infections of the nervous system - cuni.cz
TRANSCRIPT
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Infections of the Nervous System
Introduction
Involvement of CNS during infection
when a microorganism gain access to the CNS
or by the immunopathologic mechanisms =
neuroinfections
by vascular, metabolic and toxic processes =
toxoinfectious encephalopathies (non-
inflammatory response of the CNS to infection)
Classification of NS Infections (1)
by localization of the disease process
* central nervous system
meningitis
encephalitis
myelitis
* peripheral nervous system
radiculitis
neuritis
* combined involvement
meningoencephalitis
encephalomyelitis
polyradiculoneuritis
Classification of NS Infections (2)
by character of the inflammatory response
* purulent
* aseptic
* specific
by clinical course
* acute
* subacute
* chronic
Clinical Manifestations
Meningitis:
• sudden onset (in acute meningitis)
• fever
• headache
• meningismus
• altered mental status (in acute bacterial meningitis)
Encephalitis:
• altered mental status (24 h)
• fever (3 days)
• seizures
• (new-onset) focal neurol. finding
• CSF finding (pleocytosis)
• (new) neuroimaging abnormality
• EEG abnormality consistent with encephalitis
presents with
Meningism (1)The meningism includes symptoms and signs which appear as a
result of meningeal irritation by
* inflammation
* hemorrhage
* neoplasm
* increased intracranial pressure, high temperature etc.
Symptoms:
* headache
* vomiting
* irritability, hyperesthesia, photophobia etc.
Signs:
* meningeal signs – inflammed sensory roots produce a reflex
contraction of muscles, particularly paravertebral
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Meningism (2)Lumbar Puncture (1)
LP with removal and analysis of CSF is an
essential procedure in the diagnosis of
meningitis and encephalitis
Indications for LP:
* To obtain CSF in a suspicion of meningitis
* Reduction of raised intracranial pressure
* Lumbar intrathecal instillation of drugs
Lumbar Puncture (2)
Contraindications for LP:
Mass lesion or very increased intracranial pressure (possible
danger of herniation - tentorial or cerebellar coning) Some
evidence for this circumstance are
rapidly developing depression of consciosness (coma)
focal neurologic signs
convulsions
papilledema.
Significant coagulopathy (possible danger of bleeding)
Infected lumbar area (possible danger of infection)
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Lumbar Puncture – contd.
Some complication have been associated with performance of the LP - ranging from mild problems to the most feared herniation:
mild discomfort with insertion of the spinal needle
frequent postpunction headache and neck stiffness (10-25% patients)
nerve root irritation
local bleeding (rarely does harm to the pt, although pts with coagulopathy or receiving anticoagulants)
infection with susequent meningitis (1/50 000 procedures)
brain herniation
CSF Examination (1)
ROUTINE INITIAL TESTS
Cytology
cell count
cell type
Chemistry
protein
glucose
lactate
chloride
Fuchs-Rosenthal´s
counting chamber
(volume 3 ul)
CSF Examination (2)
Typical CSF Findings
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CSF Examination (3)
ROUTINE TESTS ACCORDING TO RESULTS
OF INITIAL STUDIES
If purulent CSF pattern:
Microbiology:
Gram´s staining
latex agglutination
bacterial cultures
DNA (by PCR)
If aseptic CSF pattern:
Serologic and molecular
genetic tests:
PCR enteroviruses
Lyme disease serology
HSV-1 DNA by PCR (if
confusion, altered
personality, seizures)
CSF Examination (4)
SPECIAL STUDIES
If special suspicion:
Cytology:
smear of the sediment
immunocytology
Chemistry:
oligoclonal bands
immunoglobulins
CSF Examination (5)
ROUTINE TESTS ACCORDING TO RESULTS
OF INITIAL STUDIES
Microbiology:
india ink
fungal cultures
mycobacterial studies
Cryptococcal Ag
electron microscopy
(Borrelia burgdorferi)
Virology:
viral cultures
PCR
electron microscopy
(JCV)
Serologic tests:
