Download Meningeal syndrome

MINISTRY OF HEALTH CARE OF UZBEKISTAN
CENTRE OF MEDICAL EDUCATION
Tashkent Medical Academy
Department of Infectious and Pediatric Infectious Diseases
Subject: Infectious diseases
THEME:Early and differential diagnosis of infectious disease occurs with
meningeal syndrome
Educational-methodical development for teachers and students of medical faculty
Tashkent - 2008
MINISTRY OF HEALTH OF THE REPUBLIC OF UZBEKISTAN
CENTER OF DEVELOPMENT OF MEDICAL EDUCATION
TASHKENT MEDICAL ACADEMY
"A F F I R M E D"
Pro-rector of educational work
Professor Teshaev O.R.
__________________________
«____»____________2012
Department of infectious and pediatric infectious diseases
Subject: Infectious diseases
THEME:Early and differential diagnosis of infectious disease occurs with
meningeal syndrome
Educational-methodical guideline for teachers and students of Treatment Faculty
"A F F I R M E D"
at a DNC meeting of Therapeutic Faculty
Protocol № ___from_________2012
Chairman of DNC, Professor
Karimov M.Sh.___________
TASHKENT
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THEME:Early and differential diagnosis of infectious disease occurs with
meningeal syndrome
1. Place of the training, equipping.
- The auditorium;
- Department of ABI;
- Box department;
- polyclinic department;
- Diagnostic department;
- the emergency ward;
- Laboratories (clinical, biochemical, bacteriological, immunological);
- Case patients with meningeal syndrome slaydoscope; TV-video, teaching - supervising
program, scripts of work’s methods in small groups, situational tasks. Guidelines for self study
to practical training by infectious diseases.
2. The duration of learning subjects
Number of hours - 5
3. The purpose of classes:
- To develop skills in an integrated approach to clinical diagnosis of infectious diseases
with meningeal syndrome, rational use of laboratory studies in primary care. Develop a sense of
responsibility for the diagnosis and deontological communication skills with patients with
meningeal syndrome. Education of a rational therapy for prehospital and hospital decision of
hozpitalization questions;
- To bring interest to the profession, stimulate the process of self-education, and develop
a sense of responsibility and compassion to the sick, at parsing the topics at the bedside of
individual patient, in laboratories and in the classroom,;
- To develop scientific mentality, stimulate creative approach to solving non-standard
clinical tasks and the ability to make independent decisions on examples of parsed thematic
topics. To develop logical reasoning and ability to express their thoughts in professional
language.
Objectives
The student should know:
- Differential diagnosis of meningeal syndrome in the most common infectious diseases;
- Early rational laboratory diagnosis of infectious diseases with meningeal syndrome;
- Preparation the diagnostic algorithm for finding the presence of meningitis and meningism
symptoms.
The student must be able to:
- To carry out a professional medical history and examination of the patient;
- To characterize the meningeal syndrome;
- To establish a preliminary diagnosis on the basis of early and differential diagnosis;
- To appoint a targeted survey;
- To interpret dates of laboratory and instrumental methods of examination;
- To own clinical decision-making logic (to form a definitive diagnosis, to assess the severity of
the patient's condition and prognosis);
- To diagnose condition emergency and to provide first medical aid in the prehospital stage;
- to decide whether to sending the patient for a consultation or hospitalization to the appropriate
hospital;
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- To carry out rehabilitation of convalescents with hemorrhagic syndrome.
As a result of training the student should learn practical skills:
Skills of 1st order
- Examination of the patient;
- To determine the meningeal syndromes and symptoms;
- To take blood for serology;
-To take a throat swab for bacteriological research;
- To take a swab from the nose to the bacteriological research.
Skills of 2nd order
- Interpretation of laboratory data;
- Provide the necessary assistance on the prehospital stage;
- Carry out the primary antiepidemic measures at the source.
4. Motivation
The high incidence of meningeal syndrome with infectious diseases have necessitated the
development of skills of differential diagnosis of meningeal syndrome in GP-physicians.
5.Interdisciplinary communication Teaching this topic is based on the knowledges of
students in biochemistry of metabolic disorders, microbiology, immunology, pathological
anatomy, pathological physiology, physiology of the hypothalamic-pituitary system. The
findings of the studies of knowledge will be used during the passage of medicine, surgery,
obstetrics, gynecology, hematology and other clinical disciplines.
6.The content of training
6.1.The theoretical part
Syndromal or etiological undifferentiated diagnosis of meningitis, set on base
combination of following clinical and pathogenetic syndromes: meningeal (shell), an infectious
disease syndromes, changes in cerebrospinal fluid.
Meningeal syndrome consists of cerebral and meningeal symptoms itself. Cerebral
symptoms are very intense, excruciating expander, diffuse headache, , vomiting, nausea, often
without prior, the patient does not bring relief in severe - psychomotor agitation, delusions,
hallucinations, convulsions, occasionally alternating with lethargy and impaired consciousness ¬
(stupor, sopor, coma). Meningeal symptoms can be divided into 4 groups.
1st group includes general hyperesthesia - sensitivity to stimuli of the senses - light
(photophobia), sound (hyperacusis), tactile.
2nd group of meningeal symptoms include muscle tonic tension. KERNIG’S SIGN
Elicitation: Flexing the patient’s hip 90 degrees then extending the patient’s knee causes pain.
BRUDZINSKI’S NECK SIGN Elicitation: Flexing the patient’s neck causes flexion of the
patient’s hips and knees. BRUDZINSKI’S medium (pressure on the pubis leads to the same
reaction) and BRUDZINSKI’S lower (maximum Crouching low over bent at the knee of one
leg to the abdomen accompanied by automatically bending the other leg at the knee and hip
joints). Stiff long back muscles leads to the fact that the patient is bent backwards and can not
bend to forward.
