Saccadic Palsy following Cardiac Surgery: Possible Role of Perineuronal Nets

Abstract

ObjectivePerineuronal nets (PN) form a specialized extracellular matrix around certain highly active neurons within the central nervous system and may help to stabilize synaptic contacts, promote local ion homeostasis, or play a protective role. Within the ocular motor system, excitatory burst neurons and omnipause neurons are highly active cells that generate rapid eye movements – saccades; both groups of neurons contain the calcium-binding protein parvalbumin and are ensheathed by PN. Experimental lesions of excitatory burst neurons and omnipause neurons cause slowing or complete loss of saccades. Selective palsy of saccades in humans is reported following cardiac surgery, but such cases have shown normal brainstem neuroimaging, with only one clinicopathological study that demonstrated paramedian pontine infarction. Our objective was to test the hypothesis that lesions of PN surrounding these brainstem saccade-related neurons may cause saccadic palsy.MethodsTogether with four controls we studied the brain of a patient who had developed a permanent selective saccadic palsy following cardiac surgery and died several years later. Sections of formalin-fixed paraffin-embedded brainstem blocks were applied to double-immunoperoxidase staining of parvalbumin and three different components of PN. Triple immunofluorescence labeling for all PN components served as internal controls. Combined immunostaining of parvalbumin and synaptophysin revealed the presence of synapses.ResultsExcitatory burst neurons and omnipause neurons were preserved and still received synaptic input, but their surrounding PN showed severe loss or fragmentation.InterpretationOur findings support current models and experimental studies of the brainstem saccade-generating neurons and indicate that damage to PN may permanently impair the function of these neurons that the PN ensheathe. How a postulated hypoxic mechanism could selectively damage the PN remains unclear. We propose that the well-studied saccadic eye movement system provides an accessible model to evaluate the role of PN in health and disease.

Functional Magnetic Resonance Imaging (MRI) and MRI Tractography in Progressive Supranuclear Palsy-Like Syndrome

“…This case further attests to the occult nature of this rare and devastating syndrome and perhaps supports Eggers et al's contention 10 that the dysfunction is microscopic in nature. The abnormality detected on T2*-weighted GE imaging may be indicative of microbleeding at the site of midbrain indicating neuronal or axonal injury, 13 but it seems to be only fMRI and MRI Tractography in PSP-Like Syndrome 65 FIGURE 2 fMRI coronal (A), sagittal (B), and axial (C) slices are shown through a location in dorsal anterior cingulate cortex (crosshair).…”

“…Eggers, Horn, and Leigh, article in press). 10 These perineuronal nets are aggregates of chondroitin sulfate proteoglycans that form a supporting lattice-like network around neurons with high firing rates, such as OPNs and EBNs involved in saccadic control. They may have a lower threshold of injury due to ischaemia, and injury to these structures may not be evident on conventional cranial MRI.…”

Post‐Pump Chorea and Progressive Supranuclear Palsy‐Like Syndrome Following Major Cardiac Surgery

“…In terms of PSP‐like syndrome after aortic surgery, there are only a few available pathologic reports. A recent autopsy of a patient who had a PSP‐like syndrome demonstrated fragmentation and severe loss of perineuronal nets surrounding the saccadic burst neurons . Hypoxic damage to the perineuronal nets surrounding the GABAergic projection neurons of the saccadic burst neurons, basal ganglia, and hippocampus may explain the PSP‐like features and frequently accompanied seizure episodes.…”

Clinical Approach to Supranuclear Brainstem Saccadic Gaze Palsies

“…Ischemic injury is considered most likely, given the temporal relationship with cardiac surgery. A recent theory proposes injury to perineural nets that surround brainstem burst neurons ( 51 , 52 ).…”