Exam 2: [CNS Infectious Diseases] Flashcards
Routes by which Infection can get into the CNS
1) Haematogenous (Bacteremia, Virema)
2) Directly from Local Infection
3) Penetrating injuries (Cribiform Plate or Ear Fractures provide pathway to the cranium)
Primary Infections of the MENINGES [CNS] List
1) Acute Bacterial (suppurative meningitis)
2) Acute Viral Meningitis
3) Chronic Meningitis: tuberculosis, cryptococcidiosis
Acute Bacterial (Suppurative) Meningitis : Site of Infection, Components Increased/Decreased:
- Infection is in Leptomeningitis
- CSF shows increased pressure
- Contains: organisms, increased protein decreased glucose, neutrophils (pus) so CSF looks cloudy
- Type of organism varies depending on pt. Age
Acute Bacterial (Suppurative) Meningitis: Organisms in Different Age Groups
Neonates/Infants: group B strep, E. Coli, Listeria
6 mo-5yrs (FORMER): H. Influenzae strain B
6 mo-5yrs (CURRENT): Streptococcus pneumonia
5yrs-Young Adult: Neisseria Meningitidis
Older Adults: S. Pneumoniae & Gram Negatives
Acute Bacterial (Suppurative) Meningitis: Pathology
- Meninges Congested & Inflamed
- Neutrophils & Fibrin Present
- Bacteria are Obvious on CSF Smear
- Culture Gives Sensitivities
Acute Bacterial (Suppurative) Meningitis: Clinical Features
- Fever, Headaches, Stiff Neck, Altered Mental Status, Kernig’s Sign, Brudzinski’s Sign
- May have symptoms of the previous infection
Acute Bacterial (Suppurative) Meningitis: Treatment & Progression
- Progresses Very Rapidly
- Medical Emergency
- Prognosis related to rapidity of treatment
What should be suspected from an adult who was previously well and may resent as part of an epidemic?
N. Meningitidis
Acute Bacterial (Suppurative) Meningitis: Complications
1) Epilepsy, Hydrocephalus, Neuro Deficits (mental retardation, CN palsies of CNII & CNVIII, spinal nerve neuropathies)
2) Significant Mortality Rate
Meningococcus Complications
1) DIC (Disseminated Intravascular Coagulation) abnormal blood clotting
2) Septic Shock
3) Waterhouse-Friedrichsen Syndrome
Neurosyphilis: Caused by what Organism, Symptoms occur when? Infiltrate & what + Test?
- Cause by organism Treponema Pallidum
- Symptoms may occur years after infection
- 2/3 yrs after infection Meninges have Lymphocytic Infiltrate and a (+) VDRL Test (cure=penicillin)
When does Meningovascular Syphillis Occur?
- 3 Years following infection
- Chronic inflammation of meninges -> cranial nerve palsies
- Some cases have “Gummas” that act as space-occupying lesions
Neurosyphillis: After 10 years
- “Parenchymous Syphillis” at this Stage
- General Paresis (dementia & paralysis)
- Tabes Dorsalis
What Symptoms does Tabis Dorsalis Have?
- In spinal cord (lightning pains, sensory loss, hypotonia, areflexia)
- Argyll-Robinson Pupils
- Charcots Joints
What Does General Paresis show?
