Case Study 10

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Case Study 10

• Harry Kellermier, M.D.

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Question 1

• The patient is a 27-year-old female with a
  history of complex partial seizures starting at
  age 16.  A typical episode lasts less than one
  minute and consists of her staring blankly ahead
  and occasionally jerking her hand.  She is
  usually disoriented after the episodes.
• An MRI is performed.  What type of MRI sequence
  is this?

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Answer

• T2 FLAIR

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Question 2

• Describe the MRI.

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Answer

• There are multiple subcortical foci of increased
  T2 signal intensity (2 on the left, 1 on the
  right).

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Question 3

• After reviewing additional history on this
  patient, you learn she has a renal tumor, flat,
  brown marks on her skin, and red bumps on her
  nose and cheeks.  What genetic disorder should
  you suspect?

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Answer

• Tuberous sclerosis.  The flat brown marks are
  most likely cafe-au-lait spots, the red bumps on
  her nose and cheeks are facial angiofibromas
  (adenoma sebaceum), and the renal tumor is
  probably an angiomyolipoma.

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Question 4

• The patient then undergoes cortical mapping and
  excision of her epileptogenic focus, yielding the
  following specimen.  What CNS findings are
  associated with tuberous sclerosis?

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Answer

• Tubers, epilepsy, heterotopias, subependymal
  nodules, and subependymal giant cell astrocytoma.

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Question 5

• What are tubers and how do they appear grossly
  and histologically?

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Answer

• Tubers are thought to represent areas of abnormal
  neuronal migration.  Grossly, they appear as firm
  nodules projecting above the surface of the
  brain.  They range in size from millimeters to
  several centimeters and are pale in color.
  Microscopically, the normal cortical architecture
  is disrupted by large, bizarre cells with
  prominent nucleoli.  These cells possess short,
  thick cytoplasmic processes and may exhibit
  single or multiple nucleoli.  Associated with
  these cells is astrogliosis, loss of myelin, and
  occasional calcification.

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Question 6

• What is the name of the characteristic cell found
  in tubers?

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Answer

• Balloon cells.  They express both glial and
  neuronal characteristics.

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Question 7

• Describe the histologic findings.
• Click the following links to view slides HE,
  Vimentin

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Answer

• There is a focus within the subcortical white
  matter showing proliferation of balloon cells and
  gliosis.  Rosenthal fibers are seen.  The
  surrounding white matter also appears gliotic and
  pale.  Subpial gliosis is also noted.  Vimentin
  immunostains highlight the balloon cells and
  reactive astrocytes.

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Question 8

• What is the most commonly affected organ in
  tuberous sclerosis?

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Answer

• The brain.

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Question 9

• What genetic mutations have been linked to
  tuberous sclerosis?

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Answer

• Mutations in the gene encoding the protein
  hamartin at 9p34 and the gene encoding the
  protein tuberin at 16p13.3.

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Question 10

• What are some other systemic manifestations of
  tuberous sclerosis?

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Answer

• Angiomyolipoma, renal cysts, pulmonary
  lymphangioleiomyomatosis, cardiac rhabdomyomas,
  facial angiofibromas, cafe-au-lait spots, ungual
  or subungual fibroms, ash leaf spots, forehead
  plaques, ocular astrocytic hamartomas, colobomas,
  papilledema.

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Question 11

• What is the other name for subpial gliosis
  associated with epilepsy?

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Answer

• Chaslin's gliosis