In severe meningitis, the patient has very characteristic pose: head thrown back, as the
body unbent, his legs are given the abdomen, stomach, newborns and infants revealed a
symptom Lessazha ("suspension") at which lifting the child by the armpits results in bending the
legs in hip and knee joints, tightening of the stomach and prolonged fixation in such composition
(in a healthy child's legs move freely). Tension and protrusion of the large fontanelle is a
manifestationtion of intracranial hypertension.
In identifying of meningeal symptoms tonic muscle tension must be differentiated from a
false rigidity of the muscles due to pain (myositis, radiculitis, etc.) which can simulate a neck
muscle tension. In these cases, it is crucial the methodically identify the correct symptom: a slow
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and smooth bending the head forward, without much effort by the physician, neck stiffness, is
not there, it appears with the rapid and intensive bending of the head as a result of the pain
reaction.
Third group of meningeal symptoms include painful reactive phenomena: tenderness in
the eyeballs, in places where the facial branches of the trigeminal nerve , in the places where the
large occipital nerve exit (Kehrer points) on the front wall of the external auditory canal
(symptom of Mendel); increasing headache and pain during percussion grimace zygomatic arch
(a symptom of spondylitis) and skull (symptom of Pulatov).
4th group of meningeal symptoms may include abdominal changes, periosteal and
tendon reflexes: the beginning of a revival, and then irregular decline.
In meningitis is often revealed signs of encephalitis or myelitis, diagnosis and assessment
of symptoms of encephalitis should be done with a neurologist. When meningitis
(meningoencephalitis) revealed a number of clinical syndromes and pathogenesis of symptoms
characteristic of infectious diseases: general intoxication, fever, rash, and enanthema,
lymphadenopathy, enlarged liver and spleen, changes in the functions of various organs and
systems. This allows you to have pre-hospital to make a differential diagnosis of meningitis from
non-communicable diseases with meningeal syndrome.
For confirming the diagnosis of meningitis is necessary to study the cerebrospinal fluid
(CSF). The indications for lumbar puncture is the appearance of meningeal symptoms, even if
they are mild. The normal CSF is clear and colorless during the lumbar puncture follows in the
patient lying at a pressure of 100 to 200 mm of water. of Art. (0,98-0,96 kPa), contains (2-10) •
106 / L lymphocytes, 0,23-0,33 g / L protein, chloride 120-130 mmol / l glucose from 0.42 to 0 ,
6 g / l (ie, not less than 50% of the level of serum).
Inflammatory changes in the CSF is crucial for the diagnosis of meningitis.
Determination of pleocytosis, cellular composition, protein level, the concentration of sugar and
chloride is the first step in the differential diagnosis of meningitis.
Meningismus - a condition characterized by the presence of meningeal and cerebral
symptoms but without inflammatory changes in liquor. When lumbar puncture fluid is
transparent and colorless, it follows under increased pressure to 300-400 mm of water. of Art.
(2,9-3,9 kPa), part of the jet, but the content of the cells, protein, sugar and chlorides are normal.
Clinical signs of meningism are not caused by inflammation of the meninges, and their toxic
irritation and increased intracranial pressure. Meningismus can occur in patients with influenza
and other acute respiratory infections, meningococcal nasopharyngitis, tonsillitis, typhoid and
other diseases (scheme 1).
The etiological interpretation of these diseases carried out by using clinical and
laboratory methods. Meningismus, like meningitis, occurs more common among children. It
usually occurs in the acute phase of illness and lasts usually no more than 1-3 days. After the
first spinal tap and letting the CSF pressure to normal condition of the patients improved rapidly,
and meningeal signs will soon disappear. However, the phenomenon must always be alert
meningism doctor, as they are often preceded by inflammation of the meninges, which can
develop within hours after discovery of meningism. If meningeal phenomena does not disappear,
but grow even more, it is necessary to make repeated diagnostic lumbar puncture.
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Acute bacterial meningitis: In adults with hematogenous infection usually a single type
of organism is found. The most common pathogenic organisms are S. Pneumoniae, N.
meningitides and H. influenza (particularly in chronic lung disease patients, splenectomized
patients and immunocompromized patients), accounting for 75% of all sporadic infections.
Listeria monocytogenes (chronic illness, malignancy, organ transplantation, AIDS or
immunosuppressive therapy), staphylococcus (brain abscess, trauma and neurosurgery), S.
agalactiae (elderly with underlying disease), Klebsiella, Proteus and Pseudomonas (LP, spinal
anesthesia and shunting for hydrocephalus) are accounting for the remainder. When infection
disseminates from the lungs, heart or extends from ears or sinuses more than one type of
bacterial flora may be observed. Fever, severe headache, neck stiffness (predominantly on
forward flexion unlike the multidirectional rigidity in extrapyramidal disorders or paratonia),
seizures (17% in community-acquired forms) and alteration of consciousness are early clinical
effects of acute bacterial meningitis. Stiffness can sometimes be mild or absent. Meningococcal
meningitis (most commonly serogroups A, B and C) should be suspected in extremely rapidly
evolving meningitis with stupor, delirium and when the onset is associated with petechial or
purpuric rash, ecchymosae or shock. Pneumococcal meningitis is often preceded by an infection
in the lungs, ears, sinuses, or heart valves and should be suspected in alcoholic, splenectomized
patients, elderly, sickle cell patients and basilar skull fracture. HIV infection, hematologic
neoplasm and metastatic disease, collagen disorders, immunosuppressive therapy are conditions,
which favor invasion by Enterobacteriaceae, Listeria, A. calcoaceticus and Pseudomonas. Focal
seizures and stroke can occur. Meningeal signs may be absent in half the patients with Listeria
infections and the CSF may show mild abnormalities. All febrile patients even those with lowgrade fever and those with only lethargy, headache, or confusion of sudden onset should be
subjected to LP. CSF opening pressure <250 mm H2O is likely to be viral meningitis while
values in bacterial meningitis range between 200-500 mm H2O. When ICHT is suspected
(decreased level of consciousness) a 22-gauge needle LP 30 to 60 min after 1g/kg i.v. mannitol
infusion in addition to hyperventilation can be performed. Pleocytosis is diagnostic with
leucocytes predominantly neutrophils (90%) ranging from 250 to 10,000/mm3. CSF glucose
content < 40 mg/dL (or glucose blood/CSF ratio < 0.4). Protein content is > 45 mg/dL (100-500
mg/dL) in 90% of the cases and CSF lactate is increased in bacterial and fungal meningitis (>35
mg/dL). Gram stain examination of CSF allows a rapid and accurate identification of the
causative bacterium (N. meningitides, S. pneumoniae and H. influenza) in about 80% of cases
(40% for Listeria) and has a specificity of >97%. CSF culture (sheep blood agar, chocolate agar
and broth) is positive in 75% of patients with acute bacterial meningitis but may take up to 48
hours for organism identification. Depending on the bacteria the latex agglutination test
sensitivity varies between 50-100% (high sensitivity for H. influenza (60-90%) but less sensitive
for N. meningitides, S. pneumoniae, S. agalactiae, E. coli) and may be most efficacious in those
patients who have received antibiotic therapy prior to lumbar puncture. Limulus lysate may be
useful in suspected case of gram-negative meningitis (endotoxin). A negative limulus test does
not rule out the diagnosis of gram-negative meningitis and therefore is not used routinely. PCR
has been utilized in meningitis caused by common meningeal pathogens, including N.
