CASE NUMBER 301

Clinical History, part 1: A 10 year-old child travels with his family on a 4-week “eco-vacation” in Malaysia, backpacking in tropical and semi-tropical forests. They have no direct animal contact, but they are constantly exposed to mosquitos. One day prior to their return to the US, the patient begins to experience headaches, fevers, and chills.

During the transcontinental flight, he becomes increasing disoriented and confused. Upon landing, the family rushes him to a local tertiary medical center. He was obtunded on admission.

Physical Exam findings on admission are as follows:

    • Vitals - Temp 38.4, BP 102/66, P 96, R 20, O2 sats 99%
    • MSK - No icterus, no skin lesions
    • HEENT - No oral lesions, no papilledema
    • Chest - Lungs and heart exams normal
    • Abd - exam normal
    • Neuro – obtunded, withdraws all extremities to pain

Laboratory and imaging results on admission are as follows:

  • MRI of the brain (not shown) reveals diffuse edema but no focal lesions.
  • routine blood labs normal
  • CSF reveals the following:
    • 110 WBCs (70% lymphocytes)
    • 12 RBCs
    • normal glucose and protein.

 

Autopsy slide (courtesy of UIowa)
[DigitalScope]

Clinical History, part 2: Unfortunately, the child never regains consciousness. He develops intractable seizures and hemodynamic instability and dies. Gross and microscopic specimens are evaluated at autopsy.

Image Gallery:

Summary of Gross Findings

The gross findings in viral encephalitis may be underwhelming. The intact brain may show hyperemia (as seen here) due to vascular congestion and edema. Fixed and cut specimens may show punctate hemorrhages in the white matter.

Summary of Microscopic Findings
Acute and subacute encephalitis are characterized by meningeal and perivascular inflammatory infiltrates that are predominantly T cells. In addition, “microglial nodules” composed of small, tight clusters of activated microglia may be seen around dying neurons.
(Review Cerebral Cortex Histology)
Cerebrum
Slide 76
(cerebrum, luxol blue/cresyl violet) [DigitalScope]
Slide 76b (toluidine blue & eosin) [DigitalScope]
  
The cerebral cortex is loosely stratified into layers containing scattered nuclei of both neurons and glial cells.  Examine the layered organization of the cerebral cortex using slide 76 stained with luxol blue/cresyl violet [ORIENTATION] (which stains white matter tracts and cell bodies) or toluidine blue and eosin [ORIENTATION] (TB&E, toluidine blue stains the nuclei and RER of cells whereas eosin stains membranes and axon tracts).  Typically one or more sulci (infoldings) will extend inward from one edge of the section.  Examine the gray matter on each side of the sulcus using first low and then high power.  Neurons of the cerebral cortex are of varying shapes and sizes, but the most obvious are pyramidal cells.  As the name implies, the cell body is shaped somewhat like a pyramid, with a large, branching dendrite extending from the apex of the pyramid toward the cortical surface, and with an axon extending downward from the base of the pyramid.  In addition to pyramidal cells, other nuclei seen in these sections may belong to other neurons or to glial cells also present in the cortex.  You may be able to see subtle differences in the distribution of cell types in rather loosely demarcated layers. There are 6 classically recognized layers of the cortex:

  1. Outer plexiform (molecular) layer: sparse neurons and glia
  2. Outer granular layer: small pyramidal and stellate neurons
  3. Outer pyramidal layer: moderate sized pyramidal neurons (should be able to see these in either luxol blue or TB&E-stained sections)
  4. Inner granular layer: densely packed stellate neurons (usually the numerous processes aren’t visible, but there are lots of nuclei reflecting the cell density)
  5. Ganglionic or inner pyramidal layer: large pyramidal neurons (should be able to see these in either luxol blue or TB&E-stained sections)
  6. Multiform cell layer: mixture of small pyramidal and stellate neurons

Pyramidal cells in layers III and V tend to be larger because their axons contribute to efferent projections that extend to other regions of the CNS –pyramidal neurons in layer V of motor cortices send projections all the way down to motor neurons in the spinal cord!

Deep to the gray matter of the cerebral cortex is the white matter that conveys myelinated fibers between different parts of the cortex and other regions of the CNS. Be sure you identify the white matter in both luxol blue and TB&E-stained sections, as it will appear differently in these two stains. Review the organization of gray and white matter in cerebral cortex vs. spinal cord.

Gross image questions:

  • Describe the gross findings of the brain at autopsy.


VM image questions:

  • Identify an area of the brain on VM that is consistent with the clinical history and gross findings. Take a screenshot and describe what you have identified.


 

Clinical History, part 3: A specimen obtained at autopsy is submitted for immunohistochemical analysis, the results of which are shown below.

Image Gallery:

Summary of Immunohistochemistry Findings
An immunohistochemical stain for West Nile Virus is positive.