become stuporous or comatose. Blindness and signs of damage to other
cranial nerves may appear or there may be convulsive seizures or focal neurological
signs.
Physical Findings. The physical findings in the early stages are those associated
with meningeal infection, i.e., fever, irritability, stiffness of the neck and Kernig's
sign. The deep reflexes may be exaggerated or depressed. Signs of increased
intracranial pressure and. focal damage to the nervous system ere rarely present at
the onset. The initial irritability is gradually replaced by apathy and stupor.
Choking of the discs, cranial nerve palsies and focal neurotome signs are common
in the latter stages of the disease. Clinical evidence of tuberculosis elsewhere in the
body may or not be present
The temperature, which is only moderately elevated (37,1-37,3 C) in the early
stages, rises to high levels before death. The respiratory and pulse rates are
increased. In the terminal stages respirations become irregular and of the CheyneStokes type.
Diagnosis. The diagnosis of tuberculous meningitis can be established only by
culturing the organisms from the cerebrospinal fluid of by results of inoculation of
guinea pigs. The cerebrospinal fluid findings are, however, quite characteristic and a
presumptive diagnosis can be made when the typical abnormalities are present.
These include: An increased pressure; a slightly cloudy or ground-glass appearance
to the fluid with formation of a clot on standing; a moderate pleocytosis varying
from 25 to 500 cells per cu mm, with lymphocytes as the predominating cell type;
increased protein content; decreased sugar content with values in the range of 20 to
40 mg per 100 ml; a negative serological test for syphilis; and absence of growth
when the fluid is inoculated on routine culture media. While no one of the above
abnormalities is diagnostic, their occurrence in combination is almost
pathognomonic, and. is sufficient evidence to warrant intensive therapy until the
diagnosis can be confirmed by stained smears of the sediment or pellicle, by cuhare
of the fluid of by guinea pig inoculation.. Other diagnostic aids include a thorough
search for a primary focus including roentgenograms of the chest and tuberculin
skin test. The latter is of .value chiefly in infants or young children.
Coxsackie Viruses Meningitis
In 1948 Dalldorf and Sickles inoculated specimens obtained from patients with
suspected poliomyelitis into the brains of newborn mice and discovered the
Coxsackie viruses. Coxsackie viruses have the structural and biological features of
the picornavirus group.
When they involve the human nervous system, both group A and group B
Coxsackie viruses most frequently cause so-called aseptic meningitis.
Coxsackie viruses are also known to produce herpangina, pericarditis and
myocarditis and epidemic myalgia (Born-holm disease).
The symptoms and signs of meningeal involvement are similar to those which
follow infection with any of the other known viruses. The onset may be acute or
subacute with fever, headache, malaise, nausea and abdominal pain. Stiffness of the
neck and vomiting usually has their onset twenty-four to forty-eight hours after the
initial symptoms. There is a mild or moderate elevation of the body temperature.
Muscular paralysis, sensory disturbances or reflex changes are rare. Muscular
paralyses, when present, are mild and transient. Occasionally meningeal symptoms
occur in combination with myalgia, pleurodynia or herpangina.
The cerebrospinal fluid pressure is normal or slightly increased. There is a mild
or moderate pleocytosis in the fluid, ranging from 25 to 250 per cu mm with 10 to
50% polymorphonuclear cells. The protein content is normal or slightly increased and
the sugar content is normal.
Diagnosis of infection with Coxsackie virus can be established only by
recovery of the virus from the feces, throat washings or cerebrospinal fluid and by
demonstrating an increase in viral antibodies in the serum. Meningitis is due to one
of the Coxsackie viruses cannot: be distinguished from the other viral agents which
cause the so-called aseptic meningitis except by laboratory studies. It is
differentiated from meningitis due to pyogenic bacteria and yeast by the relatively
low cell count and the normal sugar content in the cerebrospinal fluid.
ECHO Viruses Meningitis
This group of picomaviruses were originally isolated in cell culture from the
feces of apparently normal persons. They were considered "orphans" because they
lacked a parent disease. The designation.
ECHO was derived from the first letters of the term Enteric Cytopathogenic
Human Orphans. Thirty-three serotypes are now recognized. Many strains cause
hemagglutination of human type 0 erythrocytes.
The ECHO viruses have now been shown to produce gastroenteritis, macular
exanthema and upper respiratory infections. When the nervous system is
infected, the syndrome of aseptic meningitis results. Types 4, 6 and 9 are
particularly common causes of viral meningitis.
The clinical picture of infection with the ECHO viruses is similar to that of
nonparalytic poliomyelitis. Children are more frequently, affected than adults. The
main features of the disease are fever, coryza, sore throat, vomiting and diarrhea. A
rubelliform rash is present in a number of the cases. Headache, stiffness of the neck,
lethargy, irritability and slight muscular weakness are the symptoms which indicate
involvement of the nervous system and suggest the possibility of acute anterior
poliomyelitis. The disease usually runs a benign course with subsidence of the
symptoms in one or two weeks.