meningitides, S. pneumoniae, H. influenza type b, S. agalactiae and L. monocytogenes. The
diagnostic sensitivity and specificity are 94 and 96%, respectively. Patients with bacterial
meningitis should have a repeat LP 24 to 36 hours after to initiation of therapy to document
sterilization of the CSF.
Blood cultures should always be obtained because they are positive in 50% of the cases
with S. Pneumoniae, N. meningitides and H. influenza. Meningitis may be complicated within a
few days by hyponatremia due to SIADH. Brain MRI may be normal or show abnormal signals
in the brainstem (rhombencephalomeningitis) in Listeria infection. Recurrent bacterial
meningitis should suspect congenital neuroectodermal sinus or sinoidal fistula. Empiric
intravenous treatment (ceftriaxone 2 g q12h - with ampicillin 3 g q6h if listeria is suspected - and
plus vancomycin 1 g q12h with or without rifampicin in penicillin-resistant pneumococci, and
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acyclovir if herpes is suspected) should be started while awaiting the results of CSF and blood
cultures, and subsequently be adjusted, and should last at least 2 weeks. Prolongation of fever or
focal neurologic signs may indicate subdural effusion, mastoiditis, venous sinus thrombosis,
cortical vein phlebitis or brain abscess.
Meningo encephalitic syndrome may be caused by Mycoplasma pneumoniae,
Listeria monocytogenes, and legionnaires disease.
In peumococcal meningitis and all other acute bacterial meningites with moderate to
severe Glasgow coma scale on admission, dexamethasone (10 mg qid) should be given 15 to 20
min before the 1st antibiotic dose and continued for 4 days. This reduces seizure frequency,
consciousness level and risk of cardiorespiratory failure, unfavorable outcome, and death. A
single i.m. dose of an oily suspension of chloramphenicol has been shown to be as effective in
meningococcal meningitis as a 5-day course of crystalline penicillin. This approach is often used
during an epidemic in a developing country. Rifampicin 600 mg bid for 2 days or ciprofloxacin
500 mg one single dose or ceftriaxone 250 mg one single dose IM is effective for
chemoprophylaxis against meningococcal disease. Vaccination against meningococci covers for
A, C, Y and W-135 serogroups and may last up to 10 years.
The mortality rate is around 30% in S. Pneumoniae and 10% in N. meningitides. Death
occurs in 40% of patients with seizures.
Aseptic (serous) meningitis
Viral meningitis: Viral meningitis (most commonly enterovirus in particular echovirus)
is characterized by predominantly lymphocytic pleocytosis with normal CSF glucose and small
and variable increase in protein, and positive CSF PCR. An exception to this rule are viral
infections with HSV-2, lymphocytic choriomeningitis (often also associated with 1000s of
lymphocytes) and VZV, which may occasionally display CSF glucose levels between 25 and 40
mg/dl. The diagnosis of viral meningitis is finally based on complement fixation or ELISA
techniques by showing a 4x increase in titer from acute to convalescent serum drawn at least
with 10 days interval. Viral culture sensitivity is only 70%. HSV-2 aseptic meningitis is the main
neurologic complication of HSV-2 infection. HSV-2 causes genital herpes and is in the West the
3rd most common cause of benign recurrent aseptic meningitis, accounting for approximately
5% of all cases. Unlike viral meningitides that have a seasonal association, HSV-2 meningitis
occurs at any time of year. Meningitis may be preceded by recent symptoms of pelvic
inflammatory disease or associated penile or scrotal pain. Careful search for vesicular lesions
over the external genitalia and a pelvic examination for lesions in the vagina or on the cervix
should be done. PCR has revealed that the primary agent causing benign recurrent lymphocytic
meningitis is HSV-2. HSV-2 meningitis is self-limiting; treatment with acyclovir is not required.
Occasionally, HSV-1 is the culprit, as evidenced by the detection by CSF PCR of HSV-1 DNA
of patients with benign recurrent lymphocytic meningitis. In contrast, low CSF glucose levels are
usually observed in TB (lymphocytic pleocytosis + cranial polyneuropathy + low CSF glucose +
fever) and fungal meningitis (particularly in later stages of the disease), neoplastic disease
(metastatic carcinoma, lymphoma, meningeal carcinomatosis) (lymphocytic pleocytosis + cranial
polyneuropathy + normal or slightly decreased CSF glucose + afebrile), and sarcoidosis of the
meninges. Mycoplasma infections, cat-scratch fever and Q fever may also result in aseptic
meningitis. HIV meningitis (a sign of seroconversion) may often be associated with cauda
equina neuritis. Other viruses include CMV (immunocompromised), mumps (unvaccinated),
West Nile fever virus (Americas, Africa, West Asia, Australia, mainland Europe), tick-borne
encephalitis (mainland Europe and Asia) and St. Louis encephalitis virus (Southern states of the
US). Aseptic meningitis can also be caused by infections thought to be induced by viruses such
as Kikuchi-Fujimoro disease (histiocytic necrotizing lymphadenitis).
