Infections of the Nervous System - cuni.cz

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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