Neuropathology IV Flashcards
what are the causes of CNS infections?
- Bacteria
- Virus
- Fungus
- Parasite
- Prion
what are the routes of entry for CNS infections?
- hematogenous: arterial blood (most common), retrograde anastomoses of face and sinus veins
- direct implantation: trauma or lumbar puncture (iatrogenic; rare)
- local extension: sinusitis, tooth infection, osteomyelitis
- transport along peripheral nerves: rabies, herpes
what are the common bacterial causes of Acute Pyogenic Meningitis in neonates?
Group B Streptococcus
E coli
Listeria Monocytogenes
what are the common bacterial causes of Acute Pyogenic Meningitis in children?
- Neisseria meningitidis ( Associated with Waterhouse-Friedrichsen Syndrome)
- Streptococcus pneumoniae
- Haemophilus Influenzae ( Virtually eliminated due to vaccination)
what are the common bacterial causes of Acute Pyogenic Meningitis in elderly?
Streptococcus pneumoniae
Neisseria meningitidis
E coli
Staph Aureus
Which organisms are commonly associated with meningitis in patients with shunt infections?
Staphylococcus epidermidis and Staphylococcus aureus.
Which organisms commonly cause bacterial meningitis after neurosurgery?
Staphylococcus aureus and Staphylococcus epidermidis
What are the typical organisms causing meningitis in patients with a skull fracture?
Streptococcus pneumoniae and Haemophilus influenzae
what are the clinical features of APM?
Headache
Nuchal rigidity
Clouding of consciousness
Fever (can be absent in up to 50% of cases)
Irritability
how does the CSF change in a patient with acute pyogenic meningitis?
Pleocytosis (neutrophils)
High protein
Low glucose
Bacteria on smear or culture
what are the common viruses that cause acute viral meningitis?
Enterovirus
HSV-2
WNV
What are the typical clinical features of acute viral meningitis?
Symptoms are similar to bacterial meningitis but usually less severe (less fulminant)
What are the typical cerebrospinal fluid (CSF) findings in acute viral meningitis?
- Pleocytosis (mainly lymphocytes)
- Slightly elevated protein
- Normal glucose
- Viral culture or PCR positive
What are the common infectious causes of chronic meningitis?
M. tuberculosis
Cryptococcus
Histoplasma
Coccidioides immitis
Syphilis
What are the characteristic features of CNS tuberculosis (tuberculous meningitis)?
Gross pathology: Greyish, gelatinous, viscous exudate at the base of the brain
CSF findings: Elevated protein, low glucose
What is the most common cause of fungal meningitis, especially in immunocompromised patients?
Cryptococcus neoformans, often acquired from pigeon droppings.
What are the characteristic histologic findings in cryptococcal meningitis?
“Soap bubble” cysts in the brain parenchyma
How is Cryptococcus neoformans visualized in the lab?
Budding yeast seen with India ink or mucicarmine staining
What is the most common cause of a brain abscess?
bacterial infections through direct implantation, local extension (e.g. mastoiditis), and hematogenous spread
What predisposing conditions can lead to brain abscesses via hematogenous spread?
Acute bacterial endocarditis and chronic pulmonary infections (e.g. bronchiectasis)
How might a brain abscess appear on imaging and what condition can it mimic?
As a ring-enhancing lesion, mimicking a brain tumor
What is the typical pathological appearance of a brain abscess?
A discrete destructive lesion with central necrosis surrounded by granulation/fibrous tissue
What symptoms are typically seen with brain abscess due to increased intracranial pressure?
Progressive focal neurological deficits and general signs like headache, nausea, and vomiting and very high mortality rate
What is the preferred specimen for microbiological diagnosis in brain abscess and what is the treatment?
Direct culture of the drained abscess (not CSF)
Surgery plus antibiotics
What are the common viral causes of encephalitis?
Arbovirus (e.g., West Nile virus)
Enterovirus
Herpes Simplex Virus (HSV)
Epstein-Barr Virus (EBV)
Cytomegalovirus (CMV)
Mumps virus
JC virus
Which viruses commonly affect the CNS
and what areas in encephalitis?
- Temporal lobe – HSV I/II
- Brainstem – West Nile Virus (WNV), Rabies
- Spinal cord – Polio, West Nile Virus (WNV)
What are the key gross and microscopic pathological findings in encephalitis?
- Gross: Edema, Congestion, Hemorrhage, Herniation (in severe cases)
- Microscopy: Microglial nodules, Neuronophagia, Perivascular lymphocytic infiltrate, Viral inclusions
Which protozoa are known to cause CNS infections?
Toxoplasma
Naegleria (Amebiasis)
Acanthamoeba
Malaria
Which metazoan parasites can cause CNS infections?
Cysticercosis
Echinococcus
Which Rickettsial infections can affect the CNS?
Typhus
Rocky Mountain Spotted Fever
What are the ways immunocompromised patients are infected with CNS toxoplasmosis?
undercooked meat or exposure to cat feces often seen in AIDS patients
What are the microscopic features of CNS toxoplasmosis (Toxoplasma gondii)?
- Necrotizing brain lesions with surrounding inflammation
- Fibrinoid vascular necrosis (damage to blood vessel walls)
- Few or no lymphocytes
- Tachyzoites: indicate active infection
- Bradyzoites: encysted form, usually at the edges of abscesses
How is CNS toxoplasmosis diagnosed and what are key differentials?