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TB meningitis: TB meningitis is usually a reactivation of a dormant subcortical or
meningeal focus. Risk factors for TB meningitis are age, malnutrition, alcoholism, diabetes
mellitus, chronic corticosteroid therapy and HIV-1. The clinical presentation of TB meningitis
consists of the following triad: low-grade fever (up to 98%), meningeal findings (88%) and focal
neurologic signs. TB meningitis is usually indolent, with an insidious prodrome characterized by
malaise, fatigue, low-grade fever, intermittent headache, vomiting and personality changes. This
is followed by development of meningeal syndrome with 2 to 3 weeks. However both extremes
are possible: acute bacterial-like meningitis picture or slowly progressive dementia-like
syndrome over months or years. Focal neurologic signs consist of uni-or bilateral cranial nerve
palsies (VI > III, IV and VIII). Symptoms of tuberculomas are often limited to fits and
papilledema. The mean duration of symptoms is weeks to months. Only 30% of patients with
tuberculomas have evidence of tuberculous infection outside the CNS. Chest films show
abnormalities in about 50-80% of patients with TB meningitis. ESR and WBC may be normal or
slightly increased. CSF opening pressure is increased ranging from 180-300 mm H2O. CSF
glucose is usually ≤40 mg/dL (<2.2 mmol/L) and protein 150 or >200 mg/dL. In 10-20% of
cases glucose in CSF is normal. CSF contains usually between 50-500 cells, which may be
neutrophils and lymphocytes in equal amounts. Later on lymphocytes predominate. CSF acid–
fast smears are positive in 8-86% of patients. CSF cultures are positive in <50% of patients.
Increased CSF adenine deaminase levels are a sensitive marker for TB meningitis. PCR for
detecting fragments of mycobacterial DNA in CSF specimens is positive in 83-100% of cases.
No pathognomonic neuroimages exist for TB of the CNS. MRI (T1) may show hydrocephalus,
leptomeningeal enhancement postcontrast administration, medium or small vessel infarction or
tuberculomas.
The clinical diagnosis may be considered if the three criteria are positive: CT scan brain
suggestive of hydrocephalus, edema or basal enhancement + positive chest X-ray + good
response to clinical therapy.
Irrespective of the results of individual tests, if TB meningitis is seriously suspected, it is
far better to start treatment immediately and reconsider the diagnosis when the dust has settled.
CSF changes remain positive for a period of 10 to 14 days after therapy has been initiated and
may increase despite the therapy. Classical tetra therapy (INH, rifampicin, pyrazinamide,
ethambutol or streptomycin) is used, some of them for a prolonged period 18-24 months.
Steroids should only be used in case of life-threatening subarachnoidal block or raised
intracranial pressure (above 20 mmHg). Up to 30% have severe residual sequelae such as mental
impairment, seizures, visual and oculomotor disorders, deafness and hemi- or quadriparesis, the
latter often as a result of vasculitis in the vessels of the circle of Willis, the vertebrobasilar
arteries, and perforating branches of the middle cerebral artery.
Non-TB mycobacteria or atypical mycobacteria include M. avium, M. kansasii and M.
fortuitum. These can occur in immunocompetent or immunocompromized patients.
Treatment consists of quadritherapy: INH (300 mg od plus 50 mg vitamin B6),
rifampicin (600 mg od), ethambutol (800 mg od), pyrazinamide (25 mg/kg/d or 1,500 mg/d) for
3 months followed by 6 months tritherapy. Add dexamethasone 10 mg q6h for 5 days to taper
gradually over 2 months if increased intracranial pressure, visual failure, CSF protein > 5 g/l,
focal CNS signs or prominent encephalitis. A second LP, 48 hours after the first is justified to
assess the response to treatment. 30% of patients die despite anti-TB therapy.
Syphilitic meningitis: This type of meningitis presents with meningismus, headache and
fever. Cranial nerve palsies are found in 45% of patients. Meningovascular syphilis is
characterized by weeks to months of episodic prodromal symptoms and signs, including
headache or vertigo, personality and behavioral changes, insomnia and seizures. In addition focal
neurologic deficits occur reflecting the vascular ischemic effects. Both serum RPR and VDRL,
and FTA have a specificity of 97 to 99%; RPR sensitivity is 71% and FTA-ABS sensitivity is
96%. The diagnostic requirements for neurosyphilis consist of: reactive VDRL and TPA-ABS
tests in CSF with compatible case pleocytosis (CSF WBC count >10/mm3) and CSF protein
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elevated (> 0.50 g/l). CSF VDRL has low sensitivity (22-69%), and may however be positive in
only 30% of late syphilis cases. Due to contamination possibility, a reactive VDRL on CSF in
the absence of blood contamination is sufficient to diagnose neurosyphilis, but a nonreactive
result does not exclude the diagnosis. Hence a positive VDRL always needs to be confirmed by
FTA-ABS. Although nonreactive CSF FTA-ABS test rules out the likelihood of syphilis, the
diagnosis of neurosyphilis is still based on elevated CSF WBC (>10/mm3) and/or protein CSF in
the appropriate clinical and serologic setting. False-negative syphilis tests occur in patients with
HIV infection. Treatment consists of 18 to 24 million IU of intravenous penicillin each day for
10 to 14 days. CSF leukocyte count should decrease within 6 months after therapy. Protein levels
are expected to drop at a slower rate and normalize within 2 years. CSF VDRL is also useful for
monitoring the effect of antibiotic therapy for syphilis. Although CSF VDRL titers decrease, it
may be years before they become nonreactive.