syphilis serology
CSF Examination (6)
Other CSF Findings
Fungal or tuberculous meningitis:
Cell count: low mixed pleocytosis
Protein: high
Glucose: low
Chloride: low
Parameningeal infl. focus (brain abscess, endocarditis):
Cell count: low mixed or polymorphonuclear pleocytosis
Protein: high
Glucose: normal
Chloride: normal
CSF Examination (7)
Other CSF Findings
Guillain-Barré syndrome:
Cell count: low lymphocytar or normal pleiocytosis (max. 50/3 ml)
Protein: high (usually about 1 g/l)
Glucose: normal
Chloride: normal
Meningitis
= an inflammation of the meninges
characterized by pleocytosis
It is very important to distinguish
acute bacterial (purulent) meningitis
acute aseptic (serous) meningitis
chronic meningitis
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Acute Bacterial Meningitis (1)
Meningitis purulenta acuta
Incidence: 2-3/100.000
Etiology: Major causative organisms (90 %)
Streptococcus pneumoniae (pneumococcus)
Neisseria meningitidis (meningococcus)
Haemophilus influenzae
Epidemiology: most diseases - sporadic,
meningococci A et C - epidemic too
Acute Bacterial Meningitis (2)
Pathophysiology:
routes of infection
hematogenous
per continuitatem
direct invasion (penetrating head trauma,
meningomyelocele)
Acute Bacterial Meningitis (3)
Primary
Secondary
head trauma - penetrating or closed (pneumococcus,
staphylococcus, G- bacilli)
chronic otitis media (pneumococcus)
sinusitis (pneumococcus, Haemophilus)
neurosurgery (G- bacilli, staphylococcus, anaerobes, Nocardia)
CSF shunt (Staphylococcus epidermidis, S. aureus, G- bacilli,
diphteroids)
Acute Bacterial Meningitis (4)
Clinical manifestations
Symptoms:
rapid onset
fever
headache
vomiting
confusion
others: seizures, skin rash, myalgias
Acute Bacterial Meningitis (5)
Clinical manifestationsSigns: - fever
meningismus
other neurologic and related findings
altered consciousness
cranial nerve palsies
signs of increased intracranial pressure (HR, BP,
breathing, cranial nerves involvement)
focal neurologic signs (hemiparesis, aphasia)
skin rash (petechiae), oral herpes
signs of shock
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Acute Bacterial Meningitis (6)
Tests:
(ESR: very high)
BC: leucocytosis
CRP: very high
CSF: polymorphonuclear pleocytosis, high protein level,
hypoglycorrhachia
Course:
acute - fulminant
Acute Bacterial Meningitis (7)
Complications and Sequelae
Complications:
Intracranial complications:
cerebral abscess
subdural and epidural empyema
thrombophlebitis of venous sinus
subdural effusion (hygroma subdurale)
obstructive hydrocephalus
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Acute Bacterial Meningitis (8)
Other neurologic sequelae:
cranial nerve palsies
motoric involvement (for example hemi- or quadruparesis,
ataxia)
Specific complications of meningococcaemia:
myocarditis and pericarditis
metastatic or reactive arthritis
disseminated intravascular coagulopathy (DIC)
Watterhouse-Friderichsen´s syndrome
Acute Bacterial Meningitis (9)
Non-specific complications:
pneumonia
urinary tract infections (UTI)
intravenous catheter-related bacteremia or sepsis
Sequelae:
hearing loss (deafness)
behavioral disturbances, mental retardation
visual problems
motoric involvement (permanent paralysis)
secondary epilepsy
Acute Bacterial Meningitis (10)
Diagnosis
History: chronic otitis media, surgery
(polypectomy) and head trauma
Symptoms and signs: fever, headache,
meningism and signs of cerebral dysfunction
(declining level of consciousness)
Laboratory data: CSF - pyogenic formula, ESR,
BC, CRP - consistent with bacterial infection
Acute Bacterial Meningitis (11) Other and additional examinations:
Hemocoagulation
Chemistry
Blood cultures
Fundoscopy (because excluding of papilledema)
X-ray (of chest, skull, mastoids, sinuses), CT scans, MRI,
brain ultrasonography (in infancy)
ENT exam
Audiogram
Radioisotopic scanning
Acute Bacterial Meningitis (12)
Prognosis
Prognosis: serious
Mortality: 10-20% (despite therapy!)