Progressive dementia & psychosis with cerebral atrophy
Causative Agents of Viral Meningitis
1) Coxsackievirus B
2) Mumps
3) EBV
4) Echovirus
Viral Meningitis Features
- Produces Aseptic Meningitis (No Bacteria)
- Benign, Self-Limiting
- May spread to Encephalitis
- CSF is clear
- Cells = Lymphocytes
- Protein moderately raised, Glucose is Normal
Chronic Meningitis Causative Agents
1) Mycobacterium Tuberculosis
2) Cryptococcus
3) Brucella Species
4) Treponema Pallidum
Meningeal Appearance in Chronic Meningitis
- Thick Meninges (all 3)
- Fibrinous Exudate in the Subarachnoid Space
Chronic Meningitis Leads To:
Fibrous Adhesions Causing Obstructive Hydrocephalus
Chronic Meningitis Cellular Components
[In CSF]
- Increased # of Mononuclear Cells
- Increased Protein
- Decreased Glucose
Chronic Meningitis: Signs/Symptoms & Prognosis
- Insidious Onset & Less Marked than in the Acute Forms
- Poor Prognosis
Different Ways Viruses can Affect the Brain
- From Systemic Infection
- Direct Target of the Brain
- Specific areas of Brain OR All-Over
- Specifically target Neurons
- Specifically Target Neuroglia
- Healthy OR Immunocompromised Individuals
Viral Encephaltis: Pathological Features
- Perivascular Cuffing of Mononuclear Cells
(Lymphocytes, plasma cells, monocytes) - Microglial Nodules often Present
- Neuronophagia if Neuron has Dies
- Inclusion Bodies in Neurons
Viral Encephalitis: Prognosis
Very Serious Condition that can lead to Death or Permanent Neurological Defects
Arbovirus Infections
1) St. Louis Encephalitis
2) Eastern Equine Encephalitis
3) Venezuelan Encephalitis
4) California Encephalitis
5) West Nile Encephalitis
Sporadic Viral Infections
1) Herpes Simplex Encephalitis
2) Cytomegalovirus
3) Progressive Multifocal Leukoencephalopathy
4) Subacute Sclerosing Panencephalitis (SSPE)
Epidemic Viral Infections
1) Arbovirus Infections
2) HIV Encephalitis
St Louis Encephalitis: Vector/Reservoir, Time of Year, Population at Risk
Vector: Mosquito
Reservoir: Birds (including Poultry)
Late Summer & Early Fall
Very Young & Elderly @ Highest Risk
St. Louis Encephalitis: Histology
- Perivascular Infiltrates
- Glial Nodules [Brain Stem]
St. Louis Encephalitis: Clinical Signs/Symptoms
- Fever, Photophobia, Meningism
- Consiousness Disurbances, Convulsions
- Focal Neurological Signs & Symptoms
**In fatal cases: Body temp keeps rising, patient goes into a coma, then dies
HIV Encephalitis (AIDS- dementia or HIV Encephalitis): % that Show changes, Change in HIV-1, What does it produce?
- 90% show changes at autopsy
- 60% show neurological changes
- In HIV-1, Brain shows Atrophy
- Produces Progressive Neurological Disease
HIV Encephalitis (AIDS- dementia or HIV Encephalitis): Histology
- Perivascular Infiltrates
- Glial Nodules
- Multinucleated Giant Cells
- Changes most obvious in (White Matter & Basal Ganglia)
Herpes Simplex Encephalitis: MC type in Adults & Neonates
Adults: HSV-1 Infection
Neonates: HSV-2
Herpes Simplex Encephalitis: Produced Pathologies, MC Location & Treatment
- Produces: Hemorrhagic Necrotizing Encephalitis
- MC Location: Temporal Lobes & Frontal Orbital Areas
- Treatment: Acyclovir (reduces mortality)
Herpes Simplex Encephalitis: Histology
- Perivascular Infiltrates
- Glial Nodules
- Inclusion bodies in the nuclei of affected Neurons
Cytomegalovirus Encephalitis: Population Affected & Area of the Brain Affected)
- Neonates & Immunocompromised Individuals
- Affects Ependyma (may affect any brain area)
Cytomegalovirus Encephalitis: Histology
- Perivascular Infiltrates
- Glial Nodules
- Enlarged Neurons with obvious Intranuclear Inclusions
Progressive Multifocal Leukoencephalopathy: Population Affected & Produced Pathologies
- AIDS or Immunocompromised Individuals
- Acute, rapidly progressive illness with Multifocal Cerebral Dysfunction
Progressive Multifocal Leukoencephalopathy: Cause & Tissue Affected
- Cause: JC Virus (in the papovavirus group)
- Affects Oligodendrocytes Production in areas of Demyelination
