CNS Infections, Demyelinating Disorders, and Prion Diseases Flashcards
Meningitis
Inflammation of the pia and arachnoid (leptomeninges).
Inflammation of the dura (pachymeninges) is rare and tends to follow traumatic injury to the skull.
Meningitis is classified into 3 categories based on the type of inflammatory response elicited:
1. Pyogenic meningitis- bacterial
2. Granulomatous meningitis- fungus or TB
3. Lymphocytic meningitis- viral
Bacterial Meningitis
REGARDLESS OF TYPE OF ORGANISM INVOLVED:
the bacterial meningitides share common features:
1. rather sudden onset with fever, severe headaches, stiff neck, clouding of consciousness, and if untreated, often coma and death.
2. a thick yellow, fibrins-purulent exudate over the convexity, or the base of the brain, or both.
3. Congestion fo meningeal vessels, spreading of the inflammatory cells (polymorphonuclear WBC/ neutrophils) along penetrating vessels in the brain tissue, and brain edema.
Exudate accumulates in the same compartment where the CSF circulates.
CSF is important:
1. constitutes a nourishing medium for invading organisms.
2. helps to circulate the organisms around the brain surface and down into the spinal meninges.
3. when withdrawn by lumbar puncture, the fluid yields inflammatory cells and bacteria, allowing correct diagnosis.
Observation of CSF reveals increased protein, increased PMNS, decreased glucose (compared to serum levels because bacteria eat glucose) and increased or normal pressure.
See expanded subarachnoid space, hemorrhage, necrotic tissue; inflammatory cells degranulate as they leave vessels, so they destroy blood vessels=thrombosis=infarction and necrosis.
Macrophages, degranulated protein, hydrocephalus (brain edema).
Untreated meningitis can result in encephalitis: spread infection from meninges (arachnoid, pia, subarachnoid space) to the brain and vice versa.
Neonates: E coli, group B streptococcus
Infants and children: Haemophilus influenzae (vaccine available)
Adolescents and young adults: Neisseria meningitides (meningococcus) (vaccine available)
Adults: Streptococcus pneumoniae, listeria monocytogenes (pneumococcus) (vaccine available).
Route of entry: remains unknown in many cases; a route from the upper nasal passages via the olfactory nerve (through the lamina cribrosa at the base of the skull) has been established for E coli.
Infections converted by droplets, in coughing and sneezing, can gain access to blood stream from the nasopharynx (Neisseria and H. influenzae) or from the lungs (streptococcus pneumoniae).
Granulomatous Meningitis
Characterized fully or to some extent by the cell-mediated immune response share following features:
1. subacute, slowly progressive clinical course with headaches and increasing cranial nerve deficits.
2. the location, at the base of the brain, of a dense whitish thickening of the meninges.
3. formation of granulomatous tissue, comprised of lymphocytes, macrophages, and fibroblasts, with some of the macrophages fused into multinucleated giant cells and others converted into epithelioid cells.
4. Hydrocephalus (dilated ventricles) due to a partial outflow blockage of the CSF by the tissue reaction in the basilar meninges.
TWO WELL KNOWN ORGANISMS CAUSE THIS:
1. Mycobacterium tuberculosis (TB)
2. Cyrptococcal meningitis, a unicellular yeast fungus.
Both are secondary infections with primary focus in the lungs.
Spread to the brain is through blood.
Viral Meningitis
A lymphocytic inflammatory infiltrate of the meninges accompanies all viral encephalitides, but some viruses (ECHO, Coxsackie) elicit a strictly meningeal response.
Enteric (intestinal) viruses reach the meninges via the bloodstream.
Self-limited and do not require treatment.
Clinical signs: headache, anorexia, apathy.
Viruses can be cultured from the CSF.
Most accurate and fastest diagnosis is established by PCR.
Viral encephalitis
They have the proensity to infect different parts of the brain.
Acute viral inflammation of the NS; the tissue is congested and edematous and the cellular reaction consists chiefly of lymphocytes, macrophages, microglial cells and astrocytes.
No pus formed.
Viruses (either RNA or DNA) reach the CNS via the bloodstream or via peripheral nerves (rabies), or a cranial nerve (herpes v. type 1).
Their target is nerve cells (polio virus, rabies virus) or nerve cells and glial cells (herpes v type 1, cytomegalo-virus).
Around infected and dying nerve cells, “glial nodules” form which are a microscopic accumulation of lymphocytes and microglial cells and a re a hallmark of viral infections.
Poliomyelitis
Vaccination available; so not very common anymore.
Reaches the CNS by viremia or by axonal spread (enteric virus) and it attacks and kills motor neurons (bulbar motor nuclei), chiefly of the spinal anterior horns, but also of the cranial nerve nuclei of the medulla oblongata.
Clinically, these acute onset illnesses are called spinal paralytic polio, or bulbar polio.
Respiratory paralysis can be the immediate cause of death.
Survivors have residual paralysis and develop secondary muscle atrophy.
Von Economo’s encephalitis
Effects the midbrain and hypothalamus.
Rabies
Transmitted through the saliva in the bite of a rabid animal.
The virus reaches the CNS via peripheral nerves.
