Transcript Case Study 29 - University of Pittsburgh

Case Study 29
Julia Kofler, M.D.
Question 1
A 27 year old male was admitted with several days to
weeks of diffuse lower abdominal pain, dizziness and a
50 pound weight loss over an uncertain period of time.
Shortly after admission, he started to complain of chest
tightness and dyspnea and experienced episodes of
supraventricular tachycardia, ST depression over
precordial leads on EKG and a rise in troponin levels.
The patient also exhibited deteriorating levels of
consciousness and diffuse, generalized slowing on
EEG.
Describe the abnormal findings on the following
representative T2 flair MRI images.
Answer
T2 flair hyperintensities in the medial thalamus, bilaterally,
and periaqueductal gray of the midbrain
Question 2
What is your differential diagnosis?
Answer

Metabolic/toxic process

Infectious/inflammatory process

Ischemic process unlikely given the distribution of the
lesions
Question 3
Despite multimodal therapy, the patient’s neurologic condition did
not improve. He died ~2 weeks after admission following
withdrawal of care.
Gross examination of the brain revealed mild diffuse edema. The
hypothalamus appeared slightly enlarged. Transverse sections
of the brainstem revealed multifocal areas of brown
discoloration. No other gross abnormalities were noted.
Microscopic examination revealed lesions in the mamillary
bodies, hypothalamus, thalamus, periaqueductal gray, inferior
colliculi and subventricular zone of pons and medulla. Describe
the major pathologic features in the following slides of
hypothalamus (including mamillary body) and brainstem at the
transition of midbrain to pons:
Click here to view slide.
Answer
 Circumscribed lesions in the medial hypothalamus,
mamillary body, periaqueductal gray and inferior
colliculi
 Prominent endothelial hypertrophy and capillary
proliferation
 Accumulation of abundant foamy macrophages
 Occasional perivascular cuffs of mononuclear
inflammatory cells
 Rare petechial hemorrhages, hemosiderin deposits
and dystrophic calcifications
Question 4
What are the round eosinophilic structures that can be
seen focally within the lesions (see attached images)?
Answer
Axonal spheroids
Question 5
What is the pathophysiologic process underlying the
development of axonal spheroids? Name a few conditions
where you can see axonal spheroids.
Answer
 Spheroids are axonal swellings due to impaired
anterograde axonal transport
 They are composed of neurofilaments, organelles and
other material that is normally transported along the
axon
 Spheroids are a feature of axonal damage by diverse
insults including trauma and infarcts
 Axonal swellings can also be seen in metabolic
disorders (e.g. Nieman-Pick disease) and nutritional
deficiencies (vitamin E deficiency)
Question 6
Name a few stains which are commonly used to highlight
astrocytes, neurons and axons in tissue sections.
Answer

Astrocytes: Glial fibrillary acid protein (GFAP) stain

Neuronal cell bodies: Nissl stain (Cresyl violet); NeuN
(nuclear reactivity) and neurofilament
immunohistochemical stains

Axons: Neurofilament stain, Silver impregnation
techniques
Question 7
Describe the findings in the following
immunohistochemical stains for GFAP and NeuN?
Click on the following links to view slides:
GFAP; NeuN
Answer

Marked reduction of GFAP reactivity within the core
of the lesions with significant loss of astrocytes

Reactive astrocytes in peripheral rim surrounding the
lesions

Neuronal loss in the more central portions of the
lesions

Preservation of neuronal cell bodies in the peripheral
portions of the lesions

Relative sparing of neurons compared to loss of
astrocytes
Question 8
What is your diagnosis?
Answer
Wernicke’s encephalopathy
Question 9
What is the cause of this disease?
Answer
Thiamine deficiency
Question 10
What are the classical symptoms of Wernicke’s
encephalopathy?
Answer
 Classical triad: Gaze palsies (ophthalmoplegia), ataxia
and confusion/delirium
 Sometimes associated with Korsakoff’s psychosis with
amnesia and confabulations