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INFECTIONS 4 routes which infectious agents can enter the CNSa) hematogenous spreadi) most common- usually via arterial route- can enter retrogradely (veins)b) direct implantationi) 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 CNSi) 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 chemicali) agent introduced into subarachnoid space Meningitis classified:a) acute pyogenic i) usually bacterial meningitisb) aseptici) usually acute viral meningitisc) chronici) usually TB, spirochetes, cryptococcusd) these types are based on the inflammatory exudate of CSF



Acute Pyogenic (Bacterial) MeningitisMicroorganism vary with age of the patienta) neonatesi) E. coliii) Strep. pneumoniaiii) Listeria monocytogenesb) 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, vomittingb) spinal tab yieldsi) cloudy or frankly purulent CSFii) increased pressureiii) neutrophilswww.freelivedoctor.com


iv) CSF protein concentrationv) markedly glucose concentrationc) untreated can be fatald) Waterhouse-Friderichsen syndromei) 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 involveda) Klebsiella www.freelivedoctor.com


2. Acute Aseptic (Viral Meningitis) Actually a misnomera) refers to absence of any recognizable organismb) 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 enterovirusi) polio, echovirus, coxsackievirus



f) no distinctive macroscopic characteristics, excepti) 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, bonesb) Strep and Staph are the most common bacteriac) cerebral abscesses are destructive lesions



i) central liquefactive necrosis surrounded by fibrous cap- edema in surrounding areaii) common sites (in descending order) - frontal lobe- parietal lobe- cerebellumiii) present with progressive focal deficits- signs of ICP



- CSF under pressure- WBC and protein - glucose normaliv) rupture of abscess can cause ventriculitis, meningitis and venous sinus thrombosisv) surgery and antibiotics have decreased lethality to less that 10 % Subdural Empyemaa) bacteria and fungus can spread to subdural space subdural empyemab) arachnoid and subarachnoid spaces usually unaffected www.freelivedoctor.com


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 infectionwww.freelivedoctor.com


i) sinusitis or a surgical procedureii) when occurring in spinal epidural space spinal compression- neurosurgical emergency

CHRONIC BACTERIAL MENINGOENCEPHALITIS

TBa) headachesb) malaise and confusionc) vomitingwww.freelivedoctor.com


d) CSF: i) moderate pleocytosis- PMN and MNii) proteins markedly iii) glucose slightly or normale) Subarachnoid space fibrous exudatei) most often at base of brainii) often obliterating the cisternsiii) encasing cranial nervesf) development of a single intraparenchymal mass tuberculomai) may cause significant mass effect



g) clinical:i) most serious is arachnoid fibrosis and- hydrocepahlusii) obliterative endarteritis- arterial occlusion and infarction iii) spinal cord roots may be involved Neurosyphilis a) tertiary stagei) ~ 10% of untreated patientsb) 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 varyi) aseptic meningitisii) facial nerve palsiesiii) mild encephalopathyiv) polyneuropathies

VIRAL MENINGOENCEPHALITIS

Viral encephalitisa) parenchymal infectioni) meningeal inflammation (i.e., meningoencephalitis) www.freelivedoctor.com


ii) and sometimes spinal cord involvement (encephalomyelitis)b) most characteristic featuresi) perivascular andii) parenchymal mononuclear cell infiltrationc) intrauterine viral infections may cause congenital malformationsi) rubellad) slowly progressive degenerative disease may occur many years after viral illnessi) postencephalitic parkinsonism - post WW 1www.freelivedoctor.com


Arthropod-borne viral encephalitisa) arbovirusesi) important cause of epidemic encephalitis- especially in tropical regionsb) most important types in Western world arei) 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 comaii) CSF usually colorless- slightly pressure- initially a neutrophilic pleocytosis, which rapidly- converts to lymphocytes- proteins are - glucose is normalwww.freelivedoctor.com


HSV type 1 (HSV-1)a) occur at any agei) most common in children and young adultsb) 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 infectionswww.freelivedoctor.com


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 rarei) 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 calcificationb) most common opportunistic viral pathogen in patients with AIDSi) affects 15-20% of patientsc) localize in paraventricular subependymal regions of the braini) severe hemorrhagic necrotizing www.freelivedoctor.com


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 paralysiswww.freelivedoctor.com


- myocarditis as complicating factoriii) late neurologic syndrome:- postpolio syndrome develops 25-30 years after initial resolution progressive weakness, decreased muscle mass and pain pathogenesis is unclear Rabiesa) 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 failureHIV/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 patientsHIV meningoencephalitis (subacute encephalitis)a) remarkable neurologic disorderi) present with dementia (AIDS dementia complex- - - ADC)www.freelivedoctor.com


- mental slowing- memory loss- mood disturbances- motor abnormalities (ataxia)- bladder/bowel incontinence- seizuresb) chronic inflammatory reactioni) microglial infiltrates (microglial nodules)- multinucleated giant cellVacuolar Myelopathya) spinal cord disorderi) 20-30 % of AIDS patients in USAwww.freelivedoctor.com


ii) similar to subacute combined degeneration (Vit B12 deficiency) iii) Vit B12 is not changed in Vacuolar myelopathyiv) pathogenesis unknown3. Myopathy and Peripheral Neuropathya) inflammatory myopathyi) most often described disorder in patients with HIV- proximal weakness- pain- serum CK



b) most commonly reported syndromesi) acute and chronic inflammatory demyelinating polyneuropathy- segmental dymyelination- axonal degeneration4. AIDS in childrena) microcephaly with mental retardationb) motor development delayi) spasticity of limbsc) most frequent abnormalityi) 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 individualswww.freelivedoctor.com


iii) thought to be from reactivation of virus as a result of immunosuppression- ~ 65% of normal people have titers of virus Subacute Sclerosing Panencephalitisa) rare progressive diseasei) characterized by cognitive declineii) spasticity of limbsiii) seizuresb) occurs in children and young adultsi) months or years after initial infection with measles- altered measles viruswww.freelivedoctor.com


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 MENINGOENCEPHALITIS

Encountered primarily in immunosuppressed individuals www.freelivedoctor.com


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) Aspergillusc) parenchymal invasioni) granulomas or abscessii) occur with most of the organismsiii) Candida and Cryptococcus are most common hereiv) Candida multiple micro abscesseswww.freelivedoctor.com


OTHER INFECTIOUS DISEASES

Protozoan diseases (review chapter 8 for details)

Cerebral toxoplasmosis (T. gondii)a) importance since AIDS epidemici) one of most common causes of neurologic symptoms- ~ 4 30% on autopsyb) Clinical (subacute in nature):i) evolving over 1-2 weeksii) focal or diffuse www.freelivedoctor.com


iii) ring enhancing lesions- other pathologies also show these lesions. CNS lymphoma, TB and fungal infectionsiv) 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 DISEASE

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



All these disease are associated with an abnormal form of a specific proteina) prion protein (PrP)i) infectious and transmissibleb) predominantly characterized by spongiform changes.i) caused by intracellular vacuoles - neurons- gliac) most patients develop progressive dementiai) most common clinical picture is Creutzfeldt-Jacob diseasewww.freelivedoctor.com


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