CNS Infections

• 4 routes by which infections enter the nervous system;
  • Haematogenous spread – most common, generally arterially but less commonly retrograde spread via the venous system
  • Direct implantation – via trauma e.g. lumber puncture
  • Local extension – secondary to an infected air sinus or tooth
  • Through the peripheral nervous system e.g. rabies and herpes

 

• Damage to the nervous tissue can as a consequence of;
  • The infectious agent directly
  • Indirectly via microbial toxins
  • Inflammatory response
  • Immune mediated mechanisms

 

Meningitis

 

• Refers to inflammation of the leptomeninges and the CSF within the subarachnoid space
• As well as infectious meningitis, can also get chemical and malignant
• Infectious meningitis can be classified as;
  • Acute pyogenic
  • Aseptic (viral)
  • Chronic (usually TB, spirochetal or cytococcal)

 

Acute pyogenic meningitis

 

• Causative agent varies with age;
  • Neonates – E.coli and group B strep
  • Elderly – Strep pneumoniae and Listeria monocytogenes
  • Adolescents – Neisseria meningitides. Prevalence of Haemophilis influenzae markedly decreased following the introduction of vaccination
• Clinical signs of meningeal irritation;
  • Photophobia
  • Neck stiffness
  • Headache
  • Irritability
• Cerebrospinal fluid is purulent, with high neutrophils, high protein and low glucose
• Waterhouse-Friderichsen syndrome results from meningitis associated septicaemia with haemorrhagic infarction of the adrenal glands and cutaneous petechiae. It is common with pneumococcal and meningococcal meningitis

 

• In immunosuppressed patients meningitis may be caused by;

·        Klebsiella

·        Anaerobic organisms

 

• Morphology
  • Meningeal vessels are engorged
  • H. influenzae meningitis is generally basal
  • Pneumococcal meningitis is denser around the sagittal sinus
  • Inflammation may extend to the ventricles causing ventriculitis
  • May cause a phlebitis which can cause a venous occlusion and haemorrhagic infarct
  • Leptomeningeal fibrosis and hydrocephalous may develop as a consequence

 

Acute Aseptic (Viral) Meningitis

 

• Less severe than bacterial meningitis
• CSF finding differ – lymphocytic, moderately raised protein level, normal glucose level
• Usually self-limiting
• Generally caused by an enterovirus;
  • Echovirus
  • Coxsackievirus
  • Nonparalytic polio virus
• Morphology
  • No obvious macroscopic changes other than possibly some oedema
  • May be associated with a mild lymphocytic infiltration of the leptomeninges

 

Chronic bacterial meningoencephalitis

 

TB

• Usually present with symptoms of headache, confusion, malaise and vomiting
• Moderate CSF pleocytosis, very elevated protein and glucose either only movderately reduced or normal
• Morphology
  • Subarachnoid space contains a fibrinous exudates, most often at the base of the brain
  • Most common pattern of involvement is a diffuse meningoencephalitis
  • Macrophages, lymphocytes and plasma cells histologically
  • Granuloma formation
  • Arteries running through subarachnoid space may show obliterative endarteritis with inflammatory thickening of the wall and marked intimal thickening
  • Meningitis may be associated with the development of a tuberculoma, a well circumscribed intraparenchymal mass
  • May develop fibrous adhesive arachnoiditis which mat produce hydrocephalus and obliterative endarteritis – brain infarction
  • As the process involves the aubarachnoid space of the spinal cord, nerve roots can be involved as well
• In AIDS patients CNS TB may be associated with less host reaction
• HIV patients are at increase risk of M. avium-intracellulare (may disseminate)

 

Neurosyphilis

• Represents the tertiary stage of syphilis and occurs in 10% of untreated patients
• The 3 major forms are;
  • Meningovascular neurosyphilis
    • Chronic meningitis involving the base of the brain
    • May be associated with obliterative endarteritis and lymphocytic perivascular inflammation
    • Cerebral gummas are plasma cell rich mass lesions which occur in relation to the meninges and can extend into the brain parenchyma
  • Paretic neurosyphilis
    • Treponema pallidum invades the brain causing a progressive loss of mental and physical function terminating in severe dementia (general paresis of the insane)
  • Tabes dorsalis
    • Due to damage of the sensory nerves of the dorsal roots resulting in impaired proprioception and sensory disturbance
    • HIV patients have an increased risk of developing neurosyphilis with an increased rate of progression and severity

 

Neuroborreliosis (Lyme Disease)

• Neurological symptoms include;
  • Aseptic meningitis
  • Facial nerve palsies
  • Mild encephalopathy
  • Polyneuropathies

 

Acute focal suppurative (pus forming) infections

 

Brain Abscess

 

