Expounding a Rare Association Between Motor Neuron Disease and Parkinson-Plus Syndromes
Background:
Though it is perceived that motor neuron disease (MND) spares eye movements, certain disease variations may oppose this notion. Development of concurrent MND and Parkinson-plus syndromes (PPS) is a rarely described unitary diagnosis with a likely genetic substrate. We present two such cases suggesting its nonlinear progression.
Results:
The first case is a 64 year old man who developed progressive bulbar speech, right-sided hemiparesis, and strong Babinski signs. Though EMG findings were equivocal, he was managed as MND. He eventually developed vertical gaze palsy, decreased blink rate, masked facies, well as disabling tremors and apraxia. It was thought he had mixed features of PPS. Another case is a 63 year old woman that noted progressive hypophonia, dysphagia, micrographia, bradykinesia, tremors, low mood, and hyperreflexia. It was initially thought to be parkinsonism despite the early bulbar involvement. After limited reponse to carbidopa-levodopa, she was later noted to have slow and restricted vertical saccades, upgaze more than down gaze, spastic dysarthria, and increased axial tone. It was thought to be a progressive supranuclear palsy variant of PPS. When she started exhibiting proximal arm weakness, she was referred for an EMG which showed MND.
Conclusions:
The association between frontotemporal dementia and MND is well documented. The above cases should be evaluated further with medical genetics to determine relevant genes such as MAPT, C9-ORF-72, and progranulin. PPS may have properties of TDP-43 proteinopathy, suggesting a link to MND. Studies show that eye movement abnormalities may be consistent with phosphorylated TDP-43 deposition as it spreads sequentially along corticofugal pathways. These subtle eye movement findings may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in MND.