CNS infections (1 of 2)

CNS infections (1 of 2)

How can microbes enter the nervous system? Hematogenous the most common mostly arterial can be from facial veins (through anastomoses with venous sinuses of the skull) Direct implantation penetrating (open) trauma lumbar puncture, surgery etc. congenital problems such as myelomeningocele Local extension from infected sinuses (most common: mastoid, frontal), teeth, skull, or vertebrae Some viruses can be transported through peripheral nervous system rabies herpes zoster

Bacterial infections Meningitis Localized infections Acute pyogenic Chronic May be also caused by fungi Meningitis = inflammation of leptomeninges and subarachnoid space mostly due to infection but may be: chemical meningitis Abscess mostly bacterial but can be also caused by fungi or parasites Subdural empyema rarely can be caused by fungi Meningoencephalitis = meningitis + inflammation of brain parenchyma

Bacterial acute pyogenic meningitis *Systemic signs of infection *Headache, photophobia, phonophobia, irritability, clouding of consciousness Symptoms/signs of meningeal irritation *Klebsiella and anaerobes more in immunosuppressed atypical clinical course and CSF findings *Neck stiffness *In spinal tap (lumbar puncture): -Cloudy/purulent (too many neutrophils) CSF -Increased pressure -As many as 90,000 neutrophils per cubic millimeter -Increased protein concentration -Markedly reduced glucose content -Bacteria may be seen on a smear or may be cultured sometimes a few hours before the neutrophils appear

Bacterial acute pyogenic meningitis, cmplications Severe involvement of leptomeningeal veins (phlebitis) may lead to venous occlusion and hemorrhagic infarction of the underlying brain Extension into brain substance focal cerebritis sometimes formation of abscess Extension into ventricles ventriculitis Waterhouse-Friderichsen syndrome adrenal hemorrhage due to meningococcal meningitis-associated septicemia (along with petechial rash) also with pneumococcus

Bacterial acute pyogenic meningitis, morphology Elsevier. Kumar et al. Robbins and Cotran pathologic basis of diseases 9 th **On microscopic examination: *Neutrophils may fill the entire subarachnoid space or, in less severe cases, may be confined to regions adjacent to leptomeningeal blood vessels *In untreated meningitis, Gram stain reveals varying numbers of the causative organism

Viral infections Meningitis Encephalitis Brainstem and spinal cord syndromes Acute aseptic Encephalitis (not arthropod-borne) Arthropodborne encephalitis Rhombencephalitis Spinal poliomyelitis Of viral infections, we will only discuss this in this lecture other viral pathologies will be discussed in the next lecture

Acute aseptic (viral) meningitis Aseptic is a clinical term that means: No organisms in bacterial culture are found in a patient with a picture of meningitis also meningeal irritation, fever, and alterations of consciousness but less fulminant than pyogenic meningitis self-limited Viral etiology (in about 80% of cases enteroviruses), but may be bacterial, rickettsial, or autoimmune in origin

Acute aseptic (viral) meningitis, cont d CSF finding are different from pyogenic meningitis: the pleocytosis (increased WBC count) here is lymphocytic not neutrophilic the protein elevation is only moderate the glucose content is nearly always normal Viral aseptic meningitides are usually selflimited and are treated symptomatically On microscopic examination, there is either no recognizable abnormality or a mild to moderate leptomeningeal lymphocytic infiltrate

Aseptic meningitis-like picture due to chemical irritant or rupture of epidermoid cyst into subarachnoid space (chemical meningitis) No organisms isolated (sterile CSF) Neutrophils May be increased protein Normal glucose

Chronic meningitis Mainly: mycobacteria, some spirochetes, and fungi may also involve the brain parenchyma Tuberculous meningitis *General symptoms: headache, malaise, mental confusion, and vomiting *Moderate increase in WBCs (mononuclear or mononuclear + polymorphonuclear) *Protein is markedly high *Glucose is moderately reduced or normal *May cause a well-defined mass (= tuberculoma) *May cause arachnoid fibrosis hydrocephalus Spirochetal infection *Neuroberreliosis *Neurosyphilis tertiary (occurs in 10% of the untreated) more and more severe in AIDS 3 patterns (isolated or in combination) Meningovascular neurosyphilis obliterative endarteritis base of brain Paretic neurosyphilis progressive parenchymal loss and increased microglial cells loss of mental and physical functions psychiatric problems eventually severe dementia Fungal meningitis see next slide Remember: -sensory ataxia positive Romberg test Stamping gait Tabes dorsalis damage to the sensory nerves in the dorsal roots impaired joint position sense and ataxia loss of pain sense skin & joint damage (Charcot joints) lightning pains absence of deep tendon reflexes

Fungal meningitis Especially in immunocompromised can be associated with high fatality Cryptococcus neoformans Histoplasma capsulatum Coccidioides immitis

Parenchymal infections Brain abscess Viral encephalitis will be discussed in the next lecture Fungal encephalitis Parasitic encephalitis

Brain abscess Check http://www.radiologyassistant.nl/en/p47f86aa182b3a/brain-tumor-systematic-approach.html for references Mostly bacterial Of the predisposing conditions: -Acute bacterial endocarditis, from which septic emboli are released multiple abscesses -cyanotic congenital heart disease right-to-left shunt and loss of pulmonary filtration of organisms -chronic pulmonary infections, as in bronchiectasis Elsevier. Kumar et al. Robbins basic pathology 10th Discrete destructive lesion with liquefactive necrosis surrounded by granulation tissue/fibrosis outside: gliosis

Brain abscess, clinical manifestations Like a tumor: focal neurological deficit and increased intracranial pressure CSF white blood cell count and protein may be elevated However, lumbar puncture has little role in the diagnosis of brain abscess since organisms are more reliably cultured by draining the abscess directly A systemic or local source of infection may or may not be apparent Abscess rupture can lead to ventriculitis, meningitis, and venous sinus thrombosis If untreated, progressive and can result in fatal herniation

Fungal encephalitis Usually granulomas or abscesses, often with meningitis Candida albicans multiple microabscesses, with or without granulomas Mucormycosis infection of nose/sinuses in diabetics with ketoacidosis is a risk Aspergillus fumigatus widespread septic hemorrhagic infarctions because of its marked predilection for blood vessel wall invasion with subsequent thrombosis

Parasitic parenchymal infections Cerebral toxoplasmosis (by Toxoplasma gondii): Check https://emedicine.medscape.com/article/229969-overview for references...modified -immunosuppressed adults or neonates (transplacentally) triad of chorioretinitis, hydrocephalus, and intracranial calcifications Tachyzoites -inflammation and breakdown of the blood-brain barrier at sites of infection imaging studies often show edema associated with ringenhancing lesions Giemsa Check https://www.cdc.gov/dpdx/toxoplasmosis/index.html for references...modified -abscesses, frequently multiple, most often involving the cerebral cortex (near the gray-white junction) and deep gray nuclei -both free tachyzoites and encysted bradyzoites may be found at the periphery of the necrotic foci Bradyzoites in cyst

Parasitic parenchymal infections, cont d Cysticercosis: -It is the consequence of an end-stage infection by the tapeworm Tenia solium -Cysticercosis typically manifests as a mass lesion and can cause seizures. Symptoms can intensify when the encysted organism dies, as occurs after therapy Amebiasis -Naegleria species rapidly fatal necrotizing encephalitis -Acanthamoeba chronic granulomatous meningoencephalitis