• May arise via;
  • Direct implantation of organisms
  • Extension from adjacent foci
  • Haematogenous spread (primary site usually heart, lungs, distal bones or tooth extraction
• Predisposing factors include;
  • Acute bacterial endocarditis – tends to produce multiple abscesses
  • Cyanotic congenital heart disease – when there is a right to left shunt an loss of pulmonary filtration of organisms
  • Chronic pulmonary sepsis – can be seen in bronchietasis
  • Staph and strep organisms are the most common in immunosuppressed patients
• Morphology
  • Distinct lesions with a necrotic liquefied centre, surrounding fibrous capsule and oedema
  • The most commonly affected areas are the frontal lobe, parietal lobe and cerebellum
  • Microscopically there is lots of granulation tissue with neovascularisation responsible from the oedema
  • Outside the fibrous capsule there is a zone of reactive gliosis
• Patients present with progressive neurological deficits and signs of raised intracranial pressure
• CSF is under pressure, raised WCC and protein level. Glucose in normal
• Abscess rupture can lead to;
  • Ventriculitis
  • Meningitis
  • Venous sinus thrombosis

 

Subdural empyema

 

• Spread from bacterial or fungal infection of the skull bones or air sinuses
• May produce a mass effect
• Thrombophlebitis can develop in the bridging veins that cross the subdural space resulting in infarction
• As well as having focal neurological signs patients may be febrile, have a headache and neck stiffness. If untreated coma can develop
• CSF profile similar to brain abscesses

 

Extradural abscess

 

• Commonly associated with osteomyelitis
• Arises from an adjacent source of infection such as sinusitis or surgical procedure

 

Abscesses differ from empyemas which are collections of pus in pre-existing rather than newly formed body cavities

 

HIV

 

• 60& of AIDS patients develop some neurological dysfunction at some point during the course of their illness

 

HIV Meningoencephalitis

• Manifests are dementia and is referred to as AIDS-dementia complex (ADC)
• Begins with mental slowing, memory loss and mood disturbances and develops with motor abnormalities and bowel/bladder incontinence
• Radiological imaging may show some ventricular enlargement and cortical atrophy
• Morphology
  • Microscopically there is chronic inflammation with widely distributed infiltrates of microglial nodules sometimes with associated tissue necrosis and reactive gliosis
  • Changes occur in the subcortical white matter, diencephalon and brainstem
  • Microglial nodules contain multinucleated giant cells
  • Present in CD4 positive macrophages and microglia
  • Damage to neurones and oligodendrocytes is indirect via cytokine and NO release and alteration of the BBB

 

Vaculoar Myelopathy

• Found in 25% of US AIDS patients
• Occurs in late stage infection
• May be due to indirect cytokine mediated myelin damage
• Slow progression of painless leg weakness, stiffness, sensory loss, imbalance and sphincter dysfunction

 

AIDS associated myopathy and peripheral neuropathy

• Inflammatory myopathy is common and is characterised by a subacute onset of proximal weakness, sometimes pain and elevated CK
• Histologically there is muscle fibre necrosis and phagocytosis, interstitial infiltration with HIV infected macrophages
• An acute, toxic reversible myopathy with ‘ragged red’ fibres and myoglobulinuria may develop in patients treated with zidovudine
• The most common reported peripheral neuropathy problems include, demyelinating polyneuropathy, polyradiculopathy, mononeuritis multiplex
• Histologically there is segmental demyelination, axonal degeneration and epineural and endoneural mononuclear cell infiltration

 

AIDS in children

• In children born with congenital AIDS and untreated clinical manifestations of neurological dysfunction are evident within the first two years of life
• Include a microcephaly with mental retardation and motor developmental delay with limb spasticity
• There is calcification of the large and small vessels of the parenchyma with in the basal ganglia and deep cerebral white matter
• There is also loss in myelin and delay of myelination
• Opportunistic pathogens such as;
  • Toxoplasmosis
  • CMV
  • Progressive multifocal leukoencephalopathy (caused by JC polyomavirus)
  • Infects oligodendrocytes and causes demyelination
  • Crytococcus
  • Are rare in children compared with adults

 

Fungal meningoencephalitis

 

• Primarily encountered by the immunocompromised
• Most often;
  • Candida albicans
  • Mucor
  • Aspergillus fumigatus
  • Crytococcus neoformans
• Three main patterns of fungal infection in the CNS;
  • Chronic meningitis
    • Crytococcal meningitis is becoming increasingly frequent
    • Results in a basal leptomeninges
    • Thickening of the leptomeninges may result in obstruction of CSF flow and a hydrocephalus
  • Vasculitis
  • Parenchymal invasion
    • Abscess formation

 

Protozoal CNS Infection

 

• Cerebral toxoplasmosis is also important in the immunocopromised
• One of the most common causes of neurological disturbance in AIDS patients
• Clinical features evolve over a 1 to 2 week period and may be focal or diffuse
• Radiological studies show ring enhancing lesions
• Morphology
  • Multiple cerebral abscesses
  • Acute lesions consist of central foci of necrosis surrounded by acute and chronic inflammation, macrophage infiltration and vascular proliferation
  • Free tachyzoites and encysted bradyzoites are found in the periphery of the necrotic zone