What are the Acute Disseminated Encephalomyelitis Diseases? (Definition)
Monophasic Demyelinating Disease that follows a Viral Illness or in Immunization for a Virus
Acute Disseminated Encephalomyelitis: Preceding Viruses
1) Measles
2) Chicken Pox
3) Rubella
Acute Disseminated Encephalomyelitis: Preceding Immunizations
1) Smallpox
2) Rabies
3) Pertussis
Acute Disseminated Encephalomyelitis: Symptoms
- Occur 1 week following illness
- Longer if following an Immunization
Subacute Sclerosing Panencephalitis: Definition
Slowly progressing Dementia that Occurs a few years after a child has had Measles
(Chronic Measles Infection)
Subacute Sclerosing Panencephalitis: Histology
- Degeneration (Brain) Gray Matter & Basal Ganglia
- Intranuclear Inclusions seen in Infected Cells
Subacute Sclerosing Panencephalitis: Symptoms
- Personality Changes
- Myoclonic Type Movements
- Death in 1-2 Years
Poliomyelitis: Etiological Agent Transmission
(Poliovirus) that is transmitted by the fecal-oral route
Poliomyelitis: Internal Pathological Pathway
- Multiplies in Lymphoid Tissues of Oropharynx & Intestine for 2 Weeks
- Then goes into Blood Stream & Causes Flu-Like Illness
- Virus then gets into the Meninges producing Acute Lymphocytic Meningitis
Poliomyelitis: Cells Affected
[In small % of Individuals]
- Involves the Lower Motor Neurons in the Anterior Horn
- Motor Nuclei of the Medulla
Poliomyelitis: How is the Spinal Cord Affected?
Spinal Cord: Asymmetric and Flaccid Paralysis with Muscle Atrophy & Loss of Deep Tendon Reflexes
Poliomyelitis: How is the Medulla Affected?
Can be involvement of the muscles for Respiration producing Problems with Ventilation
Poliomyelitis: Long-Term Effects
- Surviving patients have varying degrees of Paralysis
- Some required assisted Ventilation
- Post-Polio Syndrome in Long-Term Survivors
Polio Immunizations
Injected vaccine > Oral Vaccine
[due to issues of Polio Infections caused by the Oral Vaccine
Rabies: Definition, Prognosis, Incubation Period
Definition: Viral disease (rare in humans) but common in animals, both Wild & Domestic
Prognosis: Death is inevitable (no treatment)
Incubation: 1-6 months depending on site of bite
How does Rabies enter the body?
Enters the Cutaneous Nerve Radicals at the site of Innoculation & travels to the CNS
Rabies: Causes what?
Severe, Necrotizing Encephalitis
Rabies affects what areas of the Brain?
1) Brain Stem
2) Basal Ganglia
3) Hippocampus
Rabies: Dx & Clinical Features
Dx: Negri Body
Clinical: Fever, generalized Convulsios precipitated by Sensory Stimulation
Rabies: Prevention
1) Controlling Disease in Animal population
2) Vaccination of Dogs & Cats
3) Antirabies Vaccine (humans) immediately after exposure
Prion Encephalopathies (Spongiform Encephalopathies): General facts
**”Proteinaceous Infectious Particles”
- “slow virus disease”
- Produced ONLY by Protein Agents
- Similar Diseases:
1) Scrapie in Sheep
2) Mad Cow in Cows
Prion Encephalopathies (Spongiform Encephalopathies): Histology
1) Progressive Neuronal Loss
2) Demyelination
3) Spongiform change in cerebral White Matter
Prion Encephalopathies (Spongiform Encephalopathies): 2 Major Diseases
1) Creutzfeld-Jakob Disease
2) Kuru
Prion Encephalopathies (Spongiform Encephalopathies): Clinical Features
Dementia followed by Ataxia followed slowly by Death (No Treatment Known)
Prion Encephalopathies (Spongiform Encephalopathies): Transmission Risks
1) Through Handling Tissues
(Disease is resistant to Formalin)
2) By Corneal Transplant
3) Pituitary Growth Hormone Extract
Demyelinating Congenital Diseases of the CNS
1) Metachromatic Leukodystrophy
2) Adrenoleukodystrophy
Demyelinating Acquired Diseases of the CNS
1) Multiple Sclerosis
2) Acute Disseminated Encephalomyelitis
Demyelinating Congenital Diseases of the CNS: Features
1) Intrinsic disorder interferes with maintenance of Myelin
2) Genetic Defects
3) Manifests in Early Childhood
4) Progresses Relentlessly
5) Widespread/Symmetric loss of Myelin
6) Brain usually Atrophic
Metachromatic Leukodystrophy: Inheritance & What is it?
