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Central Nervous System Infections

Gbadero D. A.

BUTH

Ogbomoso

Definition

• Infections involving the meningeal coverings of CNS and the CNS parenchyma

Objectives

• Learning about epidemiology of CNS infections

• Understanding causes and basic pathology of CNS infections

• Knowing the features of CNS infection

• Discussing treatment and prevention of CNS infections

Etiological Types

• Viral

• Bacterial

• Fungal

• Parasitic

Clinical types of CNS infections

• Acute

• Chronic

• Meningeal

• Meningoencphalitic

• Encephalitic

• Brain abscess

Epidemiology

• Global in distribution

• All ages involved

• Etiologic agents have predilections for certain ages

• Specific types more common in regional areas

Etiology

• Viral agents include; Enteroviruses responsible mostly for aseptic meningitis. Encephalitis; Herpes viruses, VZV, Mumps, EBV, influenza and Measles

• Bacterial:

• Neonatal - Group B streptococcus, Enterobacteriae, Listeria monocytogenes

• Older children - H. Flu, Neisseria meningitides, Strep pneumonia, Mycobacteria tuberculosis

• Abscesses: S. Aureus, Strep. Pyogenes, H. flu, enteric bacteria and fungi

• Parasites: Plasmodia falciparum

Acute pyogenic meningitis

• Major causative organisms are bacteria;

• Bacteria Gram negative rods E. coli, Klebsiella spp, Pseudomonas spp

• Gram negative bacteria Neisseria meningitides, Haemophilusinfluenza

• Gram positive bacteria; Streptoccocus pneumoniae

Definition

• Inflammation of the leptomeninges (arachnoid and pia mater) caused largely by bacteria and viruses. May occasionally be caused by fungi.

• Aseptic meningitis is the term often used to describe viral meningitis but similar picture may be seen in partially treated bacterial meningitis, Tb, para-meningeal infections e.g brain and epidural abscesses.

Epidemiology

• Worldwide in distribution but found more commonly where infectious bacteria diseases prevalent and among populations where genetic susceptibility play a role

• More commoner among infants

• Congenital immune-deficiencies and CNS malformations

• CSF leaks in basilar fractures

• Common among Sickle Cell Disease patients

Aetiology

• The commonest bacteria causing meningitis in children are:

• Haemophilus influenzae B (Gram negative rods),

• Streptococcus pneumoniae (Gram positive capsulated diplococci),

• Neisseria meningitidis (Gram negative intracellular diplococci).

• Mycobacterium tuberculosis (AFB)

• Viruses:

• Enteroviruses: Herpesviruses – HSV, EBV, VZV

• Arboviruses

• HIV, Mumps virus, Rubella, Measles and Influenza virus

• Fungus – Histoplasma spp

• Parasites Plasmodium falciparum

Pathophysiology

• Microbial from blood can gain access into the CSF by bypassing the blood brain barrier to establish inflammatory response in the leptomeninges

• Bacterial infection cause neutrophils migrations into the CSF

• Bacterial presence reduce the CSF glucose

• Dead neutrophils increase the CSF protein

• Inflammation causes fever and pain

• Inflammation and cerebral oedema may cause irritation, seizures and loss of consciouness

Clinical Features

• The symptoms of meningitis include;

• Abrupt onset of high grade fever

• Petechial rash

• Irritability

• Lethargy, arthralgia, myalgia

• Headache

• Vomiting

• Neck stiffness

• Photophobia

• Seizures

• Diminished sensorium

• Coma

Signs

• Pyrexia

• Photophobia

• Nuchal rigidity

• Bulging anterior fontanel in infants

• Other features of increased ICP include; headache, vomiting and diplopia

• Kernig’s sign

• Brudzinski sign

• Skin rash (meningococcal)

• Variable loss of consciousness and coma

Signs of Raised Intracranial Pressure

• Diplopia

• Ptosis

• Sixth nerve palsy

• Features of raised ICP; Bradycardia, hypertension

• Apnoea suggests RICP with tentoria herniation

• Papilloedema

Meningococcal meningitis

• Caused by Neisseria meningitides

• Gram negative diplodocus

• Affects people of all ages

• Occurs in epidemics in the Africa sub-Saharan region after the harmattan in Nigeria

• The major strains are A, B, C, Y

• May associate with rash and bleeding diathesis

• Vaccine preventable

Strep pneumo meningitis

• Caused by S. pneumonia

• Gram positive streptococcus

• Common cause of meningitis after two years

• Tends to associate with significant complications in childhood

• Vaccine preventable

H. Influenza

• Gram negative cocco-bacillus

• Common cause of meningitis between six months and two years

• Vaccine preventable

Gram negative bacteria

• These include E. coli, Klebsiella spp, Pseudomonas spp., Listeria monocytogenes

• Cause meningitis mostly in the neonatal period and the first three months of life.

• Features of meningitis in the neonates are often more subtle.

• May be present without fever

• Features include; Poor feeding, apnoea, irregular temperatures and jitteriness may be indices of suspicions for meningitis in the neonates.