Cryptococcal meningitis: This fungal infection is ubiquitous and occurs most commonly
in patients who are immunosuppressed (HIV-1, reticuloendothelial malignancies, sarcoidosis,
organ transplantation, collagen vascular disease, diabetes mellitus, chronic hepatic failure,
chronic renal failure and patients on corticosteroids). Despite this, healthy individuals can be
affected too. 5-10% of AIDS patients develop cryptococcal meningitis. In non-AIDS patients,
cryptococcal meningitis is typically a subacute process (days or weeks) consisting of headache,
fever, meningismus, and personality change. Ocular abnormalities and cranial nerve palsies are
common but usually at later stages. In AIDS patients, the presentation is more subtle sometimes
presenting with only headache, fever and lethargy, in the absence of meningeal signs. The CSF
opening pressure is usually >200 mm H2O. Most non-AIDS patients have lymphocytic
pleocytosis (20-500 cells/mm3), with occasionally eosinophilia. CSF protein is usually increased
and glucose normal or subnormal. In AIDS patients CSF may be normal. CSF India ink
examination remains a rapid, effective test that is positive in 50-75% of cases. Latex
agglutination test is both sensitive and specific and titers of 1/8 are considered diagnostic. The
yield of CSF cultures is very high (96%) but requires long time. Alternatively serum and CSF
antigen (90% sensitive) detection can be used. MRI may show hydrocephalus, multiple
nonenhancing cystic periventricular masses in the basal ganglia but is often normal. Basilar
meninges may enhance after gadolinium administration. CSF should be recultured at the end of
10 weeks.
Coccidioidomycosis meningitis: Most commonly seen in the southwestern US, the
Central Valley of California, northern Mexico, and parts of Central and South America. C.
immitis rarely disseminated to CNS. Predisposing factors for dissemination are old age,
pregnancy, corticosteroids therapy, antitumoral chemotherapy, immunosuppression, and HIV
infection. The meningitis is usually subacute or chronic with patients complaining of headache,
low-grade fever, weight loss, and mental status changes. Signs of meningismus are usually
absent. CSF findings are typical for fungal meningitis (variable opening pressure, moderately
elevated (20-500) WBC counts, elevated protein, low CSF glucose (often < 40 mg/dL), and
negative gram stains) and can be sometimes normal. The diagnosis depends upon the
demonstration of elevated serum concentrations of complement-fixing antibodies (titers >1/32 to
1/64 suggest dissemination). Occasionally CSF may reveal prominent eosinophilia. CSF cultures
are positive in 25-50% of patients with meningitis. Fluconazole is effective therapy for
coccidioidal meningitis.
Histoplasmosis meningitis: Histoplasmosis is common in the Mississippi and Ohio river
valleys. H. capsulatum may develop without evidence of systemic infection and even in
immunocompetent patients. Chronic corticosteroid therapy is a risk factor for disseminated
histoplasmosis. Meningitis occurs in 10-20% of patients with disseminated histoplasmosis. The
symptoms are headache and fever and occasionally focal neurologic deficits. Mental status
abnormalities may occur. Pulmonary lesions may be mild, resolving or asymptomatic. Repeated
LP may be required. CSF may show signs of chronic meningitis (raised protein, decreased
glucose and lymphocytic pleocytosis). CSF and blood cultures may be negative. Immunological
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studies include yeast phase and mycelial phase. CSF, serum and urinary histoplasma antigen may
provide the diagnosis in cases of dissemination. MRI may show hydrocephalus and meningeal
enhancement after gadolinium injection. Brain and meningeal biopsy may be required.
Candida meningitis: Candida species are ubiquitous but infections commonly occurs in
patients receiving corticosteroids, broad-spectrum antimicrobial therapy; in patients with
malignancies, neutropenia, sarcoidosis, collagen vascular disease, diabetes mellitus, and in
patients with central venous catheters. Candidal meningitis is nonspecific. The onset can be
either abrupt or insidious and the clinical manifestations can be differentiated from other forms
of fungal meningitis. CSF pleocytosis (600 cells/mm3), lymphocytes or neutrophils. Yeast is
detected in 50% of cases on direct microscopy of CSF. A single positive culture from a patient
with risk factors or symptoms is considered significant when CSF indices are compatible and the
fungus is isolated in pure culture.
Actinomycetes, Nocardia, and pseudallescheria occurs almost exclusively in
immunocompromised patients (Hodgkin and non-Hodgkin disease, multiple myeloma, solid
tumors, long-term use of steroids, chronic obstructive pulmonary disease, alveolar proteinosis,
SLE, vasculitis, Cushing disease, chronic liver disease, hemochromatosis, RA, sarcoidosis, TB,
diabetes, alcoholism, chronic granulomatous disease, solid organ or bone marrow
transplantation, AIDS). Pseudallescheria boydii presents as brain abscess and occasionally as
meningitis. The infection becomes manifest 2-3 weeks after an episode of near drowning. Biopsy
is diagnostic. Nocardia results in 70% from lung infections. In the presence of nocardia
meningitis (CSF show pleocytosis (83%), reduced glucose (64%) and protein >100 (61%)) brain
abscesses may result in 20-40% of cases.
Primary amebic meningoencephalitis: Exposure to contaminated pools and water may
result in infections with amoebae (Naegleria fowleri and Acanthamoeba). In the acute form,
following an incubation period of 3-8 days, there is sudden onset of high fever, photophobia and
headache with or without focal neurologic signs. CSF shows neutrophilic pleocytosis, low
glucose and elevated protein and red blood cells. Examination of fresh warm specimens of CSF
can reveal trophozoites. The subacute or chronic form presents more insidiously, with low-grade
fever, headache, and focal neurologic signs. CSF shows predominantly mononuclear cells,
normal or subnormal glucose and elevated protein. Serum immunofluorescence amebic
immobilization titers and complement-fixing antibodies support the diagnosis. Deterioration
occurs over weeks or months can occur.