- Autosomal Recessive
- Abnormal gene on Chromosome 22
- Accumulation of Sulfate containing Lipids
Metachromatic Leukodystrophy: Symptoms of Late Infantile & Late Juvenile Form
- Motor Symptoms
- Progressive Disability that leads to Death 5-10 years from Onset of Condition
Metachromatic Leukodystrophy: Microscopy Features
- Demyelination with Gliosis
- Metachromatic with Toluidine Blue
Adrenoleukodystrophy: Different Forms
[many with different inheritance]
- Some Autosomal recessive
- Some X-Linked Recessive (MC)
Adrenoleukodystrophy: Presentation & Progression
Presentation:
Early school years with Neurological symptoms & Adrenal Deficiency
Progression:
Rapid & Fatal
What is a Defining Characteristic of Adrenoleukodystrophy?
Very-Long-Chain-Fatty-Acids
(Why it affects myelin is unknown)
Multiple Sclerosis: MC What? Characteristic Lesion/ How many lesions & what they produce?
1) MC Aquired Demyelinating CNS Disease
2) Characteristic Lesion=Plaque of Demyelination
3) Multiple CNS Lesions producing focal neurological signs/symptoms
Multiple Sclerosis: Geographical Distribution
- MC in climates close to Equator
- Scandinavia being the Highest
- Northern Europe 2nd
- Lowest in the Tropics
Multiple Sclerosis: Etiology
Unknown
Multiple Sclerosis: Associations
- Familial Distribution
- HLA-DR2 Antigens
- (Postulated) is associated w/ Measles
Multiple Sclerosis: Risk
If a person moves from high-risk to low-risk area under the age of 15 (low-risk)
If a person moves after the age of 15 ( high-risk)
Multiple Sclerosis: Immune Factors
1) Perivascular cuffing of Lymphocytes & Macrophages found in Plaques
2) CDa4+ and CD8+ (cytotoxic) Lymphocytes found in plaques that are destructive to Myelin In-Vitro
3) CSF has increased Gamma Globulins which show increased antibody production int he CNS
Multiple Sclerosis: Incidence
1) 1:1000 of the population
2) Onset is 20-40 years (any age possible)
3) Earlier the onset = Worse the Disease is
4) 2:1 Female
Multiple Sclerosis: Pathology
1) Plaques of Demyelination
2) Proliferation of Astrocytes
3) Oligodendrocytes are lost
Multiple Sclerosis: Clinical Features
- Chronic w/ Exacerbations & Remissions
- Lesions occur anywhere, but Optic Neuritis is most common (Unilateral Vision Loss)
Multiple Sclerosis: Where does it Affect?
Cerebellum, Spinal Cord, Brainstem
(random distribution)
Multiple Sclerosis: Produces what?
Multitude of neurological deficits over the course of many years
Acute Disseminated Encephalomyelitis: Pathology
- Small Foci of Demyelination of White Matter (Brain & Spinal Cord)
- Lymphocytic Infiltration
- Lymphocytes that react against Myelin-Basic-Protein are present
Acute Disseminated Encephalomyelitis: Clinical Features
- Headache, lethargy & Coma
(After initial infection or immunization)
Acute Disseminated Encephalomyelitis: Prognosis
- 20% Mortality rate
- Survivors recover slowly over next few months
- Many have permanent neurological Deficits
When does Meningovascular Syphilis Occur? Infection Location and What does it eventually produce?
