Contributed by Jason Chiang, MD, PhD and Julia Kofler, MD
The patient was a 27-year-old white male with a history of possible mild mental retardation attributed to traumatic brain injury at the age of 10. He was hospitalized at an outside hospital with several weeks of diffuse lower abdominal pain, mild dizziness and nausea, with approximately 50 pounds weight loss over an uncertain period of time. Four days after admission, he had deteriorating levels of consciousness, requiring intubation for airway protection. He was unresponsive to painful stimuli. Oculocephalic reflexes were absent. He had an upgoing Babinski response bilaterally. EEG showed diffuse generalized slowing. CSF showed 31 RBCs/cu mm, 2 WBCs/cu mm, 96 mg/dl glucose and 58 mg/dl protein. Despite multimodal therapy, the patient's neurologic condition did not improve. Due to a dismal prognosis for neurological recovery, a decision was reached with his family to switch to comfort measures only. The patient passed away 13 days after admission.
RADIOLOGIC AND IMAGING FINDINGS
MRI showed new areas of T2 FLAIR hyperintensity in the posterior pons, thalamus, and bilateral mamillary bodies 4 days after admission. Follow up MRI 7 days after admission showed areas of T2 FLAIR hyperintensity in the frontal cortex, medial thalamus (Fig. 1), hypothalamus, periaqueductal gray matter (Fig. 2), dorsal pons, and inferior cerebellar peduncles.
GROSS NEUROPATHOLOGY FINDINGS
The brain weight is 1495 grams in the fresh state. The dura and leptomeninges are unremarkable. The cerebral hemispheres show no softening, hemorrhages, masses or defects. There is diffuse edema and congestion, but no evidence of herniation is found in the unci or cerebellar tonsils. The vessels of the circle of Willis demonstrate no stenosis or aneurysms.
Coronal sections of the cerebral hemispheres demonstrate uniform thickness of the cortical ribbon with sharp demarcation from the white matter. The white matter shows no discoloration or depression. There is slight enlargement of the ventricular system, with the third ventricle being most prominent. No dilatation of the aqueduct is present. The basal ganglia and thalamus are unremarkable. The hypothalamus appears enlarged. The mamillary bodies show no discoloration. The hippocampus and amygdala are unremarkable.
Sagittal sections of the cerebellum reveal atrophy of the cerebellar vermis. The cerebellar hemispheres appear normal in size and demonstrate unremarkable foliar architecture. Transverse sections of the midbrain demonstrate brown discoloration of the inferior colliculi. The substantia nigra and locus ceruleus are normally pigmented. There is bilateral multifocal brown discoloration of the medullary tectum.
Microscopic examination reveals several circumscribed lesions in the medial thalamus, hypothalamus, mamillary bodies, periaqueductal gray and dorsal tegmentum of the caudal midbrain, inferior colliculi, and floor of the fourth ventricle in pons and medulla. All lesions are morphologically similar in appearance and are characterized by prominent endothelial hypertrophy and proliferation, tissue destruction with accumulation of abundant foamy macrophages, occasional perivascular cuffs of mononuclear inflammatory cells, rare perivascular petechial hemorrhages and rare dystrophic calcifications. Only minimal hemosiderin deposits are noted. Numerous reactive astrocytes are present in a peripheral rim surrounding the lesions. Numerous axonal spheroids are identified within and surrounding the lesions (Figs. 3 & 4).
Representative section of the hypothalamus and mamillary body:
Representative section of the pons:
Immunohistochemical stain for CD68 highlights the accumulated macrophages within the lesions and also widespread microglial activation.
CD68 stain of the hypothalamus and mamillary body:
There is marked reduction in GFAP reactivity within the core of the lesions, consistent with significant loss of astrocytes.
GFAP stain of the hypothalamus and mamillary body:
While there appears to be some neuronal loss in the more central portions, preservation of neuronal cell bodies is seen in the periphery of lesions as highlighted by the NeuN immunostain.
NeuN stain of the hypothalamus and mamillary body:
The axonal spheroids are highlighted by a neurofilament stain.
Neurofilament stain of the hypothalamus and mamillary body: