Cns infections

INFECTIONS 4 routes which infectious agents can enter the CNS

a) hematogenous spreadi) most common

- usually via arterial route- can enter retrogradely (veins)

b) direct implantation

i) most often is traumaticii) iatrogenic (rare) via lumbar punctureiii) congenital (meningomyelocele)

c) local extension (secondary to established infections)

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i) most often from mastoid and frontal sinuses, infected tooth, etc.d) PNS into CNS

i) viruses- rabies- herpes zoster

ACUTE MENINGITIS• Meningitis refers to an inflammatory process of leptomeninges and CSF• Meningoencephalitis refers to inflammation to meninges and brain parenchyma


• Meningitis often associated with infectiona) may be chemical

i) agent introduced into subarachnoid space

• Meningitis classified:a) acute pyogenic

i) usually bacterial meningitisb) aseptic

i) usually acute viral meningitisc) chronic

i) usually TB, spirochetes, cryptococcusd) these types are based on the

inflammatory exudate of CSF


1. Acute Pyogenic (Bacterial) Meningitis• Microorganism vary with age of the patient

a) neonatesi) E. coliii) Strep. pneumoniaiii) Listeria monocytogenes

b) adolescents and young adultsi) Neisseria meningitidis (most common)ii) Haemophilus influenza

- immunizations have markedly reduced this pathogen- most common among infants now is S. pneumoniae


• Clinical S & Sa) systemic signs of infection

superimposed on clinical evidence of meningeal irritation and neurologic impairment

i) headacheii) photophobiaiii) irritabilityiv) neck stiffnessv) nausea, vomitting

b) spinal tab yieldsi) cloudy or frankly purulent CSFii) increased pressureiii) neutrophils


iv) CSF protein concentrationv) markedly glucose

concentrationc) untreated can be fatald) Waterhouse-Friderichsen syndrome

i) results from meningitis-associated septicemia

- hemorrhagic infarction of the adrenal glands

- cutaneous petechiae - common with menigococcal

and pneumococcal meningitis

• In immunosuppressed patients, other pathogens may be involved

a) Klebsiella


2. Acute Aseptic (Viral Meningitis)• Actually a misnomer

a) refers to absence of any recognizable organism

b) generally viralc) clinical course is less fulminant compared to bacterial

• Clinical S & S:a) CSF glucose near normalb) protein only moderately elevatedc) lymphocytic pleocytosisd) usually self limitinge) most common is the enterovirus

i) polio, echovirus, coxsackieviruswww.freelivedoctor.com

f) no distinctive macroscopic characteristics, except

i) brain swellingii) mild, if any, infiltration of the

leptomeninges with lymphocytes• Some class of drugs have been implicated with a true noninfectious meningitis (“drug- induced aseptic meningitis” )

a) NSAIDb) antibioticsc) CSF is steriled) glucose normal (CSF)e) pleocytosis with neutrophilsf) CSF protein


ACUTE FOCAL SUPPURATIVE INFECTIONS

• Brain abscessa) may arise from a variety of routes (see slides # 1 and 2 for details)

i) often from primary infected site in the heart (acute bacterial

endocarditis), lungs, tooth decay, bones

b) Strep and Staph are the most common bacteria

c) cerebral abscesses are destructive lesions


i) central liquefactive necrosis surrounded by fibrous cap

- edema in surrounding area

ii) common sites (in descending order)

- frontal lobe

- parietal lobe

- cerebellum

iii) present with progressive focal deficits

- signs of ICPwww.freelivedoctor.com

- CSF under pressure- WBC and protein - glucose normal

iv) rupture of abscess can cause ventriculitis, meningitis

and venous sinus thrombosisv) surgery and antibiotics have

decreased lethality to less that 10 %• Subdural Empyema

a) bacteria and fungus can spread to subdural space subdural

empyemab) arachnoid and subarachnoid spaces

usually unaffected


c) thrombophlebitis may develop in bridging veins venous

occlusion and infarctd) clinical:

i) febrileii) headacheiii) neck stiffnessiv) untreated may develop

lethargy and comav) CSF profile similar to abscess

• Extradural Abscessa) commonly associated with

osteomyelitisb) usually arise from adjacent site of infection


i) sinusitis or a surgical procedureii) when occurring in spinal

epidural space spinal compression- neurosurgical emergency

CHRONIC BACTERIAL MENINGOENCEPHALITIS

• TBa) headachesb) malaise and confusionc) vomiting


d) CSF: i) moderate pleocytosis

- PMN and MNii) proteins markedly iii) glucose slightly or normal

e) Subarachnoid space fibrous exudate

i) most often at base of brainii) often obliterating the cisternsiii) encasing cranial nerves

f) development of a single intraparenchymal mass

tuberculomai) may cause significant mass

effect


g) clinical:i) most serious is arachnoid

fibrosis and- hydrocepahlus

ii) obliterative endarteritis- arterial occlusion and infarction

iii) spinal cord roots may be involved• Neurosyphilis

a) tertiary stagei) ~ 10% of untreated patients

b) major forms of meningovascular neurosyphilis arei) paretic, and tabes dorsalis


