Infections of the Nervous System -

Bacterial Infections

Acute Bacterial Meningitis

Definition: Acute purulent infection within the

subarachnoid space Pia-arachnoid Cerebrospinal fluid

Brain parenchyma frequently involved Meningoencephalitis

Epidemiology

Most common of suppurative CNS infection Incidence: 3-5/100 000

Highest in the first month of life Nearly 75% occur in children under 15

Vaccination led to: Dramatic decline in the incidence of Haemophilus

influenzae meningitis Smaller decline in Neisseria meningitidis

meningitis

Community-Acquired Meningitis:Etiology

Streptococcus pneumonia-50% N. Meningitidis-25% Group B streptococci-15% Listeria monocystogenes-10% H. Influenzae- less than 10%

Pathophysiology

Colonization of nasopharynx Bacteremia and infection of choroid plexus Invasion of the subarachnoid space and

multiplication in CSF Induction of inflammatory reaction:

Release of inflammatory cytokines Upregulation of adhesion molecules Granulocyte penetration into CSF and further

release of inflammatory mediators

Pathophysiology

Increased vascular permeability causes vasogenic edema

Toxins released by bacteria and granulocytes lead to cellular damage and loss of cellular homeostasis and worsen cerebral edema

Obstruction of CSF leads to hydrocephalus Vasculitis and Thrombosis leads to infarction Cerebral herniation

PUS IN SUBARACHNOID SPACE

VIRCHOW-ROBIN SPACE

Pathophysiology

Parameningeal structures: Ears, paranasal sinuses Osteomyelitic foci in the skull Congenital sinus tracts Penetrating cranial injuries

Iatrogenic source : Brain or spine surgery Ventriculoperitoneal shunt Rarely post- lumbar puncture).

Undetermined

Clinical Presentation

Onset: Acute fulminant-few hours Subacute-over several days

Classic clinical triad: fever,headache and nuchal rigidity (stiff neck)-each more than 90%

Alteration in mental status:lethargy-coma-more than 75%

Nausea,vomiting and photophobia

Clinical Presentation

Seizures: 20-40% Focal or generalized Focal seizures:

Infarction Cortical venous thrombosis with hemorrhage Focal edema

Generalized: Anoxia, hyponatremia, drugs Petechial lesions in meningococcal

meningitis.

Diagnosis

When bacterial meningitis is suspected: Obtain blood culture Initiate empirical antimicrobial therapy

The diagnosis is made by examination of CSF

Neuroimaging is needed before LP: H/O head injury, Papilledema, altered level of

consciousness and focal neurological signs

CSF Abnormalities In Bacterial Meningitis

Opening pressure More than 180 mm H2O

White blood cells 1000-100 000 cells/mm3

Glucose <2.2 mmol/l

CSF/serum glucose

<0.4

Protein 100-500mg/dl

Gram stain Positive in >60%

CSF Abnormalities In Bacterial Meningitis

Culture Positive in >80%

Latex agglutination

May be positive in S.Pneumoniae,N.meningitidis,H.influenzae-b ,E.coli and G-B streptococci

Limulus Lysate Detects gram negative meningitis endotoxin

PCR for bacterial DNA

Research test

Diagnosis

MRI: may demonstrate: Cerebral edema Ischemia Meningeal enhacement with gadolinium

Biopsy of petechial skin lesions: Gram stain may reveal meningococci

Differential Diagnosis

Headache, fever, altered consciousness, focal neurological signs and focal or generalized seizures

Periodic lateralized epileptiform discharges (PLEDS)

Lymphocytic pleocytosis with normal sugar Orbitofrontal or medial temporal lobes

changes in MRI.

MENINGOENCEPHALITIS

HERPES SIMPLEX VIRUS ENCEPHALITIS

Differential Diagnosis

Rocky Mountain spotted fever Subdural and epidural empyema, brain

abscess Suharachnoid hemorrhage Chemical meningitis: Rupture of tumor Carcinomatous or lymphomatous meningitis SLE, Sarcoid, Behcet disease

