An Elusive Case of Tuberculous Meningitis in a Young Man With Altered Mental Status.

BACKGROUND: Tuberculous meningitis (TBM) is a rare, frequently elusive diagnosis, often characterized by vague symptoms and associated with high rates of morbidity and mortality. CASE REPORT: We present a case of TBM in a young man with a headache and altered mental status. In addition, we provide a brief history of TBM, review the pathophysiology of the disease, discuss clinical and radiologic features, and detail the management of TBM both emergently and throughout our patient's hospital course. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our patient's lack of pulmonary symptoms, initially unremarkable head computed tomography, and two prior emergency department evaluations for headache without concerning historical features or physical examination findings collectively highlight the challenges of diagnosing TBM early in its symptom course. We encourage emergency physicians to consider TBM in appropriate patients, particularly those with risk factors for tuberculosis infection.

Stimulation-dependent remodeling of the corticospinal tract requires reactivation of growth-promoting developmental signaling pathways.

The corticospinal tract (CST) can become damaged after spinal cord injury or stroke, resulting in weakness or paralysis. Repair of the damaged CST is limited because mature CST axons fail to regenerate, which is partly because the intrinsic axon growth capacity is downregulated in maturity. Whereas CST axons sprout after injury, this is insufficient to recover lost functions. Chronic motor cortex (MCX) electrical stimulation is a neuromodulatory strategy to promote CST axon sprouting, leading to functional recovery after CST lesion. Here we examine the molecular mechanisms of stimulation-dependent CST axonal sprouting and synapse formation. MCX stimulation rapidly upregulates mTOR and Jak/Stat signaling in the corticospinal system. Chronic stimulation, which leads to CST sprouting and increased CST presynaptic sites, further enhances mTOR and Jak/Stat activity. Importantly, chronic stimulation shifts the equilibrium of the mTOR repressor PTEN to the inactive phosphorylated form suggesting a molecular transition to an axon growth state. We blocked each signaling pathway selectively to determine potential differential contributions to axonal outgrowth and synapse formation. mTOR blockade prevented stimulation-dependent axon sprouting. Surprisingly, Jak/Stat blockade did not abrogate sprouting, but instead prevented the increase in CST presynaptic sites produced by chronic MCX stimulation. Chronic stimulation increased the number of spinal neurons expressing the neural activity marker cFos. Jak/Stat blockade prevented the increase in cFos-expressing neurons after chronic stimulation, confirming an important role for Jak/Stat signaling in activity-dependent CST synapse formation. MCX stimulation is a neuromodulatory repair strategy that reactivates distinct developmentally-regulated signaling pathways for axonal outgrowth and synapse formation.