Other bacterial causes

• Tb

• Bacterial contaminants following traumatic injuries S. aureus, anaerobes,

Diagnosis

• Acute febrile illness associated with seizures and variable loss of consciousness in the presence of signs of meningeal irritation

• Diagnosis is often confirmed by positive CSF tap and culture of Bacteria from the CSF

Differential diagnosis of meningitis

• Cerebral malaria

• Meningo-encephalitis

• Seizure disorder

• Neoplastic disease with Intracranial space occupying lesion

• Sepsis

• Metabolic disorders e.g. Hypoglycaemia

Investigations

• FBC

• E/U

• Malarial rapid diagnostic test

• Malaria smear

• LP and CSF analysis

• Random Blood glucose

• CSF culture

• Blood culture

Lumber Puncture

• Mandatory for diagnosing meningitis and cerebral malaria

• Good assistance necessary

• R/O raised intracranial pressure – papilloedema

• Use appropriate size needles

• Ensure aseptic technique

• Collect samples aseptically in appropriate bottles

Treatment

• IV Ceftriaxone

• IV Cefotaxime

• IV Gentamycin

• IV Crystalline penicillin

• Steroid- IV Dexamethasone

• Anticonvulsant drugs

• Antipyretic analgesic

Supportive therapy

• Admission

• Anti-pyretic drugs and measures

• Anticonvulsant drugs

• Appropriate fluid therapy to prevent SIADHS

• Feeding support

• Prevention of pressure sores

Duration of Treatment

• Four days after complete defervescense

• Seven days for N. meningitides

• Ten days for H. flu

• 14 days for S. pneumoniae

• 21 days for Gram negative enterobactericea

Complications

• SIADHS

• Brain abscess

• Deafness

• Seizures/Epilepsy

• Visual loss

• Paralysis-cerebral palsy

• Mental retardation.

• Microcephaly/Macrocephaly (Hydrocephaly)

Prognosis

• Mortality rate for bacterial meningitis in children remain high despite antibacterial therapy.

• Prognosis worse among neonates and younger infants

• Relapse may occur due to resistant organisms or poor treatment

• Recurrence is rare. May indicate the presence of underlying immunologic or anatomic defect

Prevention

• Immunization

• Chemical prophylaxis

• Avoidance of overcrowding especially during epidemics

• Improved general sanitation and hygiene

• Chemoprophylaxis Rifampicin 10mg/kg/day for three days for contacts of patients with pyogenic meningitis

Microcephalus

• Definition:

• Head circumference measuring more than three SDs below the mean for sex and age

Epidemiology

• Relatively common among mentally retarded population

• Types:

• Primary (genetic) Secondary nongenetic types

Primary Microcephaly

• Primary types No associations with other malformations. Follow Mendelian pattern of inheritance or associated with specific genetic syndrome

• Diagnosis usually made at birth because of small head circumference

Secondary Microcephaly

• Results from a large number of noxious agents that may affect the fetus in utero

• Or in the infants during the period of rapid brain growth especially in the first 2 years of life

Etiology of Primary Microcephalus

• Familial autosomal recessive type

• Autosomal dominant type

• Syndromes: Down syndrome, Edward (trisomy 18)

Secondary Non-genetic etiology

• Radiation

• TORCH infection

• Drugs fetal alcohol, Fetal hydantoin

• Meningitis /encephalitis

• HIE

• Malnutrition

• Hyperthermia

• craniosynostosis

Clinical features

• Small head circumference

• Delay attainment of developmental milestones

• Mental retardation

Investigations

• Serial measurements of head circumference

• Karyotyping

• Serology for TORCH infections

• Measurements of OFC of parents and siblings and compare with standards

• Skull X-rays

• CAT scan and MRI for studying structural anomalies of the brain

Treatment

• Non specific

• Family support for genetic counselling

• Placement child in appropriate programme to address mental retardation

Hydrocephalus

• Definition

• Literally means water-filled cranium

• It can be defined as enlargement of the head over and above that which is expected for the age of the child.

• Hydrocephalus occurs when there is impaired circulation and absorption of CSF or rarely when there is overproduction of CSF by a choroid plexus papilloma

• Hydrocephalus is not a specific disease but rather represents a manifestation of a diverse entities eg

Epidemiology

• Common childhood problems

• 2 per 1000 children

• Common where neonatal infections, prematurity are common

Physiology

• CSF is produces from the choroid plexus of the four ventricles

• About 25% CSF originate from the extra-ventricular sources

• Total volumes varies from 50ml in infants to 150ml in adults

• Lateral ventricles to 3rd ventricle through foramina of Monro

• From 3rd ventricle to 4th ventricle through the aqueduct of Silvius

• From the 4th ventricle into the cisterns at the base of the skull through the midline foramen of Magendie and the lateral foramina of Luschkafrom whence it is distributed into the subarachnoid space

Pathophysiology

• Obstructive or non-communicating hydrocephalus develops from stenosis of the aqueduct or lesions in the 4th ventricle.

• Obstruction may be due to a sex linked recessive trait, NTDs and other congenital malformations

• Neonatal meningitis and subarachnoid hemorrhage may be the cause of non-communicating hydrocephalus in the premature infants

Clinical features

• Macrocephaly

• History of rapidly enlarging head

• Dilated scalp veins

• Wide open and bulging anterior fontanel

• Setting sun eyes

• Brisk reflexes, spasticity, clonus and Babinski sign are common – long tract tracts signs

• Irritability, poor appetite, vomiting, lethargy

• Headache in the older child

• Cracked-pot or Macewen sign indicate separation of sutures

Diagnosis

• Rapidly enlarging head

• Premature birth

• Neonatal meningitis

• Neonatal subarachnoid hemorrhage

• Skull X-ray – separation of sutures

• CT scan and MRI help to identify the specific cause

Differential diagnosis

• Familiar macrocephaly

• SCD

• Rickets

• Neural tubular defects

• Neurofibromatosis

• Osteogenesis imperfecta

Treatment

• Treatment depends or the cause

• Require long term multi-disciplinary management approach

• Medical treatment with Furosemide or Acetazolamide may provide temporal relief

• Most case require surgical intervention by extra-cranial shunts –ventriculo-peritonial shunt

Prognosis

• Long-term prognosis is usually poor

• Developmental disabilities are common

• IQ is usually low

• Visual problems are common