Cerebellar ataxia has been reported in children as the result of ECHO virus
infection. The onset of ataxia is acute; the course is benign with remission of the
symptoms within a few weeks. Oculomotor nerve paralysis with pupillomotor fiber
sparing has been observed in conjunction with ECHO virus infection.
The spinal fluid pleocytosis may vary from several hundred to a thousand or
more cells per cu mm, but is usually less than 500 per cu mm. Early in the infection
there may be as many as 90% polymorphonuclear leukocytes; within forty-eight
hours, however, the response becomes completely mononuclear. The protein content
of the fluid is normal or slightly elevated. The sugar conten remains normal.
The ECHO viruses are commonly recovered from feces, throat swabs or
cerebrospinal fluid. Humeri or simian monkey kidney cells are used in virus
isolation. Virus typing is carried out by neutralization or hemagglutination-inhibition
tests. Neutralizing antibodies are present in the serum one week after the onset of
illness and persist for several months.
Treatment
Attached to all kinds of meningitis set:
1. etiologic (antibiotics, sulfanilamide, antiviral),
2. pathogenetic (desintoxication, diuretic, hormones, antigistamines, nootrops,
antiagregants),
3. symptomatic (cardiac, sedative, analgetics) treatment.
I. Etiologic
Treatment of serous viral meningitis:
gama-globulin 6 ml intramuscular for 5 days, RNA-for 30 once 6 mg per day,
degidratics (Sol. Furosemidi 1% -2-4ml, Sol. Maniti 100-200 ml) glucocorticoids
(Sol.Dexametasoni 4-8-16 mg), antigistamins (Sol. Dimedroli 1% l-2ml)
and analgetics (Sol. Analgini 50 %-2 ml,Sol. Tramadoli 5 % 2 ml)
Treatment of tuberculous meningitis :
isoniasids 15 mg per weight kg 1-3 times per day during 2-3 months, rifampicin 600
mg once a day during 2-3 months, pirasinamid 30 mg per weight kg 2 times per day.
Treatment of zoster meningitis : aciclovir, Zovirax, virolex i5-30 mg per weight kg
3 times per d2,y up.Jp 10 days
II. Pathogenetic (joint ,attached to all meningitis). III. Symptomatic (joint attached
to all meningitis).
Tests for self-assessment:
1. Classification of meningitis.
2. Differentiated signs of liquor changes at tuberculous meningitis.
3. Clinical liquor signs of primary and secondary purulent meningitis.
4. Which pharmacological antibiotic groups are used for treatment of meningitis?
5. Antibiotic therapy prescription criteria of purulent meningitis.
6. Characteristic of cerebrospinal fluid in patient with serous meningitis.
7. What are the early signs of tuberculous meningitis?
8. Name complications of meningitis.
9. Name sequels of meningitis.
Tests
1. What clinical symptoms are dominant in making the diagnosis of
meningitis
a) liqour-hypertension syndrome;
b) focal neurological symptoms;
c) syndrome of infection disease;
d) general brain symptoms;
e) signs of inflammation in liquor.
a)
b)
c)
d)
e)
a)
b)
c)
d)
e)
2. What kind of speech disorders appears in patient with tumor of the frontal lobe of the
dominant hemisphere
Motor aphasia;
Amnesic aphasia;
dysartria;
sensor aphasia;
aphonia.
3. What is the main method of diagnostics of cerebral arachnoiditis
electromyography;
contrast myelography;
transcranial ultrasonography;
rheoencephalography;
CT.
Real-life situations:
1.
2.
Check meningeal syndrome.
Characteristic of cerebrospinal fluid in patients with tuberculous meningitis
References:
1.
Basic Neurology. Second Edition. John Gilroy, M.D. Pergamon press. McGraw Hill
international editions, medical series. – 1990.
2.
Clinical examinations in neurology /Mayo clinic and Mayo foundation. – 4th edition. –
W.B.Saunders Company, Philadelphia, London, Toronto. – 1976.
3.
McKeough, D.Michael. The coloring review of neuroscience /D.Michael McKeough/ 2nd ed. – 1995.
4.
Neurology for the house officer. – 3th edition. – howard L.Weiner, MD and Lawrence P.
Levitt, MD, - Williams&Wilkins. – Baltimore. – London. – 1980.
5.
Neurology in lectures. Shkrobot S.I., Hara I.I. Ternopil. – 2008.
6.
Van Allen’s Pictorial Manual of Neurologic Tests. – Robert L. Rodnitzky. -3th edition. –
Year Book Medical Publishers, inc.Chicago London Boca Raton. - 1981.