Toxoplasma encephalitis: CNS toxoplasmosis is usually associated with intracerebral
mass lesions or encephalitis in immunocompromised hosts (lymphoma, leukemia, cytotoxic
therapy, organ transplantation, treatment of collagen disorders, HIV patients). The clinical
manifestations of CNS toxoplasmosis range from insidious onset evolving over weeks to an
acute confusional syndrome. Transplant patients often have diffuse and disseminated disease.
Early signs and symptoms include weakness, lethargy, confusion, seizures and headache. AIDS
patients with CNS toxoplasmosis often present with nonspecific symptoms such as
neuropsychiatric complaints, headache, lethargy and confusion. The course is progressive over 2
– 8 weeks. Patients then develop evidence of focal CNS mass lesions. The parasite has a
predilection to localize in the basal ganglia, producing an akinetic–rigid syndrome. AIDS
patients often develop a chronic encephalopathy with seizures. In AIDS patients, more than 97%
of patients with toxoplasmosis encephalitis have serum antibody titers against T. gondii ranging
from 1:8 to >1:1,024. Brain CT scan shows multiple rounded isodense or hypodense lesions with
ring enhancement after contrast administration affecting particularly the basal ganglia or
corticomedullary junction. MRI is more sensitive and is able to demonstrated diffuse
toxoplasmic encephalitis. Definitive diagnosis is based on brain biopsy with demonstration of the
pseudocysts and tachyzoites. In AIDS patients, positive neuroimaging and positive antiToxoplasma IgG serologic tests are sufficient to initiate empiric therapy for toxoplasmic
encephalitis. Negative serologic test makes the diagnosis less likely and warrants brain biopsy.
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Angiostrongylus cantonensis: This infection leads to eosinophilic meningitis. This
parasite is ubiquitous in South East Asia. Typical symptoms of meningitis start 6-30 days after
ingestion of raw mollusks. Eosinophilia is found in blood and CSF.
Uveoretinal meningoencephalitis: This form of meningitis may occur in several
conditions: a. Inflammatory diseases: 1) SLE; lupus choroidopathy occurs with significant
vasculitis, renal complications (including systemic hypertension), and rarely is associated with
retinal pigment epithelial disease or secondary retinal detachment; 2) Sarcoidosis: patients may
have uveitis and meningoencephalitis with hypothalamic involvement. The uveitis is usually
anterior rather than posterior. Moreover, retinal detachment is unusual; 3) Ocular lyme
borreliosis: can present with iridocyclitis, vitreitis, and occasionally panuveitis and retinal
detachment; 4) Other inflammatory diseases: including MS, neuroBehçet and inflammatory
bowel disease; b. Infectious diseases: 1) Syphilis: uveitis, chorioretinitis, and optic neuritis are
late manifestations; 2) Tuberculosis: Retinal changes are limited to "multifocal" granulomas,
large or small; 3) HSV and VZV can cause uveitis, conjunctivitis, keratitis, and encephalitis
follow ophthalmic zoster. HSV intraocular disease is usually a necrotizing retinitis; 4) Whipple
disease; 5) Fungal infections; 6) Other: HIV meningitis can cause a similar clinical picture with
acute meningitis 3-6 weeks after the primary infection, but the eye findings are varied (cottonwool spots being the most common). CMV causes retinitis and encephalitis in
immunocompromised patients. The same argument follows for toxoplasmosis; c. Eye/CNS
diseases: 1) Sympathetic ophthalmia can present with rapid bilateral visual loss associated with
anterior segment inflammation, disk edema/hyperemia, choroidal thickening, and serous retinal
detachments; 2) Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) is an
acute condition occurring in both men and women from 15-50 years of age classically in the
recovery phase after a viral illness and is characterized by loss of central vision associated with
the appearance of multiple pale lesions in the retinal pigment epithelium. The patients may
occasionally have papillitis and serous detachment of the retina or CNS involvement with
headache, transient ischemic attacks, dysacusis and tinnitus. It is a self-limited disease, resolving
in 2 to 3 weeks; 3) Multifocal secondary retinal and pigment epithelial detachments are also seen
in (Grade IV) systemic hypertension, and pregnancy-induced hypertension; 4) Vogt-KoyanagiHarada syndrome a recurrent form of aseptic meningitis consists of bilateral, rapid, and painful
loss of vision associated with posterior or panuveitis. It is associated with meningitis, dysacusis,
tinnitus, uveitis, or cerebrospinal fluid pleocytosis and much later with depigmentation of the
uveal tract and skin (alopecia, poliosis, or vitiligo (late)). There is a slight preponderance of
females. The age of onset is usually between the 2nd and 5th decades, with a mean age of 30 to
40 years. Multifocal and multiloculated serous pigment epithelial and retinal detachments are
seen on ophthalmoscopic exam and documented on fluorescein angiography.
USED IN THIS LESSON, NEW EDUCATIONAL TECHNOLOGY, "METHOD
OF SNOWBALLS."
USE OF THE "SNOWBALL"
SCRIPT. For no more than 10 minutes.
Two groups of students together discuss a problem or situation with a view to set the
maximum number of correct answers.
Title: Meningococcal disease, meningoencephalitis.
Each answer to the question shall be credited as a reference point in this group as
"Snowball." The group treated with the most number of points will have the highest mark.
The teacher asks each student a series of questions for a minute. With the answers are
fixed the number of correct answers, etc. The final score put up by the dialed number of points
within a one-day maximum points.
Variants of annotations:
1. The mechanism of transmission: aerogenic.
2. Source of infection: the sick person or a smear.
12
3. Differ. diagnosis of meningitis: Influenza (toxic, fulminant form).
4. What is included in the group of pyogenic meningitis? Meningococcal meningitis,
pneumococcal meningitis, staphylococcal meningitis, streptococcal meningitis, otogenic
meningitis, Pfeyfferovsky meningitis.
5. What is included in the group of serous meningitis? Tuberculosis, mumps, enterovirus,
lymphocytic.
6. What is meningoencephalitis? Inflammatory diseases of the brain, most often an
infectious-allergic genesis.
7. The causative agents of encephalitis: viruses (enteroviruses, arboviruses, measles
virus, rubella, etc.), bacteria, rickettsia, fungi, protozoa.