- meningovascular neurosyphilis is chronic meningitis involving base of the brain, spinal leptomeninges and cerebral convexities. Obliterative endarteritis (Heubner arteritis)

- paretic neurosyphilis caused by invasion of the brain by T. pallidum. Progressive loss of mental and physical functions with mood alterations

- Tabes dorsalis is a result of damage by the spirochete to the sensory nerves in dorsal roots, causing locomotor ataxia and sense of position, loss of pain sensation,


• Neuroborreliosis (Lyme disease)a) Borrelia burgdorferib) S & S vary

i) aseptic meningitisii) facial nerve palsiesiii) mild encephalopathyiv) polyneuropathies

VIRAL MENINGOENCEPHALITISVIRAL MENINGOENCEPHALITIS

• Viral encephalitisa) parenchymal infection

i) meningeal inflammation (i.e., meningoencephalitis)


ii) and sometimes spinal cord involvement

(encephalomyelitis)b) most characteristic features

i) perivascular andii) parenchymal mononuclear cell

infiltrationc) intrauterine viral infections may

cause congenital malformationsi) rubella

d) slowly progressive degenerative disease may occur many years

after viral illnessi) postencephalitic parkinsonism

- post WW 1


• Arthropod-borne viral encephalitisa) arboviruses

i) important cause of epidemic encephalitis- especially in tropical regions

b) most important types in Western world are

i) western and eastern equine ii) Venezuelan iii) St. Louisiv) La Crossev) recently in USA, west nile virus


c) Clinical:i) generalized neurologic deficits

- seizures- confusion- delirium- stupor and coma

ii) CSF usually colorless- slightly pressure- initially a neutrophilic pleocytosis, which rapidly- converts to lymphocytes- proteins are - glucose is normal


• HSV type 1 (HSV-1)a) occur at any age

i) most common in children and young adults

b) most common S & S are mood and memory changec) most often begins in the temporal

lobesd) and orbital gyri of frontal lobes

• HSV type 2 (HSV-2)a) in adults as meningitisb) ~ 50% of neonates develop severe encephalitis to mothers having

active primary genital HSV infections


• Varicella-Zoster virus (Herpes Zoster)a) childhood chickenpoxb) reactivation in adults (i.e.,

“shingles”)i) painful vascular skin eruptionsii) usually is self limited, howeveriii) may be a persistent

postherpetic neuralgia syndrome

- ~ 10% of patientsc) overt CNS manifestations are rare

i) however, when present do produce more severe signs

- granulomatous arteritiswww.freelivedoctor.com

• Cytomegalovirusa) occurs in fetuses and immunosupprressed

i) outcome in utero is periventricular necrosis

- severe brain destruction with

later microcephaly and periventricular calcification

b) most common opportunistic viral pathogen in patients with AIDS

i) affects 15-20% of patientsc) localize in paraventricular subependymal regions of the

braini) severe hemorrhagic necrotizing


• Poliomyelitisa) picorra group of enterovirusesb) Clinical:

i) CNS infections manifest with- meningeal irritation- CSF similar to aseptic

meningitisii) with spinal cord involvement,

produces flaccid paralysis- muscle wasting- hyporeflexia in

corresponding portion of the body

- acute affects can cause death by respiratory muscle paralysis


- myocarditis as complicating factor

iii) late neurologic syndrome:- “postpolio syndrome”

develops 25-30 years after initial resolution progressive weakness, decreased muscle mass and pain pathogenesis is unclear• Rabies

a) severe encephalitisb) transmitted to humans via rabid animals


c) Clinical:i) virus enters the CNS in

ascending fashion- along PNS around wound

site- incubation 1-3 months- as infection advances,

patients exhibit extraordinary excitability where

slightest touch is painful. Violent motor

responses seizuresii) contraction of pharyngeal

muscles on swallowing foaming at the mouth aversion to

swallowing, even water (hydrophobia)


iii) Death from respiratory center failure

•HIV/AIDSa) ~ 60% of AIDS patients develop

neurologic dysfunction (see chapt. 6 for details)

b) HIV aseptic meningitis occurs within 1- 2 weeks of seroconversion in ~ 10% of patients

