Parkinsonism and extraocular motor abnormalities with unusual neuropathological findings

Abstract

Parkinsonian patients with ocular motility abnormalities are usually considered to have progressive supranuclear palsy. However, a number of other conditions have been noted to have the combination of parkinsonism and ocular problems. We report a case of rigid akinetic parkinsonism, oculomotor palsy, and eyelid apraxia with postmortem examination. Our findings are unusual in that there was marked gliosis of the substantia nigra with a large amount of free extracellular neuromelanin despite a 3-year clinical course. Only rare hyaline inclusion bodies and no neurofibrillary tangles were seen in the brainstem. Excessive calcification of the vessels of the globus pallidus were also noted. This case represents another example of the diversity of conditions producing parkinsonism with extraocular motor abnormalities.

Progressive supranuclear palsy: neuropathologically based diagnostic clinical criteria.

“…37 Head scanning is an appropriate diagnostic procedure in patients with suspected PSP. The primary utility is to exclude structural lesions that might be contributing to the clinical picture as well as multi-infarct states or hydrocephalus, which have been reported to produce clinical findings similar to PSP.…”

Cellular and Molecular Mediators of Neuroinflammation in the Pathogenesis of Parkinson’s Disease

“…These data suggest that MMP-3 is a crucial mediator released upon damage to dopaminergic neurons and that it activates microglia to further propagate neuronal cell death in PD [42]. Besides MMP-3, damaged or dying dopaminergic neurons release neuromelanin to activate microglia in the SN of patients with PD [62, 63]. Neuromelanin has the potential to be neurotoxic, because excess neuromelanin inhibits the function of dopaminergic neurons, proteasomes and induces the production of toxic factors such as TNF- α , IL-6, and nitric oxide (NO) [64, 65].…”

Human neuromelanin an endogenous microglial activator for dopaminergic neuron death

“…Besides stored in the dopamineric neurons, NM has been found in the extracellular space in the SNpc of PD patients (9). We hypothesized that NM could be released from damaged or dying dopaminergic neurons into the extracellular environment to interact with the surrounding cells, such as remaining dopaminergic neurons and glial cells, including microglia and astroglia.…”