Diagnosis confirmed by immunohistochemistry (IHC) for Toxoplasma gondii
Differential diagnoses include:
* Trypanosoma cruzi (identical-appearing cysts)
* Histoplasma capsulatum (small yeasts, GMS stain +, IHC for toxoplasma is negative)
What causes Progressive Multifocal Leukoencephalopathy (PML), and who is most at risk?
- demyelinating disorder of the CNS caused by reactivation of the latent JC virus (JCV), primarily affecting immunocompromised individuals (AIDS) and in patients receiving immunosuppressive therapies like Natalizumab
** only JCV is known to cause CNS disease
What are the clinical symptoms of Progressive Multifocal Leukoencephalopathy (PML)?
Sensory deficits
Hemianopsia (loss of half of the visual field)
Cognitive dysfunction
Aphasia (language difficulties)
Gait disturbance
Seizures (less common)
What imaging findings are characteristic of Progressive Multifocal Leukoencephalopathy (PML)?
multifocal white matter lesions predominantly in subcortical cerebral white matter and cerebellar peduncles, along with gray matter lesions in the basal ganglia and thalamus
What are the macroscopic features seen in Progressive Multifocal Leukoencephalopathy (PML)?
small ovoid, yellow-tan foci of discoloration that are most prominent near the cortical gray-white matter junction
What are the key microscopic findings in Progressive Multifocal Leukoencephalopathy (PML)?
demyelination, loss of oligodendrocytes, and nuclear inclusions in oligodendrocytes. Virally infected cells often stain positive for Ki-67 and p53, and there are cytologically bizarre, enlarged astrocytes.
how is Progressive Multifocal Leukoencephalopathy (PML) mainly diagnosed?
through PCR by testing the CSF for JC virus DNA or through
- Immunohistochemistry (IHC)
- Electron Microscopy (EM)
- In situ hybridization
What is Cysticercosis?
infection caused by Taenia solium (pig tapeworm) that forms single or multiple cysts in the brain parenchyma, ventricles, or subarachnoid space
- minimal inflammation while the parasite is alive
- calcification of the cysts occurs after the parasites death due to inflammation
What are some diagnostic tools used to identify demyelinating conditions?
Diagnosis is based on clinical history, neurological exam, cerebrospinal fluid (CSF) analysis, neuroimaging, and neurophysiological studies
what are the diseases associated with demyelination?
Multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis (ADEM), ANHEM, PML, CPM, Guillain-Barré Syndrome
What is Multiple Sclerosis and what causes it?
most common autoimmune demyelinating disease of the CNS that is caused by an immune response, primarily involving helper T cells attacking myelin antigens, leading to demyelination with axonal preservation.
Who is most affected by MS and what are common symptoms?
affects women more than men (M:F = 1:2), between ages 20–50 and presents with motor, sensory, and cognitive symptoms, often with optic neuritis and a relapsing-remitting course.
What are the key diagnostic findings for MS?
- MRI: Periventricular/subcortical white matter lesions separated in time and space
- CSF: Mildly elevated protein, pleocytosis, and oligoclonal IgG bands
What are potential contributing factors to MS development?
exact cause is unknown, but factors include autoimmunity, genetics (HLA-DR association), infections, and possible neurodegenerative processes
What is Neuromyelitis Optica (NMO), and how is it different from Multiple Sclerosis?
also called Devic disease, is an autoimmune demyelinating disorder characterized by bilateral optic neuritis and spinal cord demyelination
- has a distinct pathophysiology and epidemiology, more common in Asian women and associated with antibodies against aquaporin-4
- It features perivascular inflammation rich in eosinophils and neutrophils but has fewer T cells compared to MS
What is the role of aquaporin-4 antibodies in NMO?
antibodies target aquaporin-4 channels on astrocytes and the antibodies are found in 60–90% of patients and are considered a key diagnostic marker, helping differentiate NMO from MS.
What are the key features of Acute Disseminated Encephalomyelitis (ADEM)?
post-infectious, autoimmune demyelinating disease that usually follows a viral infection and affects the entire brain diffusely, often causing perivenous demyelination in deeper cortex and grey matter
** prognosis is variable, ranging from full recovery to death
What makes Acute Hemorrhagic Leukoencephalitis (AHLE) more severe than ADEM?
a fulminant variant of ADEM that progresses rapidly, often following a respiratory infection, more common in children and young adults
- Lesions show widespread necrosis and hemorrhage (e.g., perivascular ball and ring hemorrhages), and the outcome can be fatal or result in complete recovery
What is Central Pontine Myelinolysis (CPM) and what typically causes it?
osmotic demyelination, is an acute demyelinating disorder affecting the basis pontis and parts of the pontine tegmentum most often occuring 2–6 days after the rapid correction of hyponatremia
- damage is due to osmolality shifts harming oligodendrocytes, there is no inflammation, and neurons and axons remain preserved
What is Guillain-Barré Syndrome (GBS)?
T-cell mediated acute demyelinating polyneuropathy, often preceded by a viral infection which presents with progressive muscle weakness and mild sensory loss
what does the CSF and microscopy show for Guillain-Barré Syndrome (GBS)?
- CSF analysis shows elevated protein without pleocytosis (albuminocytologic dissociation)
- Microscopically, there is demyelination with infiltration by endoneural lymphocytes and macrophages