3 Years following infection
Chronic Inflammation involving Meninges -> Producing Cranial nerve Palsies
Other term for Poliomyelitis
Picornaviridae-RNA
Parasitic Infections
1) Toxoplasmosis
- Toxoplasma gondii
2) Primary Amoebic Memingocephalopathy
- Naegleria Fowleri (brain-eating amoeba)
Brain Abscess: Cause & Location
Cause: Blood borne pathogens, Local sinus infections, or direct trauma
Location: Frontal (sinus), Temporal (ear), Parietal (blood)
Brain Abcess: Internal Reprocusions
- Liquefactive Necrosis within days
- Increased ICP
- Ventricular Seeding, Tonsilar Herniation
Brain Abscess: Prognosis
100% Fatal without Excision and Chemo
Pernicious Anemia: What is it?
- Autoimmune (chronic atrophic gastritis)
- Leads to lack of intrinsic factor
- Leads to decreased B12 absorption
Pernicious Anemia: Megaloblastic Macrocytic Anemia
Subacute combined Degeneration of spinal cord due to demyelination of both tracts
(Sensory & motor)
Alzheimer Disease: Features
- Beta-Amyloid Plaques
- Neuritic (senile) Plaques
- Granulovascuolar Degeneration
- Neurofibrillary Tangle
- Neuronal Loss
- Lipofusion
- Astrogliosis
Huntington’s Disease: What is it?
Enlargement of the Frontal Horns of the Lateral Ventricles of the Brain
Tay-Sachs Disease
** Cherry red spot in Macula of Eye
- Caused by Deficiency in Beta hexosaminidase A (HEX A)
- Baloon swelling of Nerve Cells
Niemann-Pick Disease: Features
Kayser-Fleischer Rings (in the eye iris)
Wernicke-Korsakoff Syndrome: Features
- Thiamin (B1) deficiency
- Alcohol Abuse
- Change in Mental Status
- Ophthalmoplegia
Phenylketonuria
- Musty Body Odor
Phenylalanine -> (PAH) -> Tyrosine
NADH -> (DHPR) -> NAD
Tetrahydrobiopterin -> (PAH) -> Dihydrobiopterin
Dihydrobiopterin -> (DHPR) -> Tetrahydrobiopterin
Tuberculous Meningitis: Transmission & Bacteria
- Droplet Inhalation -> Lungs -> Lymph Nodes
- Mycobacterium Tuberculosis Bacilli
CNS TB: Froms
1) Tuberculous Meningitis
2) Intracranial Tuberculoma
3) Spinal Tuberculous Arachnoiditis
Mycobacterium Tuberculosis Bacilli form:
- Small Subpial/Supependymal Foci of Metastatic Caseous Lesions
- Progression: Foci enlarge & rupture into subarachnoid space resulting in Meningitis
Fungal Encephalitis: Migration Route
Into Parenchyma of brain through BBB
Fungal Encephalitis: Fungal Species most Pathogenic to Humans
Cryptococcus Neoformas
Spinocerebellar Degeneration: General Information
- Absense of voluntary muscle control (cerebellum)
- Autosomal Dominant
- Gene Affected: AXTN1
Spinocerebral Degeneration: Friedreich Ataxia: Areas Affected, Symptoms, What Protein is Affected?