Eight. Which groups are divided encephalitis? Primary and secondary.
9. What is a primary encephalitis? Independent of the disease, mostly caused by
neurotropic viruses.
10. What is the secondary meningoencephalitis? Develop against the main infectious
disease or during a recession leading symptoms of the disease, with local inflammatory
processes in the head and neck, as well as an allergic reaction of the brain for many pathogens.
11. The main symptoms of meningitis: fever, headache, and vomiting.
12. What age children suffer from pneumococcal meningitis? Young children.
13. The initial signs of pneumococcal meningitis: rapid start, the temperature of 38 ° C,
pneumonia, sinusitis.
14. A characteristic feature of staphylococcal meningitis: lack of therapeutic effect of
commonly used antibiotics.
15. Initial clinical signs of streptococcal meningitis: It starts badly, vomiting, anxiety,
signs of meningoencephalitis, gepatolienalny syndrome, acute renal failure, scanty petechial
rash.
16. What kind of disease occurs with serous meningitis? Tuberculous meningitis, mumps,
enterovirus, lymphocytic.
17. What is encephalitis? Neyrovirusnaya Acute infection is characterized by lesions of
gray matter of the brain and spinal cord with subsequent development of flaccid paresis and
paralysis.
18.
Clinical
forms
of
tick-borne
encephalitis
febrile,
meningeal,
meningoentsefaliticheskaya.
19. What do you know nosological forms of secondary encephalitis? Cytomegalovirus,
rubella, chickenpox, mumps infection with encephalitis and poliomyelitis.
6.2. The analytical part
Situational tasks
Task № 1. Patient 43 years old, was admitted on the 7th day of illness. The disease
started slowly, there was general weakness, fatigue, appetite worsened. On the third day of
illness moderate headache, sleep was interrupted. At night, sweating, on the 7th day of illness the
temperature rose to 37-38,7 ° C, vomiting was one time.
On admission the patient of average weight, sluggish, adynamic. The skin is pale, moist.
Peripheral lymph nodes are small, painless. Acrocyanosis. Breathing 28 per minute. Above the
light percussion sound is not shortened, auscultatory hard breathing all over, wheezing is not
audible. Heart sounds are muffled, blood pressure 100/60 mm Hg, pulse 69 beats per minute.
Language dryish, coated with white bloom. The abdomen is soft. The liver and spleen were not
palpable. Meningeal signs are mild. Anisocoria - the left pupil is greater than the right.
At lumbar puncture fluid leaking under pressure, clear, colorless. After 24 h in a liquid
formed gentle membrane. Cytosis - 250 mm3, lymph. - 68%, Leuc. - 32%, the reaction Pandey +
+ + +. Sugar - 1520 mg / dL, protein - 96 mmol / l, chlorides - 1.0 mmol / l.
1. Your preliminary diagnosis?
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2. What are the clinical symptoms and laboratory findings, differentiate meningococcal
meningitis from tuberculosis?
№
1.
2.
Answers
Tuberculous meningitis
Meningococcal meningitis is characterized by the acute, rapid start, severe headache,
repeated vomiting without preceding nausea, hypersensitivity, psychomotor agitation,
changing soon retardation, depression, seizure syndrome, high fever, the development of
meningeal syndrome. Purulent CSF. Hyperleukocytosis.
Tuberculous meningitis starts slowly and gradually. Fever increases gradually,
meningeal syndrome gradually appears and grows, accompanied by excruciating
headaches, repeated vomiting. In the history - tuberculosis, transferred or contact with
tuberculosis patients. In no blood hyperleukocytosis, liquor clear. It follows under high
pressure. Gentle membrane is formed at standing of CSF.
Task № 2. Patient 20 years old, entered the clinic on the third day of illness with
complaints of headache, repeated vomiting, insomnia, high temperature. Ill three days ago,
marked by cold, the temperature remained within normal limits. On the 2nd day of the disease
about 17 hours, the patient appeared sharp headache, chills, temperature of up to 39,9 ° C, after a
few hours from the onset of illness occurred repeated vomiting, the next day vomiting was
repeated every 20-30 min, increased headache the pain.
At the moment of admission to hospital the patient's condition was severe, the
temperature of 38,7 ° C, retained consciousness, responds the questions with difficulty, groans
occasionally. The face is pale. On the skin of the chest, abdomen, extremities abundant
polymorphic rash with cyanotic tinge in the center of many elements of areas of necrosis. Pulse
92 beats per minute., mild, rhythmic. BP 90/60 mm Hg Cardiac sounds are muffled. In the lungs
vesicular breathing. Abdomen soft and painless. There weren’t of neck muscles rigidity.
Symptoms of Kernig and Brudzinsky are negative.
1. Your preliminary diagnosis?
2. Treatment.
№
1.
2.
Answers
Meningococcal infection, meningococcemia
Etiotropic (intensive penicillin therapy - 200000-300000 units. Per 1 kg of body weight,
5-8 days, chloramphenicol succinate, 50-100 mg per kg daily dose, sulfonometoksin.
Pathogenic - fight toxicity, in / solutions in combination with dehydration through the
use of diuretics (mannitol, Lasix, diakarb). Steroid drugs. Anticonvulsant therapy.
Symptomatic therapy.
Task №3. Patient B., aged 22, student in the past, before was not ill. The present illness
began 04.03. with the light nasopharyngitis. A day later the state has deteriorated sharply, with a
fever temperature and headache increased, there was a sharp pain in the joints. He was
hospitalized in the therapy department with a diagnosis of rheumatic fever.
At admission pallor of the skin was marked without rash. Swelling, mild redness, severe
pain and dysfunction of the joints of fingers were observed. Tachycardia, heart sounds are clear.