1.HIV meningoencephalitis (subacute encephalitis)

a) remarkable neurologic disorderi) present with dementia (AIDS

dementia complex- - - ADC)


- mental slowing- memory loss- mood disturbances- motor abnormalities (ataxia)- bladder/bowel incontinence- seizures

b) chronic inflammatory reactioni) microglial infiltrates (microglial nodules)

- multinucleated giant cell2.Vacuolar Myelopathy

a) spinal cord disorderi) 20-30 % of AIDS patients in USA


ii) similar to subacute combined degeneration (Vit B12

deficiency) iii) Vit B12 is not changed in

Vacuolar myelopathyiv) pathogenesis unknown

3. Myopathy and Peripheral Neuropathy

a) inflammatory myopathyi) most often described disorder in patients with HIV

- proximal weakness- pain- serum CK


b) most commonly reported syndromes

i) acute and chronic inflammatory demyelinating polyneuropathy

- segmental dymyelination- axonal degeneration

4. AIDS in childrena) microcephaly with mental

retardationb) motor development delay

i) spasticity of limbsc) most frequent abnormality

i) calcification of small and large vessels and parenchyma

within basal ganglia


ii) Delay in myelinationiii) opportunistic infections rare in children with AIDS as

compared with adults.• Progressive Multifocal Leukoencephalopathy

a) PML progressive viral encephalitis caused by:

i) JC polyomavirus- preferentially infects

oligodendrocytes- demyelination is primary

pathologyii) almost always occurs in

immunosuppressed individuals


iii) thought to be from reactivation

of virus as a result of immunosuppression

- ~ 65% of normal people have titers of virus• Subacute Sclerosing Panencephalitis

a) rare progressive diseasei) characterized by cognitive

declineii) spasticity of limbsiii) seizures

b) occurs in children and young adultsi) months or years after initial infection with measles

- altered measles virus


c) myelin degeneration d) viral inclusions (within nuclei) of oligodendrocytes and neuronse) inflammation of white and grey

matter with neurofibrillary tanglesf) with widespread measles

vaccinations, disease nearly has disappeared

(rare cases around world)

FUNGAL MENINGOENCEPHALITISFUNGAL MENINGOENCEPHALITIS

• Encountered primarily in immunosuppressed individuals


a) brain involved late in diseasei) blood borne

b) types:i) Candida albicansii) Mucoriii) Aspergillus fumigatusiv) Cryptococcus neoformans

- chronic meningitis signs- affecting basal

leptomeninges- may obstruct outflow of CSF

• Three major patterns of fungal infectionsa) chronic meningitis


b) vasculitis (thrombosis and infarcts)i) Mucor ii) Aspergillus

c) parenchymal invasioni) granulomas or abscessii) occur with most of the

organismsiii) Candida and Cryptococcus are

most common hereiv) Candida multiple

micro abscesses


OTHER INFECTIOUS DISEASESOTHER INFECTIOUS DISEASES

• Protozoan diseases (review chapter 8 for details)

• Cerebral toxoplasmosis (T. gondii)a) importance since AIDS epidemic

i) one of most common causes of neurologic symptoms- ~ 4 – 30% on autopsy

b) Clinical (subacute in nature):i) evolving over 1-2 weeksii) focal or diffuse


iii) “ring” enhancing lesions- other pathologies also show these lesions. CNS

lymphoma, TB and fungal infections

iv) brain frequently shows multiple abscesses (necrotic lesions)

- cortical areas near white-grey matter junction and deep grey nuclei

- areas of necrosisv) may occur in the fetus (i.e.,

early during pregnancy)www.freelivedoctor.com

• Naegleria sp.a) rapidly fatal necrotizing encephalitis

• Acanthamoeba a) chronic granulomatous meningoencephalitis

PRION DISEASEPRION DISEASE

• Transmissible spongiform encephalitisa) Creutzfeldt-Jacob diseaseb) Gerstmann-Sträussler-Scheinker syndromec) fatal familial insomniad) kuru


• All these disease are associated with an abnormal form of a specific protein

a) prion protein (PrP)i) infectious and transmissible

b) predominantly characterized by spongiform changes.

i) caused by intracellular vacuoles - neurons- glia

c) most patients develop progressive dementia

i) most common clinical picture is Creutzfeldt-Jacob disease


Cns infections

Documents

glucose normal

acute pyogenic

herpes zoster

tabes dorsalis

neck stiffness

obliterative

jacob disease

young adults