- Spinal Cord, Peripheral nerves, Cerebellum & Heart
- Muscle weakness & Ataxia, balance/coordination
- Protein: Frataxin (diminished energy for cells)
(Iron builds up in the mitochondria)
Amyotrophic Lateral Sclerosis (ALS): Pathological Features
- Loss of PYRAMIDAL BETZ CELLS in Ventral Horns of Spinal Cord (motor nuclei & motor cortex)
- Axonal swelling containing disarrayed neurofillaments
Wilson Disease: What is it, Mode of Inheritance & Gene mutated:
- Copper accumulation in the hepatocytes (basal ganglia, cornea & kidneys) -> increased iron
- Autosomal Recessive
- ATP7B Mutation (copper transporting ATPase)
Hepatic Encephalopathy: Definition
Neurocognitive Abnormalities that occur in patients with Acute or Chronic Liver Disease or Portosystemic Shunting
Gene AXTN1 does:
Provides instructions for making Ataxin-1 protein
Amyotrophic Lateral Sclerosis (ALS): Intracellular Aggregates
- Ubiquinated Inclusions
- Bubina bodies
- Hyaline Conglomerate
Amyotrophic Lateral Sclerosis (ALS): CNS cells activated
Microglia & Astrocytes
Amyotrophic Lateral Sclerosis (ALS): Genes Associated & Gene Function
1) TDP-43
2) FUS
(Function in DNA/RNA processing mechanisms)
Hepatic Encephalopathy: Histologic Hallmark
Alzheimer Type II astrocyte: enlarged, pale nuclei with rim of chromatin
Hepatic Encephalopathy: Lab findings
Elevated Blood Ammonia
Hepatic Encephalopathy: Epidemiology
- Chronic Alcoholism
- Acute drop poisoning
- Hepatic failure
- Post Portosystemic Bypass
Hepatic Encephalopathy: Pathological Cells Found
1) Ammonia
2) Inflammatory Cytokines
3) Manganese Deposition in Basal ganglia
4) GABA
5) Microbiota
6) Aromatic Amino Acids
Acute Hepatic Encephalopathy: Cause
Brain edema caused by swelling of Perivascular Astrocytes
Hepatic Encephalopathy: CNS Tissues Affected
1) Globes Pallidus
2) Putamen
3) Pons
4) Thalamus
5)Dentate Nucleus
6) Cortical GRAY MATTER (Deep Layers)
Concussion: Pathological Features
- Bruising/ Swelling of the Brain
- Tearing of Blood Vessels
- Injury to Nerves
Concussion: Physical Signs
1) Loss of Conciousness
2) Balance Impairment
3) Behavior Changes
4) Slow Reaction Times
5) Sleep Disturbances
Concussion: Symptoms
Somatic: Headache, Dizziness
Cognitive: “In a Fog”
Emotional: Labillity (unstable)
At what point does Post-Concussion Syndrome Occur?
When Symptoms persist for longer than 7-10 Days
Tertiary Neurosyphilis: Clinical Features
- Gummatous Lesions (Soft Granuloma usually in the liver)
- Exclusively Neuro Symptoms
- Develops 10-25 years after infection
Tertiary Neurosyphilis: Organs Affected
- Brain Nerves
- Eyes
- Heart & Blood Vessels
- Liver
- Bones & Joints
List of Cerebrovascular Diseases
1) Cerebral Vascular Accidents
2) Global/Regional Ischemic Infarction
3) Subarachnoid/Intracerebral Hemorrhage
4) Aneurysm
5) AV Malformations
List of MC [Meningitis] Infections of the Nervous System
1) Bacterial / Suppurative
2) Neurosyphilis
3) Granulomatous (Tuberculosis)
4) Viral
List of MC [Encephalitis] Infections of the Nervous System
1) Fungal
2) Viral
3) St. Louis
4) HIV
5) Herpes Simplex
6) Progressive Multifocal Leukoencephalopathy
7) Subacute Sclerosing Panencephalitis (SSPE)
8) Prion Encephalopathies
List of Nervous System Demyelinating Disorders
1) MLD
2) MS
3) ALD
4) PML
5) Post Infectious Encephalomyelitis
6) Pernicious Anemia
List of Inherited Metabolic Nervous System Disorders
1) Phenylketonuria
2) Tay-Sachs
3) Niemann-Pick
4) Wilson
List of Acquired Metabolic Nervous System Diseases
1) Wernicke-Korsakoff
2) Hepatic Encephalopathy
3) Subacute Combined Degen. of the Spinal Cord
Tuberculosis may produce
Granuloma on the Meningeal Surfaces