Prognosis depends upon many factors,
including the following:
the causative microorganism
the age of the patient
the underlying diseases
Acute Bacterial Meningitis (13)
Therapy
Antibiotics:
Third-generation cephalosporins (i.g.
cefotaxime, ceftriaxone)
Ampicillin (add if Listeria meningitis is not
excluded)
Others: penicillin G, meropenem,
chloramphenicol, vancomycin
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Acute Bacterial Meningitis (14)
Therapy Dexamethasone (0.15mg/kg q4-6h IV)
should be given concomitant with or just before the first antimicrobial dose
improves outcome
may be beneficial in reduction of cerebral edema
reduction of risk of hearing loss
Reduction of intracranial pressure:
Mannitol 20% (1.0-1.5ml/kg q4-6h IV)
Other supportive care and symptom-based therapy
Infusions, antipyretics, anticonvulsants, mechanical ventilation
Treatment of complications (e.g. surgical Rx: AME)
Acute Bacterial Meningitis (15)
Prevention and Prophylaxis
Vaccination
H. influenzae: H. influenzae type b (Hib) conjugate vaccine
N. meningitidis: meningococcal vaccine – teravalent conjugate (active
against serogroups A, C, Y, and W135) and recombinant (against B)
S. pneumoniae: 13-valent conjugate vaccine
Chemoprophylaxis
N. meningitidis: penicillin, macrolids, rifampicin
Acute Aseptic Meningitis (1)
Meningitis serosa (acuta)
Incidence: 10/100.000
Etiology:
Viruses
Enteroviruses
Arboviruses (TBE virus)
Herpesviruses (associated with primary genital infection
with HSV-2)
Acute Aseptic Meningitis (2)
Virus influenzae and other respiratory viruses
Human immunodeficiency virus (HIV-1)
Lymphocytic choriomeningitis virus (LCM)
Bacteria
Borrelia burgdorferi
Leptospira spp.
Mycoplasma pneumoniae
Pathogenesis:
during the viremia, the viral agent invades the CNS
Acute Aseptic Meningitis (3)
Clinical manifestations:
Symptoms:
headache and fever
Signs:
meningeal signs
Tests:
ESR, hematologic and biochemical parameters:
nonspecific
Course: acute, often biphasic
Acute Aseptic Meningitis (4)
Diagnosis:
Exposure history: suspicion of a tick-transmitted
disease
Clinical manifestations: suspicion of meningitis
CSF: lymphocytic pleocytosis
Serologic tests: antibody against causative agents
Complications and sequelae:
occur rare
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Acute Aseptic Meningitis (5)
Differential diagnosis:
Other forms of meningitis (bacterial, tuberculous,
mycotic)
Systemic illnessis with fever and meningeal
irritation
Subarachnoid hemorrhage
Cervicocranial syndrome
Prognosis:
good
Acute Aseptic Meningitis (6)
Therapy:
Confinement to bed
(Mannitol, corticosteroids)
Antipyretics, antiemetics, vitamins
Prevention:
Prevention from tick-bite
Vaccination against mumps, rash diseases etc.
Vaccination against TBE (FSME-Immun, Encepur)
Encephalitis
• Encephalitis is defined as inflammation of the
brain parenchyma associated with neurologic
dysfunction
• Accurately:
Acute Encephalitis (1)
Incidence: 10/100.000
Etiology:
Viruses
Arboviruses (TBE virus … VNF)
Virus influenzae and other respiratory viruses,
measles virus
Herpesviruses (HSV-1, -2, VZ virus, EBV, CMV etc.)
Enteroviruses, HIV, rabies virus
Acute Encephalitis (2)
Bacteria
Borrelia burgdorferi
Rickettsia rickettsii
Chlamydia psittaci
Chlamydophilla pneumoniae
Mycoplasma pneumoniae
Acute Encephalitis (3)
Parasitic agents
Trypanosoma spp.
Acanthamoeba
Naegleria spp.
Toxoplasma gondii
Plasmodium spp.
Immunisation
Vaccine against measles, mumps, etc.
