Refractory Central Neurogenic Hyperventilation: A Novel Approach Utilizing Mechanical Dead Space.

This report describes the successful management of a case of central neurogenic hyperventilation (CNH) refractory to high dose sedation by increasing the mechanical dead space. A 46-year-old male presented with a history of multiple neurological symptoms. Following an extensive evaluation, he was diagnosed with primary diffuse CNS lymphoma and started on high dose steroids. After initial symptomatic improvement, the patient developed increasing respiratory distress and tachypnea. He was intubated and transferred to the neurointensive care unit (neuro ICU). While in the ICU the patient remained ventilator dependent with significant tachypnea and respiratory alkalosis resistant to fentanyl and propofol. This prompted an attempt to normalize the PaCO2 via an increase of the mechanical dead space. This approach successfully increased PaCO2 and bridged the patient until ongoing therapy for the underlying disease resolved the pervasive breathing pattern typical of CNH. Further investigation is warranted to evaluate this strategy, which upon review of the literature appears underused.

Diverse excitatory and inhibitory synaptic plasticity outcomes in complex horizontal circuits near a functional border of adult neocortex.

The primary somatosensory cortex (SI) is topographically organized into a map of the body. This organization is dynamic, undergoing experience-dependent modifications throughout life. It has been hypothesized that excitatory and inhibitory synaptic plasticity of horizontal intracortical connections contributes to functional reorganization. However, very little is known about synaptic plasticity of these connections; particularly the characteristics of inhibitory synaptic plasticity, its relationship to excitatory synaptic plasticity, and their relationship to the functional organization of the cortex. To investigate this, we located the border between the forepaw and lower jaw representation of SI in vivo, and used whole cell-patch electrophysiology to record post-synaptic excitatory and inhibitory currents in complex horizontal connections in vitro. Connections that remained within the representation (continuous) and those that crossed from one representation to another (discontinuous) were stimulated differentially, allowing us to examine differences associated with the border. To induce synaptic plasticity, tetanic stimulation was applied to either continuous or discontinuous pathways. Tetanic stimulation induced diverse forms of excitatory and inhibitory synaptic plasticity, with LTP dominating for excitation and LTD dominating for inhibition. The border did not restrict plasticity in either case. In contrast, tetanization elicited LTP of monosynaptic inhibitory responses in continuous, but not discontinuous connections. These results demonstrate that continuous and discontinuous pathways are capable of diverse synaptic plasticity responses that are differentially inducible. Furthermore, continuous connections can undergo monosynaptic inhibitory LTP, independent of excitatory drive onto interneurons. Thus, coordinated excitatory and inhibitory synaptic plasticity of horizontal connections are capable of contributing to functional reorganization.

Bidirectional axonal plasticity during reorganization of adult rat primary somatosensory cortex.

Cortical sensory maps contain discrete functional subregions that are separated by borders that restrict tangential activity flow. Interestingly, the functional organization of border regions remains labile in adults, changing in an activity-dependent manner. Here, we investigated if axon remodeling contributes to this reorganization. We located the border between the forepaw and lower jaw representation (forepaw/lower jaw border,(1) FP/LJ border) in SI of adult rats, and used a retrograde axonal tracer (cholera toxin subunit B(2), Ctb) to determine if horizontal axonal projections change after different durations of forelimb denervation or sham-denervation. In sham-denervated animals, neurons close to the border had axonal projections oriented away from the border (axonal bias). Forelimb denervation resulted in a sustained change in border location and a significant reduction in the axonal bias at the original border after 6 weeks of denervation, but not after 4 or 12 weeks. The change in axonal bias was due to an increase in axons that cross the border at 6 weeks, followed by an apparent loss of these axons by 12 weeks. This suggests that bidirectional axonal rearrangements are associated with relatively long durations of reorganization and could contribute transiently to the maintenance of cortical reorganization.