Treatment:Empirical Antibiotics

Preterm infant to infant<1 month

Ampicillin+cefotaxime

Infant 1-3 months Ampicillin+cefotaxime or cefotrixone

Immunocompetent children>3m+adult<55

Cefotaxime or cefotriaxone+vancomycin

Adults>55+alcoholism+debilitating illness

Cefetaxime or ceftriaxone+ampic+vanc

Hosp-acquired, posttrauma, neurosurg

Ampicillin+Vancomycin+ceftazidime

Antibiotics Based on Pathogen

N.meningitides-PEN-S Penicillin G or Ampicillin

N.meningitides-PEN-R Ceftriaxone/ cefotaxime

S.pneumonia-PEN-S Penicillin G

S.pneuomonia-PEN-R Cefotrixone+vancomycin

Gram-negative bacilli Ceftriaxone/ cefotaxime

Psedomonas aeruginosa Ceftazidime

Staphylococci-M-S/R Nafcillin/Vancomycin

Antibiotics Based on Pathogen And Adjunctive Therapy

Listeria monocystogenesis Ampicillin+gentamycin

Haemophilus Influenzae Ceftriaxone/ cefotaxime

Streptococcus agalactiae Penicillin G+Ampicillin

Adjunctive therapy Dexamethasone 10 mg 15-20 min before 1 dose

Increased ICP Elevate head,mannitol hyperventilation

Tuberculosis Meningitis

Clinical Features. Subacute-chronic course with:

low-grade fever, headache, and intermittent nausea and vomiting

followed by more severe headache, neck stiffness, altered sensorium

cranial nerve palsies (usually III, but also II, VII, and VIII) Untreated disease progresses with:

more pronounced meningeal signs, seizures focal neurological deficits, including hemiparesis, increasing drowsiness, and signs of increased ICP

Basal Meningitis

Vasculitis

Diagnosis

Identifying tubercle bacilli on: CSF acid-fast bacilli (AFB) smear or culture establishes

the diagnosis. AFB smear is diagnostic in only 10-30% of cases CSF culture results are positive for M. tuberculosis in 45-

70% of patients but may take 6-8 weeks to become positive.

Because a negative CSF AFB smear result does not rule out TB meningitis and the culture may not yield organisms for weeks, empiric anti-TB therapy can be started as early as possible on the basis of clinical suspicion

Diagnosis: CSF examination

Demonstrates normal or elevated opening pressure Elevated protein (1-5g/L) Low glucose (1.7-2.5 mmol/L) Pleocytosis (averaging 200-400 WBC/mm³ with

lymphocytic predominance). However, patients with miliary TB or CNS

tuberculomas may have a normal CSF initially.

Diagnosis

Investigations should include: general examination for lymphadenopathy and

hepatosplenomegaly Retinal examination for choroidal tubercles chest radiography for lung infection tuberculin test Cranial CT or MRI showing basal meningeal and

sylvian exudates and enhancement with hydrocephalus suggests the diagnosis

Tuberculomas Single or multiple brain or spinal cord lesions Present with signs and symptoms of space-occupying lesions. On CT or MRI scan:

the lesions may be of low or high intensity with ring enhancement Miliary disease is characterized by multiple small (1-2 mm)

lesions. Open or stereotactic biopsy may be necessary if definitive

diagnosis of TB cannot be made at an extraneural site. In regions in which TB is prevalent, the decision to initiate anti-

TB therapy may be made without histological confirmation.

Tuberculomas

Tuberculomas

Spinal Tuberculosis

The most common site of involvement by TB of the spine is in midthorax region.

Back pain is the chief complaint, and paraspinal muscle spasms or kyphotic deformity of the spine (from collapse of vertebra, a gibbus) may be found on examination.

Plain films show: decreased bone density and joint space destruction in long-

standing disease, but may be normal in early disease. Radionuclide bone scanning improves detection of spinal TB, but the best modality is MRI, which simultaneously visualizes the

spinal cord.

Spinal Tuberculosis Progressive paraparesis requires urgent surgical

intervention. Surgery also may be indicated:

for biopsy if the diagnosis is in doubt or to obtain cultures for sensitivities.

The differential diagnosis of vertebral bacterial diseases includes: infections with staphylococci, streptococci and typhoid and other gram-negative bacilli paratyphoid disease brucellosis.