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Acute Encephalitis (4)
Pathogenesis:
Encephalitis
primary - direct invasion of causative agent
postinfectious and parainfectious -
immunopathologic mechanisms
Acute Encephalitis (5)
General symptoms and signs
fever
headache
decreased consciousness
movement disorders (pareses, dyskinesis, ataxia)
cranial nerve defects
tremor
seizures
Acute Encephalitis (6)
Specific forms of encephalitis
herpes simplex encephalitis (necrozing encephalitis)
cerebellitis (acute cerebellar ataxia, gait disturbances) -
chicken pox
brain stem encephalitis (life-threatening symptoms and
signs)
focal encephalitis (focal seizures, hemiparesis, aphasia)
poliomyelitis anterior acuta
rabies
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Acute Encephalitis (7)
Diagnosis Exposure history: tick-bite
Clinical manifestations: neurologic symptoms and signs
CSF: mild lymphocytic pleiocytosis
EEG: diffuse slowing
CT: normal or diffuse brain edema
Serologic tests: antibody against causative agents
Virologic tests: isolation of viral agent, nucleic acid
techniques
Other microbiologic tests: detection of infectious agent
Acute Encephalitis (8)
Differential diagnosis
Metabolic diseases (uremic, hepatic encephalopathy, etc.)
Toxic disorders (drug intoxication)
Mass laesions (tumor or abscess)
Acute demyelinating disorders (acute multiple sclerosis, acute
haemorrhagic leukoencephalitis)
Status epilepticus (especially non-convulsive status epilepticus,
complex-partial status, absence status)
Toxoinfectious encephalopathies (Reye´s syndrome, malaria, etc.)
Thrombophlebitis of venous sinus
Rare: SSPE, PML, Jacob-Creutzfeldt´s disease
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Acute Encephalitis (9)
Prognosis:
generally: good
herpetic necrosing encephalitis: life-threatening
rabies: fatal
Therapy:
Causal: acyclovir 3x 10mg/kg/day i.v.
Supportive and symptom-based: Confinement to
bed, mannitol, corticosteroids, antipyretics,
antiemetics, anticonvulsants, nootropic agents
Guillain-Barré Syndrome (1)
Polyradiculoneuritis acuta
Incidence:1/100.000
Etiology:
Infection:
viral (EBV, CMV, HIV, HAV, HBV, TBE virus)
bacterial (Campylobacter jejuni)
Systemic disease:
SLE, Hodkin´s disease, sarcoidosis, HIV infection
Unknown
Guillain-Barré Syndrome (2) Pathogenesis:
Autoimmune mechanisms - demyelination -
conduction block - paresthesias, pain and
weakness
Clinical manifestations:
Symptoms:
prodromal influenza-like or diarrheal illness
fine parestesias to pain in the toes or fingertips
progressive weakness in both legs, then both arms
follows (lead to walking and climbing stairs difficult)
Guillain-Barré Syndrome (3) Signs:
cranial-nerve involvement
bilateral weakness of facial muscles
ophthalmoplegia
weakness
relative symmetric
acral maximum
lower extremity > upper extremity
diminished tendon reflexes to areflexia
Guillain-Barré Syndrome (4) mild sensory loss
autonomic dysfunctions
difficulty swallowing
hypoventilation
constipatio
Tests:
ESR, BC, CRP: nonspecific
CSF: proteinocytologic dissociation
(lymphocytes < 50/3, protein level >0,8 g/l)
EMG: typical feature
Guillain-Barré Syndrome (5)
Course: Weakness
stops advancing in one to three weeks
slowly improves after a plateau lasting several weeks
Clinical variants:
Fischer´s syndrome (which involves ophthalmoplegia,
ataxia, and areflexia)
Chronic inflammatory demyelinating polyneuropathy,
CIDP (tends to progress for more than four weeks,
relapsing course)
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Guillain-Barré Syndrome (6)
Complications:
ARDS
Pulmonary embolism
Cardiac arrest
Sequelae:
residual motoric or sensory deficit
Diagnosis:
Clinical manifestations, CSF feature, EMG feature
Guillain-Barré Syndrome (7)
Complications:
ARDS
Pulmonary embolism
Cardiac arrest
Sequelae:
residual motoric or sensory deficit
Diagnosis:
Clinical manifestations, CSF feature, EMG feature
Guillain-Barré Syndrome (8)
Differential diagnosis:
Spinal cord compression
Transverse myelitis
Myasthenia gravis
Basilar-artery occlusion
Myopathies
Neuropathies
Botulism
Bannwarth´s syndrome
Tick paralysis
Guillain-Barré Syndrome (9)
Prognosis: usually: recovery over a period of weeks or
months, mortality: 5%
Therapy:
Immunoglobulins (0.4g/kg/day x 5 days)
Plasma exchange
(Corticosteroids)
Chest physical therapy to mechanical ventilation
Anticoagulants (prevent from pulmonary embolism)
Rehabilitation