SummaryNeurospecific biomarkers were elevated in pediatric tuberculous meningitis and showed an increasing temporal profile in patients who died, whereas markers of inflammation decreased in all patients regardless of outcome. Secondary injury mechanisms initiated by inflammation likely cause ongoing brain damage.

Tuberculous meningitis (TBM) is the most severe form of TB with high rates of mortality and morbidity. Here we conduct RNA-sequencing on whole blood as well as on ventricular and lumbar cerebrospinal fluid (CSF) of pediatric patients treated for TBM. Differential transcript expression of TBM cases are compared with healthy controls in whole blood and with non-TB cerebral infection controls in CSF. Whole blood RNA-Seq analysis demonstrates a distinct immune response pattern in TBM, with significant increase in both canonical and non-canonical inflammasome activation and decrease in T-cell activation. In ventricular CSF, a significant enrichment associated with neuronal excitotoxicity and cerebral damage is detected in TBM. Finally, compartmental comparison in TBM indicates that the ventricular profile represents brain injury whereas the lumbar profile represents protein translation and cytokine signaling. Together, transcriptomic analysis shows that disease processes differ between the periphery and the central nervous system, and within brain compartments.

Selective dorsal rhizotomy is a key technique in the surgical management of spasticity in patients with cerebral palsy. The technique evolved from the late 1800s when pioneers like Dana and Abbe performed dorsal rhizotomy in their treatment of refractory pain. These surgeons noted a reduction in muscle tone associated with the operation. When Sherrington then published his Nobel prize-winning work on the corticospinal tract and its role in the neuromuscular system in the 1890s, the course was set for modifying spasticity by aiming surgery at the dorsal roots. This procedure underwent multiple modifications through the next century and today it is, arguably, the most commonly performed operation to treat cerebral palsy children with spasticity. Selective dorsal rhizotomy is a technique that still teaches us a great deal about neurophysiology on a daily basis and it is thanks to the pioneers, described in this article, that we have this tool in our armamentarium.