TBM: Management

Isoniazid (INH) 5-10mg/kg (max 300 mg) PO

add pyridoxine,Hepatitis (1-2%), neuropathy (5%), seizures

Rifampin Child 15mg/kg PO, Adult 10mg/kg PO

Hepatitis (1-2%), hypersensitivity

Pyrazinamide 25mg/kg (max 2.5 g/day) PO

Arthralgia (5%), hepatitis (1-5%), hyperuricemia, gout, rash

TBM: Management

Streptomycin Child 30 IM Adult 15mg/kg (max 1 g/day) IM

Hearing loss, vestibular imbalance (1-5%)

Ethambutol 15-25mg/kg (max 2.5 g/day) PO

Optic neuritis

Corticosteroids Severely ill patients

Impending spinal block

Differential diagnosis Untreated or partially treated bacterial meningitis, Other granulomatous meningitides (spirochetes, Brucella, Most fungi Parasites such as Amoeba, Toxoplasma, and trypanosomes), A subacute or chronic granulomatous conditions:

CNS sarcoid lupus Behçet's, granulomatous angiitis

Lymphomatous or carcinomatous meningitis

TBM:MRI

Brucellosis

A zoonosis caused by Brucella species: B. melitensis B. abortus B. suis) Normally a disease of domestic and wild animals Brucellosis is transmitted to humans by ingestion of infected

unpasteurized milk, by aerosol spread, or by contact with infected animals or animal products.

The disease exists worldwide, but is especially prevalent in Mediterranean regions the Middle East, the Indian subcontinent Latin America.

Brucellosis:Acute Febrile Illness

Common symptoms: Chilly sensation, sweats, fever, generalized

malaise Bodyaches in 60% Headache in 50%

Physical signs: Lymphadenopathy, splenomegaly,hepatomegaly Spinal tenderness

Clinical Presentation

Subacute/chronic stages in 15-20% of patients with localized of Bones Joints Lungs Kidneys Liver Lymph nodes and other organs

Nervous Involvement

Is not common Meningitis with cranial nerve palsies Meningoencephalitis Meningomyelitis Optic neuritis Peripheral neuritis Brain Abscess

Cerebrospinal Fluid

Increased opening pressure Lymphocytic pleocytosis: few-several

hundred cells Protein is moderately or greatly increased Sugar content is decreased Elevated immunoglobulins Often contain Brucella agglutinating

antibodies

Neurobrucellosis:Pathology

Subacute meningitis with perivascular infiltrations

Thickening of the vessels in the brain and spinal cord

Degenerative changes in the white and grey matter

Organisms cultured from CSF in few patients

Neurobrucellosis: Diagnosis

History Culture of organism from blood or CSF Positive Brucella agglutination or ELISA test

results with high titers of antibody in blood and CSF

Neurobrucellosis:Treatment

Three-drug therapy with: doxycycline+ an aminoglycoside+ rifampin

for at least 12 weeks. Children under 8 years of age are treated

with trimethoprim/sulfamethoxazole + aminoglycoside +refambin

Adjunctive corticosteroid therapy has been used for concurrent vasculitic or demyelinating disease

LYME DISEASE

Caused by a tick-born spirochaete-Borrelia burgdorferi-Endemic in Europe ands USA

Deer is the natural host for the adult tick The organism can be cultured from brain,

CSF,blood and Skin Pathology:

Meningeal inflammation Perivascular inflammatory cell infiltrate Focal demyelination

LYME DISEASE: Three Stage Course

Initial skin reaction-Erythema chronicum migrans in 60-80% within 3-4 weeks of expoture Myalgia Malaise fever Headache

Erythema chronicum migrans

Neurological Features

Occur in 10-15% of patients Cranial nerve palsies, mainly fifth and

seventh Radiculopathy or myeloradiculopathy Meningitis:CSF lymphocytosis and mild

elevation of protein and oligoclonal bands Encephalitis

Arthritis

Single or multiple joints Remitting and relapsing Diagnosis:

Elevated serum and CSF antibody to B.burgdorferi

Treatment: Severe: IV ceftriaxone Mild: Facial weakness-oral amoxicillin or

doxicyclin

Brain Abscess

Focal infection of the brain Mode of infection:

Infected cotaguous site: ear or sinus Hematogenous: from lungs

Symptoms: Focal signs,fever, headache, neck stiffness Elevated white cell count Diagnosis: MRI or CT scan

Brain Abscess

LP Iis containdicated Treatment:

Surgery Antibiotics

MItronidazole Ceftrixone