Incubation time is about 4-6 weeks.
The closer the bite is he CNS, the shorter the incubation time.
Neurologic deficits appear acutely and include confusion, hyper irritability, pharyngeal spasm,s leading to hydrophobia (unwillingness to swallow, even water), flaccid paralyses, and coma.
If untreated, death invariably ensues after 1-2 weeks, the cause being respiratory failure.
The viral inflammation is most pronounced in the deep gray matter, brainstem, spinal cord, spinal anterior horns, and spin ganglia.
Some neurons, especially of the hippocampus, reveal cytoplasmic viral inclusion bodies (Negri bodies),
Treatment with vaccine, after an animal bite, should tart before the CNS symptoms begin.
Effects the hippocampus, brainstem, and cerebellum.
Herpes
HSV-1 can gain access to he human brain via the olfactory route and produce sporadic subacute encephalitis.
Clinical findings: fever, changes of mood and behavior, seizures, lethargy, and coma.
Intracranial pressure is increased.
Mortality if untreated is about 75%, treatment with Acyclovir reduces it to 20%.
Can be diagnosed from presence of HSV-1 DNA in the CSF.
Gross findings; unusual for viral disease and could be mistaken for an acute infarction: one or both temporal lobes and inferior parts of the frontal lobes are swollen and softened, with some hemorrhages.
Affected areas are medial part of the temporal and frontal lobes.
Happen in immunosuppressed hosts.
Trigeminal nerve.
Arthropod-borne visruses
Vertebrate hosts and mosquito or tick vectors and human illness occurs in small epidemics.
California virus (La Crossa virus in WI) encephalitis is the most common type in the Midwest.
Easter and Western Equine encephalitis and St. Louis encephalitis.
Clinical signs: patients show irritability, confusion, somnolence (love to sleep), and even stupor or coma.
No specific treatment.
Human Immunodeficiency Virus 1 (HIV-1)
Most due to opportunistic infections, 30% develop subacute dementia (memory loss, apathy, depression), which is based on an invasion of the brain, via bloodstream, of the AIDS virus, HIV-1 itself.
Brain atrophy.
Virus can be cultured from CSF.
Inflammatory infiltrates are located in the white matter, in the deep gray matter, and brain stem.
Associated edema of the white matter, myelin deficiency, and astrogliosis.
Perivascular multinucleate giant macrophages which contain HIV-1 particles.
Progressive multifocal leukoencephalopathy
JC virus; immunosuppressed host
effects the cerebral white matter
Subacute sclerosing panencephalitis
Measles
effects the cerebrum.
Demyelinating Disease of the CNS
Diseases in which there is selective degeneration or destruction of the myelin sheath with relative sparing of the axon.
The disease process primarily involved either the myelin itself or the cells which maintain myelin, oligodendrocytes i the CNS and Schwann Cell’s in the PNS.
Causes of demyelination:
Mechanical: Pressure (mass, lesion, edema)
Nutritional: B12 deficiency, pontine myelinosis, etc.
Toxic: Heavy metal, organophosphate, isoniazid, hexachlorophene poisoning.
Infectious: progressive multifocal leukoencephelopathy
Myelin is white (lipid); white matter is myelinated; stains dark in an H and E stain.
Vascular: subcortical hypoxia of oligodendroglia
Allergic or autoimmune: Experimental allergia encephalomyeities (EAE), multiple sclerosis, Guillain Barre, post exanthematous childhood diseases.
Multiple Sclerosis
Most common and most important of the human demyelinating diseases.
Chronic progressive disease of white matter characterized morphologically by numerous areas of demyelination i the CNS and clinically by a variety of neurologic symptoms and signs which show a tendency towards remissions and exacerbations.
Females affected more than men.
The cause is not known, but most likely to be multifactorial:
1. Immune mechanisms
2. Genetics; 40% susceptibility due to genetics, association with HLA-DR15.
3. Environment
Disease occurs mainly in young adults (20-40), with course varying from 5-25 years.
Prevalence rate is higher in temperate climates than in warmer climates; this data suggests that the causal agent may be more prevalent or more injurious in temperate climates.
Clinical presentation: Classic triad of Charcot: nystagmus (eyes make repetitive, uncontrolled movements), intention tremor (present with purposeful movements), scanning speech.
Symptoms tend to wax and wane and exacerbations of symptoms are often associated with emotional crises.
CSF of MS patients contains elevated levels of oligoclonal IgG immunoglobulins.
Multiple, disseminated, demyelinating lesions in the brain and spinal cord termed “plaques.”
Plaques can be found anywhere in the CNS, but most commonly found in the cerebral white matter surrounding the ventricles (periventricular, often symmetrical- gray patches involving white matter).
Also commonly seen in spinal cord and optic nerves and may extend to gray matter as well although neurons are not primarily affected.
Life expectancy: same as the general public! Given current therapies, most die due to other disease.
Most patients have variable degrees of relapsing-remitting disease: 5-20% have silent MS, 30% have benign MS (shows up once and you don’t relapse).
Lymphocytes T cells, enter by blood stream, spread into white matter, macrophages pick up myelin from axons.
