Department of Pathology, University of Oklahoma Health Sciences Center

NeuroTest Question #18 Next question Previous question

Answer: D (All of the above) Level of difficulty: 4 NeuroTest NeuroLearn NeuroHelp

Discussion: 

• Pathology: Axonal spheroids are essentially contraction balls of axons. Although axonal spheroids are best demonstrated by silver stains or immunostaining for neurofilament protiens, it can often be seen with hematoxylin-eosin stain. Formation of axonal spheroids as being illustrated here is a salient features in some diseases that are mainly seen in children and young adults. The differential diagnoses in this category include Hallevorden-Spatz disease, neuroaxonal dystrophy (Seitelberger disease), late juvenile, juvenile, and adult onset neuroaxonal dystrophy, neuroaxonal leukodystrophy Nasu-Hakola disease (polycystic lipomembranous osteodysplasia with sclerosing leucoencephalopathy), neuroaxonal dystrophy associated with a deficit in alpha-N-acetyl- galactosaminidase. However, it can also be seen in other pathologic conditions such as diffuse axonal injury, vitamin E deficiency, mitochondrial encephalopathies, areas around stroke, and many other conditions.
• Hallervorden-Spatz disease is a progressive early onset neurodegenerative disease affecting predominantly the motor system. Macroscopically, it is characterized by brown discoloration in the globus pallidus, substantia and red nuclei. On imaging, the globus gives the “eye-of-tiger” sign. Histologically, it is characterized by neuroaxonal dystrophy, neuronal loss and gliosis, and iron deposition in the globus pallidus. Clinicopathologic consideration is necessary for diagnosis in particular for separation from neuroaxonal dystrophy (Seitelberger disease).
• Neuroaxonal dystrophy (Seitelberger disease) is an autosomal recessive disease characterized by widespread axonal spheorids in the CNS and PNS. It has a infantile form and a juvenile form. These spheroids are essentially dystrophic changes involving mainly terminal axons and presynptic terminals. The infantile form begins with pyramidal tract signs. Severe dementia develops later and accompaniies by increasing spasticity that eventually evolves into decorticate rigidity. Seizures are unusual and late. Clinicopathologic consideration is necessary for diagnosis in particular for separation from Hallervorden-Spatz disease. The spheroids are more numerous in the small nerve endings but relative spare in larger branches of peripheral nerves such as sural nerve. Biopsy of skin, muscle, and conjunctiva will have a higher yield than peripheral nerve biopsy.
• Diffuse axonal injury are often seen in head injuries produced by high speed acceleration and deceleration such as those in motor vehicle accidents. [More information on axonal spheroids and diffuse axonal injury]

Comment: KarMing-Fung@ouhsc.edu