BP 110/60 mm Hg In the blood: Hb - 85 g / l, leuc. - 13000 / l, SN - 16%, SegN - 73%, Eos. 1%. - 1%, lymph. - 8%, Mon. - 1%, ESR - 30 mm / h
Antirheumatic therapy started (penicillin 200 000 IU every 6 hours, aspirin, prednisolone). A day
later pain in the joints decreased slightly, but vomiting was joined, meningeal signs were found.
The confusion came a day later, meningeal signs were increased. Puncture of the cerebrospinal
fluid was purulent, with a high neutrophil cell count, in blood smears and inoculation diplococci
were revealed.
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1. What disease you can think about?
2. What day of the disease does exanthema appear?
№
1.
2.
Ответы
Meningococcal infection, meningitis
Rheumatic fever, collagenosis, serous meningitis.
6.3. The practical part
Determination of meningeal symptoms and pathological reflexes.
Purpose: Identification of meningeal syndrome.
Indications: Diseases accompanied by phenomena of meningitis and
meningoencephalitis.
Necessary equipment: couch, mask.
Performed steps :
№
measure
Not
Partially
Fully
completed completed
correctly
(0 points)
(5 points)
completed
(10 points)
1. The physician must be in the mask. Severe
headaches defined
0
5
10
2. Place the patient on the couch
0
5
10
3. Define the neck muscles rigidity
0
5
10
4. Define Kernig's symptom on both sides
0
5
10
5. Define the upper symptom of Brudzinsky
0
5
10
6. Define the medium symptom of Brudzinsky
0
5
10
7. Define the lower symptom of Brudzinsky
0
5
10
8. Define the symptom of Lessazh
0
5
10
9. Define the abdominal reflexes
0
5
10
10. Define pathologic reflexes (Бабинского,
Россолимо, Оппенгеймера)
0
5
10
Всего
0
50
100
LUMBAR PUNCTURE
Indications
1. Suspected CNS infection
2. Suspected subarachnoid hemorrhage
3. Therapeutic reduction of cerebrospinal fluid (CSF) pressure
4. Sampling of CSF for any other reason
Contraindications
1. Local skin infections over proposed puncture site (absolute contraindication)
2. Raised intracranial pressure (ICP); exception is pseudotumor cerebri
3. Suspected spinal cord mass or intracranial mass lesion (based on lateralizing neurological
findings or papilledema)
4. Uncontrolled bleeding diathesis
5. Spinal column deformities (may require fluoroscopic assistance)
6. Lack of patient cooperation
15
Materials
1.Lumbar puncture tray (to include 20 or 22 gauge Quinke needle with stylet, prep solution,
manometer, drapes, tubes, and local anesthetic)
2.Universal precautions materials
Preprocedure patient education
1. Obtain informed consent
2.Inform patient of possibility of complications (bleeding, persistent headache, infection) and
their treatment
3. Explain the major steps of the procedure, positioning, and postpocedure care
Procedure
1.Assess indications for procedure and obtain informed consent as appropriate
2.Provide necessary analgesia and/or sedation as required
3.Position patient: lateral decubitus position with “fetal ball” curling up, or seated and leaning
over a table top; both these positions will open up the interspinous spaces (see Figure 1)
4. Locate landmarks: between spinous processes at L4-5, L3-4, or L2-3 levels. On obese
patients, find the sacral promontory; the end of this structure marks the L5-S1
16
interspace. Use this reference to locate L4-5 for the entry point. You will aim
the needle towards the navel.
5.Prep and drape the area after identifying landmarks. Use lidocaine 1% with or without
epinephrine to anesthetize the skin and the deeper tissues under the insertion site
6.Assemble needle and manometer. Attach the 3-way stopcock to manometer
7.Insert Quinke needle bevel-up through the skin and advance through the deeper tissues. A
slight pop or give is felt when the dura is punctured. Angle of insertion is on a slightly cephalad
angle, between the vertebra (Figure 3). If you hit bone, partially withdraw the needle, reposition,
and re-advance
8. When CSF flows, attach the 3-way stopcock and manometer. Measure ICP…this should be 20
cm or less. Note that the pressure reading is not reliable if the patient is in the sitting position
9. If CSF does not flow, or you hit bone, withdraw needle partially, recheck landmarks, and readvance
10.Once the ICP has been recorded, remove the 3-way stopcock, and begin filling collection
tubes 1-4 with 1-2 ml of CSF each
Tube 1: glucose, protein, protein electrophoresis
Tube 2: Gram’s stain, bacterial and viral cultures
Tube 3: cell count and differential
Tube 4: reserve tube for any special tests
11.After tap, remove needle, and place a bandage over the puncture site. Instruct patient
to remain lying down for 1-2 hours before getting up
NOTES:
1. Insertion of the needle bevel-up minimizes dural trauma
2. A traumatic “bloody tap” occurs when a spinal venous plexus is penetrated. Often the fluid
will clear as succeeding tubes are filled. Spin down the first tube: if red blood cells have been in
the spinal fluid for some time (for example, subarachnoid hemorrhage), xanthochromia will be
present in the supernatant fluid. If the fluid is clear after it is spun down, the tap was only
traumatic
3. In some cases, conscious sedation is helpful in reducing patient anxiety and allowing maximal
spinal flexion
8. The recommended literature
1. Majidov V.M. Infectional diseases. Т., 1992.
2. Maxmudov O.S. Children inflectional diseases, Т., 1995.
3. Uchaykin V.R. Manual by children inflectional diseases, М.,2005.
4. Shuvalova E.P. Infectional diseases, М.,1999.
5. Musabaev I.K. «the Management on intestinal infections», Т, 1999.
7. Pokrovsk Century И, Pak Of this year, etc. «Infectious diseases and epidemiology». - М,
2003
8. Jushchuk N.D., Vengerov J.J. «Lectures on infectious diseases». - М, 1999.
9. Uchajkin V. F «the Management on infectious diseases at children», - М, 1998.
10. Internet resources (www <http://www.medlinks.ru/> medlinks
<http://www.medlinks.ru/><http://www.medlinks.ru/>ru <http://www.medlinks.ru/>,
www.cdc.gov <http://www.cdc.gov/>).
17